Original Article
Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet
Tempol melhora o perfil lipídico e previne a hipertrofia ventricular esquerda em camundongos nocaute para o gene do receptor de LDL (LDL-/-) sob uma dieta hiperlipídica
Lido
7284
Vezesque se leu este artigo
1986
Total PDF
5298
Total HTML
Compartilhar estatísticas
array:26 [ "pii" => "S0870255117305450" "issn" => "08702551" "doi" => "10.1016/j.repc.2017.02.014" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1040" "copyright" => "Sociedade Portuguesa de Cardiologia" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2017;36:629-38" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3403 "formatos" => array:3 [ "EPUB" => 171 "HTML" => 2711 "PDF" => 521 ] ] "Traduccion" => array:1 [ "en" => array:20 [ "pii" => "S2174204917302416" "issn" => "21742049" "doi" => "10.1016/j.repce.2017.02.014" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1040" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2017;36:629-38" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2621 "formatos" => array:3 [ "EPUB" => 133 "HTML" => 2170 "PDF" => 318 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "629" "paginaFinal" => "638" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Tempol melhora o perfil lipídico e previne a hipertrofia ventricular esquerda em camundongos nocaute para o gene do receptor de LDL (LDL-/-) sob uma dieta hiperlipídica" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1419 "Ancho" => 1573 "Tamanyo" => 66169 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Blood levels of low-density lipoprotein in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; LDL: low-density lipoprotein; SC: standard chow; SC+T: standard chow + Tempol. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Igor Cândido Viana Gonçalves, Cláudio Daniel Cerdeira, Eduardo Poletti Camara, José Antônio Dias Garcia, Maísa Ribeiro Pereira Lima Brigagão, Roberta Bessa Veloso Silva, Gérsika Bitencourt dos Santos" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Igor Cândido" "apellidos" => "Viana Gonçalves" ] 1 => array:2 [ "nombre" => "Cláudio Daniel" "apellidos" => "Cerdeira" ] 2 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Poletti Camara" ] 3 => array:2 [ "nombre" => "José Antônio" "apellidos" => "Dias Garcia" ] 4 => array:2 [ "nombre" => "Maísa" "apellidos" => "Ribeiro Pereira Lima Brigagão" ] 5 => array:2 [ "nombre" => "Roberta" "apellidos" => "Bessa Veloso Silva" ] 6 => array:2 [ "nombre" => "Gérsika" "apellidos" => "Bitencourt dos Santos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255117305450" "doi" => "10.1016/j.repc.2017.02.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305450?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302416?idApp=UINPBA00004E" "url" => "/21742049/0000003600000009/v1_201709220127/S2174204917302416/v1_201709220127/en/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S0870255117305486" "issn" => "08702551" "doi" => "10.1016/j.repc.2017.07.003" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1042" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2017;36:639-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1803 "formatos" => array:3 [ "EPUB" => 184 "HTML" => 1230 "PDF" => 389 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Therapeutic strategies targeting oxidative stress to improve dyslipidemia and left ventricular hypertrophy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "639" "paginaFinal" => "640" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estratégias terapêuticas dirigidas ao <span class="elsevierStyleItalic">stress</span> oxidativo para melhoria da dislipidemia e da hipertrofia ventricular esquerda" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1247 "Ancho" => 1583 "Tamanyo" => 193059 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Proposed mechanisms to explain the improvement of dyslipidemia and left ventricular hypertrophy by Tempol, a superoxide dismutase mimetic, in agreement with Gonçalves et al.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> NO: nitric oxide; NOS: nitric oxide synthase; ROS: reactive oxygen species; SOD: superoxide dismutase.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Flávio Reis" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Flávio" "apellidos" => "Reis" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204917302428" "doi" => "10.1016/j.repce.2017.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302428?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305486?idApp=UINPBA00004E" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255117305486/v1_201709150927/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S0870255117305462" "issn" => "08702551" "doi" => "10.1016/j.repc.2017.07.002" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1041" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2017;36:627-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2682 "formatos" => array:3 [ "EPUB" => 142 "HTML" => 2065 "PDF" => 475 ] ] "pt" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Comentário Editorial</span>" "titulo" => "Inotrópicos na abordagem da insuficiência cardíaca aguda e sua repercussão renal – serão todos iguais?" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "627" "paginaFinal" => "628" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Inotropes for the management of acute heart failure and their renal repercussions: Are they all the same?" ] ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Inês Rangel" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Inês" "apellidos" => "Rangel" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204917302337" "doi" => "10.1016/j.repce.2017.08.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302337?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305462?idApp=UINPBA00004E" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255117305462/v1_201709150927/pt/main.assets" ] "asociados" => array:1 [ 0 => array:20 [ "pii" => "S0870255117305486" "issn" => "08702551" "doi" => "10.1016/j.repc.2017.07.003" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "1042" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "dis" "cita" => "Rev Port Cardiol. 2017;36:639-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1803 "formatos" => array:3 [ "EPUB" => 184 "HTML" => 1230 "PDF" => 389 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Therapeutic strategies targeting oxidative stress to improve dyslipidemia and left ventricular hypertrophy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "639" "paginaFinal" => "640" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estratégias terapêuticas dirigidas ao <span class="elsevierStyleItalic">stress</span> oxidativo para melhoria da dislipidemia e da hipertrofia ventricular esquerda" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1247 "Ancho" => 1583 "Tamanyo" => 193059 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Proposed mechanisms to explain the improvement of dyslipidemia and left ventricular hypertrophy by Tempol, a superoxide dismutase mimetic, in agreement with Gonçalves et al.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> NO: nitric oxide; NOS: nitric oxide synthase; ROS: reactive oxygen species; SOD: superoxide dismutase.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Flávio Reis" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Flávio" "apellidos" => "Reis" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2174204917302428" "doi" => "10.1016/j.repce.2017.09.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204917302428?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305486?idApp=UINPBA00004E" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255117305486/v1_201709150927/en/main.assets" ] ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Tempol improves lipid profile and prevents left ventricular hypertrophy in LDL receptor gene knockout (LDLr-/-) mice on a high-fat diet" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "629" "paginaFinal" => "638" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Igor Cândido Viana Gonçalves, Cláudio Daniel Cerdeira, Eduardo Poletti Camara, José Antônio Dias Garcia, Maísa Ribeiro Pereira Lima Brigagão, Roberta Bessa Veloso Silva, Gérsika Bitencourt dos Santos" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Igor Cândido" "apellidos" => "Viana Gonçalves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Cláudio Daniel" "apellidos" => "Cerdeira" "email" => array:1 [ 0 => "daniel.cerdeira.84@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Eduardo" "apellidos" => "Poletti Camara" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "José Antônio" "apellidos" => "Dias Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Maísa" "apellidos" => "Ribeiro Pereira Lima Brigagão" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Roberta" "apellidos" => "Bessa Veloso Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Gérsika" "apellidos" => "Bitencourt dos Santos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Faculdade de Medicina, Universidade José do Rosário Vellano (UNIFENAS), Alfenas, MG, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Bioquímica (DBq), Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas, MG, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Tempol melhora o perfil lipídico e previne a hipertrofia ventricular esquerda em camundongos nocaute para o gene do receptor de LDL (LDL-/-) sob uma dieta hiperlipídica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1419 "Ancho" => 1573 "Tamanyo" => 66169 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Blood levels of low-density lipoprotein in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; LDL: low-density lipoprotein; SC: standard chow; SC+T: standard chow + Tempol. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiovascular disease is the leading cause of morbidity and mortality and is responsible for approximately 30% of all deaths, claiming approximately 17 million lives per year worldwide in 2012.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">1–3</span></a> Furthermore, many studies have firmly established the relationship between cardiovascular disease and metabolic disorders and underlying conditions such as dyslipidemia, diabetes, and hypertension.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">4–8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Dyslipidemia and associated atherosclerotic/cardiovascular events can present with intense inflammation and increased production of reactive oxygen/nitrogen species (ROS/RNS) from mitochondrial oxidative stress and/or the NADPH oxidase complex, which can cause oxidative modification of LDL, thus amplifying the inflammatory potential (i.e., recruitment of phagocytes and activation of the neutrophil oxidase [Nox]-2 system) and proatherogenic events. Moreover, uncontrolled dyslipidemia can have serious consequences for the cardiovascular system, resulting in morphological changes (left ventricular hypertrophy [LVH]), dysfunction, and even heart failure.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">9–16</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Regulation of lipid metabolism is an important target for therapeutic intervention in dyslipidemic processes to prevent or reduce the risk or severity of cardiovascular disease, and appropriate intervention can have an impact on its clinical course. However, due to the high cost, prolonged use, and especially the adverse effects associated with some lipid-lowering drugs, a drug to control dyslipidemia that presents fewer side effects and a better cost/benefit ratio is highly desirable.<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">17–19</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Studies have explored other compounds with antioxidant properties in the prevention of cardiovascular disease.<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">10,20</span></a> Over the last few decades, nitroxides have been widely investigated because of their antioxidant capabilities.<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">20–22</span></a> Among them, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) is a superoxide dismutase (SOD) mimetic that shows a good partition coefficient, interacts with a broad spectrum of oxidants produced in the human body, and is able to break the chain of redox reactions.<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">21,23,24</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">It has been shown that Tempol has radioprotective, chemopreventive, hypoglycemic, antihypertensive, antineoplastic, and cardioprotective effects, as well as protecting against ischemia-reperfusion injury. It also prevents obesity and neurodegenerative diseases and attenuates renal dysfunction and oxidative stress-induced injury. These biological effects derive at least partially from the ability of this nitroxide to scavenge ROS/RNS, as shown in several studies in which it has been proposed that Tempol can alleviate inflammatory diseases and reduce formation of extracellular traps (ETs) through its action on these oxidants.<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">22,23,25</span></a> However, the beneficial anti-dyslipidemic effects of Tempol and its impact on cardiovascular events remain uncertain, and it is important to understand these actions by exploring different experimental animal models to find new therapeutic options. Therefore, the aim of this study was to assess the effects of Tempol on dyslipidemia and LVH in the well-established animal model of LDLr-/- mice.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Ethics statement</span><p id="par0030" class="elsevierStylePara elsevierViewall">All animal experiments were carried out in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals (National Institutes of Health, Washington DC: The National Academy Press, 2011). This study was approved by the ethics committee on the use of animals (CEUA) of the University José do Rosário Vellano (UNIFENAS), approval number 01 A/2015.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Animals and experimental design</span><p id="par0035" class="elsevierStylePara elsevierViewall">In this study, 40 three-month-old male mice, homozygous for the absence of the LDL receptor gene (LDLr-/-), background C57BL6, acquired from the Jackson Laboratory, Bar Harbor, Maine, USA and weighing approximately 22 g were used. These animals were supplied by the UNIFENAS breeding colony and were housed at a controlled temperature (25±1<span class="elsevierStyleHsp" style=""></span>°C) in a light-controlled room with a 12-h light/dark cycle. After acclimation, the mice were randomly and equally divided into five experimental groups of eight animals per group (n=8), constituted as follows.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Control groups</span><p id="par0040" class="elsevierStylePara elsevierViewall">The standard chow (SC) group were fed a standard chow (Nuvital<span class="elsevierStyleSup">®</span>, Nuvilab, Colombo, Brazil) for 30 days, and the high-fat diet (HFD) group were fed a high-fat diet (20% total fat, 1.25% cholesterol and 0.5% cholic acid; total 2.89 kcal/g; Instituto Tecnológico de Alimento, Campinas, SP, Brazil) for 30 days.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Treatment groups</span><p id="par0045" class="elsevierStylePara elsevierViewall">The standard chow + Tempol (SC+T) group were fed a standard diet (Nuvital<span class="elsevierStyleSup">®</span>) and treated with Tempol (97.0%, Sigma-Aldrich, St. Louis, MO, USA) for 30 days at a dose of 30 mg/kg administered by gavage once daily, and the high-fat diet + Tempol (HFD+T) group were fed a high-fat diet (20% total fat, 1.25% cholesterol, and 0.5% cholic acid) and treated with Tempol for 30 days at a dose of 30 mg/kg administered by gavage once daily. Additionally, another group (HFD+S) were fed a high-fat diet (20% total fat, 1.25% cholesterol, and 0.5% cholic acid) and treated with simvastatin (Medley, SP, Brazil) at a dose of 20 mg/kg administered by gavage once daily. All animals were fed their respective diets and received water ad libitum.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Biological samples</span><p id="par0050" class="elsevierStylePara elsevierViewall">After 30 days, mice were maintained on a fasting diet for 12 hours and then anesthetized by intramuscular injection of ketamine (40 mg/kg, Bayer AG and Parke-Davis<span class="elsevierStyleSup">®</span>, Berlin – Bayer, Leverkusen, Germany) and xylazine (6 mg/kg, Bayer AG and Parke-Davis<span class="elsevierStyleSup">®</span>, Berlin – Bayer, Leverkusen, Germany). Absence of the neuromuscular reflex was used to verify the anesthetic effect. Blood was collected via retro-orbital puncture (800 μl) using heparinized capillary tubes. After euthanasia and thoracotomy, 6 ml of 1.34 mM KCl was injected into the hearts through the left ventricle, and the organ was removed.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">26</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Analysis of lipid profiles</span><p id="par0055" class="elsevierStylePara elsevierViewall">Biochemical markers were assessed by standard methods using commercially available kits (Labtest, MG, Brazil). Plasma levels of total cholesterol (TC, Liquiform kit) and fractions (triglycerides [TG, GPO-ANA kit], high-density lipoprotein [HDL, cholesterol HDL kit], and low-density lipoprotein [LDL, cholesterol LDL kit]) were determined by the endpoint colorimetric method (absorbance values readable spectrophotometrically at 500 or 540 nm). The level of very low-density lipoprotein (VLDL) was determined as previously described.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Histological analysis of the heart</span><p id="par0060" class="elsevierStylePara elsevierViewall">Briefly, as previously described,<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">26</span></a> the mouse hearts were dissected and the left ventricles were fixed in 10% neutral-buffered formalin for 48 h, and the fixed specimens were processed by a conventional paraffin-embedding technique for histological serial sections of 3-μm thickness. The serial sections were collected from the same plane, deposited on slides, and stained with hematoxylin and eosin for morphological analysis (Nikon optical microscope, TNB-04T-PL, magnification 40× or 100×). Measurement of left ventricular thickness followed standard criteria, using LGMC-image software, version 1.0. All histological analyses were performed by a single examiner using the double-blind method.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">The effect of the intervention in the treatment groups was assessed with respect to TG, TC, VLDL, LDL, and HDL. Analysis of variance (ANOVA) was used to determine significant differences between the control and treated groups. Based on the results of the ANOVA/F test, orthogonal contrasts (comparisons) between the variables were performed, as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Before analysis of the data by ANOVA, the Shapiro-Wilk test (α=5%) was performed. This showed that the data had a normal distribution under the null hypothesis of normality for all groups regarding the variables (p>0.05). For comparisons of body weight, lipid profile markers and LVH, the mean values ± standard error of the mean (SEM) or standard deviation (SD) of at least three experiments are shown, and the variables were analyzed by ANOVA, followed by Tukey's, Scott-Knott's, and Bonferroni's tests for multiple comparisons of the means (α=5%). Additionally, interactions between the groups and times (0 and 30 days) were considered, with body weight being assessed at 0 and 30 days. The main effects were also assessed separately for groups and times in terms of body weight. Sisvar (Lavras, MG, Brazil, 2008) and BioEstat 5.0 (Belém, Pará, Brazil, 2007) were used for the statistical analysis.</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Effects of Tempol on the body weights of LDLr-/- mice</span><p id="par0075" class="elsevierStylePara elsevierViewall">Results of the comparisons of body weights according to the times at the beginning and end of the study period are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. No significant differences were observed between the groups over time (at 0 and after 30 days) (p>0.05) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, a). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> also shows the overall mean weight (all groups) at 0 and 30 days, which was observed to increase after 30 days of the experiment (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, b). In contrast, <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows that, in general, there was a decrease in mean body weight in the treated groups (SC+T, HFD+T, and HFD+S) compared to the control groups (SC and HFD vs. others) (p=0.000); however, there was no significant difference among the controls (SC vs. HFD). The treated groups did not differ statistically (p=0.886).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Effects of Tempol on triglycerides, total cholesterol, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein in LDLr-/- mice</span><p id="par0080" class="elsevierStylePara elsevierViewall">Treatment with Tempol in the HFD+T group had no effect on TC levels (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>), but prevented increases in plasma levels of TG, VLDL, and LDL compared with the control HFD group (<a class="elsevierStyleCrossRefs" href="#fig0015">Figures 3–5</a>). Regarding the orthogonal contrasts assessing the intervention for the treated groups vs. control groups (all untreated groups or baseline groups), <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows that the treated groups (SC+T, HFD+T, and HFD+S) differed from the untreated groups (SC and HFD) (p=0.000) in terms of TC; however, this variable did not differ significantly when the groups were compared to each other (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> also shows that TG levels fell in the treated groups compared with the untreated groups (p=0.000), a similar result to that presented in <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>. Regarding LDL (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>), the groups differed (p=0.000); the treated groups (SC+T, HFD+T, and HFD+S) presented lower mean LDL values than in the control groups (SC and HFD) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>). No significant difference (p=0.332) was observed between the HFD+T and HFD+S groups (<a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>). <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows that the treated groups (SC+T, HFD+T, and HFD+S) presented a decrease in VLDL compared to the control groups (SC and HFD) (p=0.000). There was no significant difference between the HFD+T and HFD+S groups (p=0.083) (<a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>). No significant differences were observed in HDL between the treated and untreated groups (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, p=0.1840) and among all groups (<a class="elsevierStyleCrossRef" href="#fig0030">Figure 6</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Effects of Tempol on cardiac damage and left ventricular hypertrophy in LDLr-/- mice</span><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding cardiac remodeling, representative histological images of the experimental groups are shown in <a class="elsevierStyleCrossRef" href="#fig0030">Figure 6</a>. The data show a correlation between morphology and left ventricular thickness. The mean thicknesses (in μm) in the five experimental groups are shown in <a class="elsevierStyleCrossRef" href="#fig0035">Figure 7</a>. There was no difference between the SC+T and SC groups (p=NS). Mean thickness was 0.6 μm less in the HFD+T group (p<0.05) than in the HFD group, and was 1.1 μm less in the HFD+S group (p<0.05) than in the HFD group and 0.5 μm less than in the HFD+T group. The difference between HFD+S and HFD+T was not significant (p>0.05) (<a class="elsevierStyleCrossRef" href="#fig0040">Figure 8</a>). <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows that, in general, the treated groups (SC+T, HFD+T, and HFD+S) presented less LVH than the control groups (SC and HFD) (p=0.003). Additionally, based on analyses between the individual groups (<a class="elsevierStyleCrossRef" href="#fig0035">Figure 7</a>), the control groups (baseline, SC and HFD) were significantly different from each other (p=0.001).</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia><elsevierMultimedia ident="fig0040"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">In this study, we used a well-established animal model of LDL receptor knockout (LDLr-/-) mice, whose genetic background combined with a high-fat diet (environmental factor) is likely to lead to the development of severe dyslipidemia, and hence a high risk of cardiovascular disease. During the study, LDLr-/- mice were fed a standard or a high-fat diet for 30 days. Administration of Tempol (30 mg/kg once daily for 30 days) in mice on a high-fat diet showed a strong protective effect in controlling dyslipidemia and preventing damage to heart tissue (mitigating LVH).</p><p id="par0095" class="elsevierStylePara elsevierViewall">LDLr-/- mice on a high-fat diet treated with Tempol showed a marked decrease in TG, LDL, and VLDL levels. Among the lipoproteins, LDL has been identified as one of the most important constituents of atheroma. As expected, LDLr-/- mice fed a high-fat diet presented a marked increase in LDL levels, and Tempol treatment decreased levels of this lipoprotein. Furthermore, increased TG levels have recently been shown to be associated with low HDL cholesterol levels, and hypertriglyceridemia is also one of the ‘deadly quartet,’ along with abdominal obesity, hypertension, and glucose intolerance.<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">7,28,29</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In our study, and in agreement with Kim et al.,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> LDLr-/- mice developed dyslipidemia with increases in TG, VLDL, and LDL (on a high-fat diet), and Tempol attenuated this condition; these results are similar to those found by Kim et al., in which Tempol treatment also prevented increases in these biomarkers of dyslipidemia.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Lipid disorders are among the most important risk factors for atherosclerotic cardiovascular disease, together with other chronic degenerative diseases with a prolonged natural history such as hypertension, obesity, and diabetes.<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">4–7</span></a> These diseases have a complex relationship with one another; lifestyle and genetic inheritance, among other factors, are common to their etiologies. Treatment of dyslipidemia has the fundamental purpose of primary and secondary prevention of coronary artery disease, cerebrovascular disease, and peripheral arterial disease, and may also lead to the regression of xanthomas and reduce the risk of acute pancreatitis.<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">30–32</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Unlike LDL, HDL functions primarily in reverse cholesterol transport, reducing the formation of atherosclerotic plaque.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">33</span></a> In this study, HDL and TC levels in LDLr-/- mice did not differ significantly among the five groups evaluated. By contrast, the plasma HDL levels found by Kim et al.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> demonstrated that treatment with Tempol of apoE-/- mice maintained on a high-fat diet promoted increases in HDL levels, but these differences may be due to the characteristics of the different animal models used.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">34</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Even on a normal diet, LDLr-/- mice may slowly develop dyslipidemia and atherosclerosis over time, and this process is accelerated with a high-fat diet.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">34</span></a> LDLr-/- mice develop moderate hypercholesterolemia (TC ∼250 mg/dl) when fed a standard diet and severe hypercholesterolemia when fed a high-fat diet. However, no differences between the groups were found regarding TC and HDL in this study; moreover, a closer relationship between these biomarkers was found. Furthermore, LDLr-/- mice normally become obese only when fed a high-fat diet with a fat content of more than 20%; thus, body weights differed only slightly among the groups, without statistical significance (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) since only up to 20% total fat was used in this study.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">34</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Simvastatin was used in this study as a control since this cholesterol-lowering agent is widely used preventively or as an adjuvant to correct lipid metabolism in patients with a predisposition to cardiovascular disease or primary hypercholesterolemia. Simvastatin is a prodrug that acts on the enzyme HMG-CoA reductase, preventing cholesterol synthesis and decreasing LDL, VLDL and TG.<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">19,35</span></a> This statin, at a dose of 20 mg/kg, had significant effects on lipid profile markers and LVH, and its effects on TG, LDL, VLDL, and LVH were statistically similar to those caused by 30 mg/kg Tempol.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In LVH, increases in myocyte volume, coronary artery wall thickness, capillary rarefaction and extracellular fibrosis, and changes in energy metabolism, intracellular calcium, and myocardial contractility and relaxation are normally observed.<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">13,14</span></a> LDLr-/- mice fed a high-fat diet for approximately 14 days develop atherosclerosis and an increased predisposition to cardiac damage, including LVH, with a mean 30% increase in cardiomyocyte diameter.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">26</span></a> In our study, morphological changes were observed in the untreated group of LDLr-/- mice fed a high-fat diet compared with those fed a standard diet, while treatment of these mice with Tempol attenuated these alterations, preventing LVH.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Regarding the underlying mechanisms, studies have shown that superoxide (O<span class="elsevierStyleInf">2</span><span class="elsevierStyleGlyphrad"></span>-) production in LDLr-/- mice fed a high-fat diet is significantly higher than in LDLr-/- mice fed standard chow.<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">36,37</span></a> Moreover, oxidative stress in these mice decreases nitric oxide (<span class="elsevierStyleGlyphrad"></span>NO) and increases LDL oxidation. Thus, it is possible that antioxidant treatment reduces cardiac oxidative stress and prevents LVH by mitigating pathogenic mechanisms such as oxidative stress-mediated fibrosis.<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">38</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Ulasova et al. showed that quercetin, an antioxidant, can prevent LVH in ApoE-/- hypercholesterolemic mice,<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">39</span></a> and other studies have shown that Tempol treatment can inhibit hypertension-induced oxidative stress-related LVH. In addition, Tempol (3 mmol) added to the drinking water of an experimental model of Dahl salt-sensitive rats for 10 weeks normalized LVH and reduced the cardiac expression of p22phox and Nox-2, mitochondrial uncoupling protein 2 and related oxidative stress. Thus, inhibition of cardiac ROS by Tempol prevented the cardiac fibrosis, remodeling and defective relaxation that underlie diastolic heart failure.<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">40–42</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The accumulated evidence suggests that Tempol can exert positive effects on dyslipidemia and prevent cardiac damage through multiple mechanisms; furthermore, a pleiotropic action is more plausible than a single mechanism in explaining the restoration of <span class="elsevierStyleGlyphrad"></span>NO and nitric oxide synthetase (NOS) (<span class="elsevierStyleGlyphrad"></span>NO is an important regulator of cardiac remodeling and is recognized as an anti-hypertrophic mediator).<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">43,44</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Furthermore, in this context, the action of Tempol in decreasing ROS is also relevant, since an increase in ROS in cardiomyocytes can activate the MAPK pathway, which has an important role in cardiac hypertrophy, and redox imbalance can also decrease the bioavailability of <span class="elsevierStyleGlyphrad"></span>NO.<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">43</span></a> Other ROS/RNS scavengers have been described as possible options for controlling atherosclerotic events and/or cardiovascular disease-related oxidative stress, since decreased antioxidant (i.e. SOD) activity and increased ROS generation have been described in such conditions, as in LVH.<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">45–50</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Several studies using other experimental models have reported the effects of Tempol on dyslipidemia, atherosclerotic events, and the cardiovascular system. The cardioprotective effect of Tempol demonstrated in this study using an LDLr-/- mice model is consistent with the findings of Zhu et al.,<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">51</span></a> who demonstrated the action of Tempol (500 μM) on O<span class="elsevierStyleInf">2</span><span class="elsevierStyleGlyphrad"></span>- in rat aortas, with a protective effect on the cardiovascular system by increasing the release of NO in the endothelium and causing vascular relaxation in aortas. Furthermore, the authors demonstrated that chronic treatment with Tempol (1 mM) added to the mice's drinking water restored the release of NO and aortic relaxation in rats.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Similarly to our findings, in an experimental model of rats with caerulein-induced pancreatitis, Marciniak et al.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">32</span></a> demonstrated that Tempol significantly decreased myocardial damage, mainly by attenuating oxidative stress-induced damage. Furthermore, as cited above, Kim et al.,<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">11</span></a> using an experimental ApoE-/- mouse model, showed that Tempol (10 mg/g added to feed) can improve lipid profile, reduce the formation of pro-inflammatory cytokines and markers such as monocyte chemotactic protein and myeloperoxidase, helping reduce atherosclerotic plaque area and risk of myocardial damage.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Our study has potential limitations. Assessment of oxidative damage by measuring oxidative stress indices would have helped to demonstrate the role of oxidants in the events described herein. Measurement of other biochemical parameters such as blood glucose, interleukin-6, monocyte-chemotactic protein, myeloperoxidase, and serum amyloid A could also have supplemented these findings and established a stronger link between dyslipidemia, the genesis of atherosclerotic events, and subsequent cardiovascular complications.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding the Tempol dose used in this study (30 mg/kg/day), other studies have reported the use of this nitroxide in animal models at doses of approximately 30 mg/kg or concentrations from 100 to 1000 μM/kg, once daily.<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">11,32,51</span></a> These doses and concentrations do not display in-vivo toxicity (even doses of 300 mg/kg/day or 87 μM/kg have no toxic effects in vivo),<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">23,52</span></a> are compatible with an EC50 for inhibiting the oxidative burst in vitro (50-400 μM),<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">53</span></a> and concentrations up to 1000 μM appear to be safe, i.e., it does not show in-vitro pro-oxidant effects,<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">54,55</span></a> which we consider may be a significant dose-limiting side effect in the systemic use of this nitroxide.</p><p id="par0170" class="elsevierStylePara elsevierViewall">In addition to Tempol's previously mentioned possible side effects, caution should be exercised with nitroxides and other antioxidants because of the reductive stress that can occur with excessive use of this and other antioxidants, which may have short-, medium- and long-term effects. It has been reported that antioxidants influence the immune response (acting mainly by inhibiting the oxidative burst) and the onset of chronic diseases, such as cancer and cardiovascular disease, including cardiomyopathy.<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">56</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">In summary, our study shows that the nitroxide Tempol is able to improve lipid profile and attenuate LVH in LDLr-/- mice fed a high-fat diet. These data suggest that this antioxidant can be a potent ally in preventing events related to cardiovascular disease.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Ethical disclosures</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Protection of human and animal subjects</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Confidentiality of data</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Right to privacy and informed consent</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflicts of interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres901271" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec882316" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres901270" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução e objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec882317" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Ethics statement" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Animals and experimental design" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Control groups" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Treatment groups" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Biological samples" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Analysis of lipid profiles" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Histological analysis of the heart" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0055" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Effects of Tempol on the body weights of LDLr-/- mice" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Effects of Tempol on triglycerides, total cholesterol, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein in LDLr-/- mice" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Effects of Tempol on cardiac damage and left ventricular hypertrophy in LDLr-/- mice" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:3 [ "identificador" => "sec0080" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack299789" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-06-16" "fechaAceptado" => "2017-02-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec882316" "palabras" => array:6 [ 0 => "Nitroxides" 1 => "Tempol" 2 => "Dyslipidemia" 3 => "Left ventricular hypertrophy" 4 => "Reactive oxygen species" 5 => "Reactive nitrogen species" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec882317" "palabras" => array:5 [ 0 => "Nitróxidos" 1 => "Tempol" 2 => "Dislipidemia" 3 => "Hipertrofia ventricular esquerda" 4 => "EROs/ERNs" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg). After 30 days of the diet/treatment, whole blood was collected for analysis of biochemical parameters (total cholesterol, triglycerides [TG], high-density lipoprotein [HDL], LDL, and very low-density lipoprotein [VLDL]). The heart was removed through thoracotomy and histological analysis of the left ventricle was performed.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A significant increase in TG, LDL, and VLDL and marked left ventricular hypertrophy (LVH) were demonstrated in the HFD group relative to the SC group (p<0.05), while Tempol treatment (HFD+T group) significantly (p<0.05) prevented increases in the levels of these lipid profile markers and attenuated LVH compared with the HFD group.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In this study, Tempol showed potential for the prevention of events related to serious diseases of the cardiovascular system.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdução e objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A dislipidemia está associada com aumento do risco para as doenças cardiovasculares e aterosclerose, refletindo na alta morbidade e mortalidade associadas. Este estudo investigou os efeitos do nitróxido <span class="elsevierStyleItalic">4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl</span> (tempol) sobre o perfil lipídico e a morfologia cardíaca em camundongos nocaute para o gene do receptor da lipoproteína de baixa densidade (LDLR KO ou LDL-/-).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Camundongos machos (três meses de idade, pesando aproximadamente 22 g) foram divididos nos seguintes grupos: grupos controlo: (1) ração padrão ([RP] n=8) = camundongos LDL-/- + dieta padrão; (2) dieta rica em lipídios ([DRL] n=8) = camundongos LDL-/- + DRL; e grupos tratados: (3) RP + tempol (RP + T, n=8) = camundongos LDL-/- + dieta padrão + tempol (30 mg/kg, administrado por gavagem, uma vez por dia); (4) DRL + tempol (DRL + T, n=8) = camundongos LDL-/- + DRL + tempol (30 mg/kg). Após 30 dias de dieta/tratamento, o sangue total foi obtido para análise dos parâmetros bioquímicos (colesterol total [CT], triglicerídeos [TG], HDL, LDL e VLDL) e, através de uma toracotomia, o coração foi removido e uma análise histológica do ventrículo esquerdo foi realizada.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Foi demonstrado um aumento significativo dos níveis de TG, LDL e VLDL, bem como uma considerável hipertrofia ventricular esquerda (HVE), no grupo DRL em comparação com o grupo RP (p<0,05); o tratamento com tempol (grupo DRL + T) preveniu significativamente (p<0,05) o aumento nos níveis destes marcadores de perfil lipídico e atenuou a HVE, em comparação com o grupo DRL.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusão</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Tempol apresentou potencial para a prevenção de eventos que podem levar a graves doenças do sistema cardiovascular.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introdução e objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusão" ] ] ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 517 "Ancho" => 2500 "Tamanyo" => 109754 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Orthogonal contrasts performed. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; SC: standard chow; SC+T: standard chow + Tempol.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1320 "Ancho" => 1565 "Tamanyo" => 58311 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Blood levels of total cholesterol in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; SC: standard chow; SC+T: standard chow + Tempol; TC: total cholesterol. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1322 "Ancho" => 1568 "Tamanyo" => 61539 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Blood levels of triglycerides in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; SC: standard chow; SC+T: standard chow + Tempol; TG: triglycerides. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1419 "Ancho" => 1573 "Tamanyo" => 66169 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Blood levels of low-density lipoprotein in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; LDL: low-density lipoprotein; SC: standard chow; SC+T: standard chow + Tempol. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1330 "Ancho" => 1565 "Tamanyo" => 59352 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Blood levels of very low-density lipoprotein in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; SC: standard chow; SC+T: standard chow + Tempol; VLDL: very low-density lipoprotein. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 1327 "Ancho" => 1571 "Tamanyo" => 55665 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Blood levels of high-density lipoprotein in the experimental groups fed a standard diet and a high-fat diet. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; HDL: high-density lipoprotein; SC: standard chow; SC+T: standard chow + Tempol. Values are mean ± standard error of the mean; α=0.05; *p<0.05.</p>" ] ] 6 => array:7 [ "identificador" => "fig0035" "etiqueta" => "Figure 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 1262 "Ancho" => 3162 "Tamanyo" => 551718 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Morphological analysis of the left ventricle in LDLr-/- mice fed a standard diet (above) and a high-fat diet (below). HFD: high-fat diet; HFD+T: high-fat diet + Tempol; SC: standard chow; SC+T: standard chow + Tempol; HFD+S: high-fat diet + simvastatin.</p>" ] ] 7 => array:7 [ "identificador" => "fig0040" "etiqueta" => "Figure 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 1356 "Ancho" => 1569 "Tamanyo" => 63357 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Mean left ventricular thickness in the study groups. HFD: high-fat diet; HFD+T: high-fat diet + Tempol; SC: standard chow; SC+T: standard chow + Tempol; HFD+S: high-fat diet + simvastatin. Values are mean ± standard deviation; α=0.05; *p<0.05.</p>" ] ] 8 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin; SC: standard chow; SC+T: standard chow + Tempol.</p>" "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">a. \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Times<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a></th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Experimental groups<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">0 days \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">30 days \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Weight (g)</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.47 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22.86 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.77 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.43 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC+T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.19 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.07 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.68 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.59 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.10 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.16 <span class="elsevierStyleSup">a</span><span class="elsevierStyleSup">A</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514185.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">b. Times (days) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Means<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.44 a \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21.84 b \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514187.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Means followed by the same superscript uppercase letter (row) do not differ by Tukey's test (α=5%).</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Means followed by the same superscript lowercase letter (column) do not differ by Tukey's test (α=5%).</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Means followed by the same letter do not differ statistically by the Student's t test (α=5%).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Means of body weights assessed in the study groups compared at 0 and 30 days.</p>" ] ] 9 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">HDL: high-density lipoprotein; HFD: high-fat diet; HFD+T: high-fat diet + Tempol; HFD+S: high-fat diet + simvastatin LDL: low-density lipoprotein; LVH: left ventricular hypertrophy; SC: standard chow; SC+T: standard chow + Tempol.</p>" "tablatextoimagen" => array:5 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HFD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">SC+T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HFD+T \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">HFD+S \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts (coefficients)</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514183.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Body weight</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total cholesterol</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">131.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-0.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.077<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">157.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.886<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.058<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.992<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-25.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.297<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514181.png" ] ] 2 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Triglycerides</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">LDL</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">164.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.007<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">162.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.016<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">216.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">144.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.014<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">117.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-25.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.696<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-36.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.332<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514186.png" ] ] 3 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">VLDL</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">HDL</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.077 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.990<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-22.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.221<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.000<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.535<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-18.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.083<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">-25.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.957<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514184.png" ] ] 4 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">LVH \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Contrasts</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimates \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC and HFD vs. others \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.456 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC vs. HFD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.812 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SC+T vs. HFD+T and HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.783 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.782<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HFD+T vs. HFD+S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.461 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.036<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1514182.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Significant at a nominal level of 5% (p<0.05).</p>" ] 1 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Significant at a nominal level of 1% (p<0.01).</p>" ] 2 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Not significant at a nominal level of 5% (p>0.05).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">p-values, estimates, and coefficients for the variables analyzed according to the orthogonal contrasts shown in <a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:56 [ 0 => array:3 [ "identificador" => "bib0285" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The epidemiology of cardiovascular disease in the UK 2014" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P. Bhatnagar" 1 => "K. Wickramasinghe" 2 => "J. Williams" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/heartjnl-2015-307516" "Revista" => array:6 [ "tituloSerie" => "Heart" "fecha" => "2015" "volumen" => "101" "paginaInicial" => "1182" "paginaFinal" => "1189" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26041770" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0290" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antioxidant-based therapies for angiotensin II-associated cardiovascular diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E.G. Rosenbaugh" 1 => "K.K. Savalia" 2 => "D.S. Manickam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpregu.00395.2012" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Regul Integr Comp Physiol" "fecha" => "2013" "volumen" => "304" "paginaInicial" => "R917" "paginaFinal" => "R928" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23552499" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0295" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization. The top 10 causes of death: major causes of death. Available at: <a href="http://www.who.int/mediacentre/factsheets/fs310/en/index2.html">http://www.who.int/mediacentre/factsheets/fs310/en/index2.html</a> [accessed November 2016]." ] ] ] 3 => array:3 [ "identificador" => "bib0300" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of coronary heart disease: the Framingham Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W.P. Castelli" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1984" "volumen" => "27" "paginaInicial" => "4" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13661183" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0305" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Obesity, hypertension, carbohydrate disorders and risk of chronic diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Z.P. Zimmet" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Med J Aust" "fecha" => "1986" "volumen" => "145" "paginaInicial" => "256" "paginaFinal" => "262" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3747912" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0310" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiovascular risks: new insights from Framingham" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D. Levy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am Heart J" "fecha" => "1988" "volumen" => "116" "paginaInicial" => "266" "paginaFinal" => "272" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3394638" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0315" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The deadly quartet" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N.M. Kaplan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "1989" "volumen" => "149" "paginaInicial" => "1514" "paginaFinal" => "1520" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2662932" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0320" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "American Heart Association call to action: obesity as a major risk factor for coronary heart disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R. Eckel" 1 => "R. Krauss" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" "fecha" => "1998" "volumen" => "97" "paginaInicial" => "2099" "paginaFinal" => "2100" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9626167" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0325" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Radicais livres na síndrome da isquemia e reperfusão" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W.B. Yoshida" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Cir Vasc Angiol" "fecha" => "1996" "volumen" => "12" "paginaInicial" => "82" "paginaFinal" => "95" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0330" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized factorial trial of vitamins C and E and beta-carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N.R. Cook" 1 => "C.M. Albert" 2 => "J.M. Gaziano" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2007" "volumen" => "67" "paginaInicial" => "1610" "paginaFinal" => "1618" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0335" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE-/- mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "C.H. Kim" 1 => "J.B. Mitchell" 2 => "C.A. Bursill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.atherosclerosis.2015.03.012" "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "2015" "volumen" => "240" "paginaInicial" => "234" "paginaFinal" => "241" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25818249" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0340" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial dynamics in cardiovascular health and disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.-B. Ong" 1 => "A.R. Hall" 2 => "D.J. Hausenloy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/ars.2012.4777" "Revista" => array:6 [ "tituloSerie" => "Antioxid Redox Signal" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "400" "paginaFinal" => "414" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22793879" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0345" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "From left ventricular hypertrophy to congestive heart failure: management of hypertensive heart disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.H. Gradman" 1 => "F. Alfayoumi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pcad.2006.02.001" "Revista" => array:6 [ "tituloSerie" => "Prog Cardiovasc Dis" "fecha" => "2006" "volumen" => "48" "paginaInicial" => "326" "paginaFinal" => "341" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16627048" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0350" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Echocardiographic left ventricular hypertrophy in hypertension: marker for future events or mediator of events?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P. Verdecchia" 1 => "F. Angeli" 2 => "P. Achilli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HCO.0b013e3280ebb413" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Cardiol" "fecha" => "2007" "volumen" => "22" "paginaInicial" => "329" "paginaFinal" => "334" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17556886" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0355" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.D. Lambeth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.freeradbiomed.2007.03.027" "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2007" "volumen" => "43" "paginaInicial" => "332" "paginaFinal" => "347" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17602948" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0360" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reciprocal relationship between reactive oxygen species and cyclooxygenase-2 and vascular dysfunction in hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Martínez-Revelles" 1 => "M.S. Avendaño" 2 => "A.B. García-Redondo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Antioxid Redox Signal" "fecha" => "2012" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0365" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lipoproteins nutrition, and heart disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E.J. Schaefer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Clin Nutr" "fecha" => "2002" "volumen" => "75" "paginaInicial" => "191" "paginaFinal" => "212" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11815309" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0370" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Understanding the essentials of blood lipid metabolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.J. Kingsbury" 1 => "G. Bondy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Prog Cardiovasc Nurs" "fecha" => "2003" "volumen" => "18" "paginaInicial" => "13" "paginaFinal" => "18" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12624568" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0375" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B.A. Golomb" 1 => "M.A. Evans" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Cardiovasc Drugs" "fecha" => "2008" "volumen" => "8" "paginaInicial" => "373" "paginaFinal" => "418" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19159124" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0380" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The chemistry and biology of nitroxide compounds" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "B.P. Soule" 1 => "F. Hyodo" 2 => "K. Matsumoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.freeradbiomed.2007.02.030" "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2007" "volumen" => "42" "paginaInicial" => "1632" "paginaFinal" => "1650" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17462532" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0385" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kinetics and mechanism of the comproportionation reaction between oxoammonium cation and hydroxylamine derived from cyclic nitroxides" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Israeli" 1 => "M. Patt" 2 => "M. Oron" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.freeradbiomed.2004.09.037" "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2005" "volumen" => "38" "paginaInicial" => "317" "paginaFinal" => "324" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15629861" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0390" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chemistry and antihypertensive effects of Tempol and other nitroxides" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.S. Wilcox" 1 => "A. Pearlman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1124/pr.108.000240" "Revista" => array:6 [ "tituloSerie" => "Pharmacol Rev" "fecha" => "2008" "volumen" => "60" "paginaInicial" => "418" "paginaFinal" => "469" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19112152" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0395" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of Tempol and redox-cycling nitroxides in models of oxidative stress" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.S. Wilcox" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pharmthera.2010.01.003" "Revista" => array:6 [ "tituloSerie" => "Pharmacol Ther" "fecha" => "2010" "volumen" => "126" "paginaInicial" => "119" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20153367" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0400" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Site-activity relationship of nitroxide radical's antioxidative effect" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.M. Samuni" 1 => "Y. Barenholz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2003" "volumen" => "34" "paginaInicial" => "177" "paginaFinal" => "185" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12521599" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0405" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Stable redox-cycling nitroxide Tempol inhibits NET formation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Hosseinzadeh" 1 => "P.K. Messer" 2 => "C.F. Urban" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fimmu.2012.00391" "Revista" => array:5 [ "tituloSerie" => "Front Immunol" "fecha" => "2012" "volumen" => "3" "paginaInicial" => "391" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23269921" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0410" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efeito anti-inflamatório da lipoproteína de alta densidade no sistema cardiovascular de camundongos hiperlipidêmicos" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.A.D. Garcia" 1 => "C.C. Lima" 2 => "L.B. Messora" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0870-2551(11)70024-5" "Revista" => array:6 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2011" "volumen" => "30" "paginaInicial" => "763" "paginaFinal" => "769" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22118127" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0415" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Tian" 1 => "H. Pei" 2 => "J.M. Sanders" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2006.04.180" "Revista" => array:6 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2006" "volumen" => "345" "paginaInicial" => "1004" "paginaFinal" => "1009" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16712797" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0420" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum triglycerides, to or not to be a risk factor for ischaemic heart disease?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.A. Carlson" 1 => "L.E. Böttiger" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Atherosclerosis" "fecha" => "1981" "volumen" => "39" "paginaInicial" => "289" "paginaFinal" => "291" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0425" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of triglycerides in coronary artery disease: lessons from the Prospective Cardiovascular Münster Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Assman" 1 => "H. Schulfe" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Cardiol" "fecha" => "1992" "volumen" => "70" "paginaInicial" => "10H" "paginaFinal" => "13H" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1466311" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0430" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma lipid and lipoprotein concentrations in Chinese males with coronary artery disease, with and without hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S.M. Shieh" 1 => "M. Shen" 2 => "M.M. Fuh" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Atherosclerosis" "fecha" => "1987" "volumen" => "67" "paginaInicial" => "49" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3675705" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0435" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cholesterol and cardiovascular disease: how strong is the evidence?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.L. La Rosa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Cardiol" "fecha" => "1992" "volumen" => "15" "numero" => "Suppl. III" "paginaInicial" => "2" "paginaFinal" => "7" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0440" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Article ID 4139851, 7 pp." "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tempol, a membrane-permeable radical scavenger, exhibits anti-inflammatory and cardioprotective effects in the cerulein-induced pancreatitis rat model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Marciniak" 1 => "B. Walczyna" 2 => "G. Rajtar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Oxid Med Cell Longev" "fecha" => "2016" "volumen" => "2016" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0445" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Regression of atherosclerosis. Benefit can be expected from low LDL-C and high HDL-C levels" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.C. Arntzenius" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Cardiol" "fecha" => "1991" "volumen" => "4" "paginaInicial" => "431" "paginaFinal" => "438" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0450" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mouse models of the metabolic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.J. Kennedy" 1 => "K.L.J. Ellacott" 2 => "V.L. King" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1242/dmm.003467" "Revista" => array:6 [ "tituloSerie" => "Dis Model Mech" "fecha" => "2010" "volumen" => "3" "paginaInicial" => "156" "paginaFinal" => "166" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20212084" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0455" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microemulsion liquid chromatographic screening of simvastatin and its active metabolite in human plasma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Malenovic" 1 => "B. Jancic-stojanovic" 2 => "M. Medenica" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Chromatogr" "fecha" => "2008" "volumen" => "20" "paginaInicial" => "595" "paginaFinal" => "607" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0460" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antiatherogenic effects of S-nitroso-N-acetylcysteine in hypercholesterolemic LDL receptor knockout mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M.H. Krieger" 1 => "K.F.R. Santos" 2 => "S.M. Shishido" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.niox.2005.07.011" "Revista" => array:6 [ "tituloSerie" => "Nitric Oxide" "fecha" => "2006" "volumen" => "14" "paginaInicial" => "12" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16198610" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0465" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardioprotective mechanism of S-nitroso-N-acetylcysteine via S-nitrosated betadrenoceptor-2 in the LDLr-/- mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.C. Wanschel" 1 => "V.M. Caceres" 2 => "A.I. Moretti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.niox.2013.12.003" "Revista" => array:6 [ "tituloSerie" => "Nitric Oxide" "fecha" => "2014" "volumen" => "36" "paginaInicial" => "58" "paginaFinal" => "66" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24333561" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0470" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tempol inhibits TGF-β and MMPs upregulation and prevents cardiac hypertensive changes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E. Rizzi" 1 => "M.M. Castro" 2 => "C.S. Ceron" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijcard.2011.08.060" "Revista" => array:6 [ "tituloSerie" => "Int J Cardiol" "fecha" => "2013" "volumen" => "165" "paginaInicial" => "165" "paginaFinal" => "173" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21917342" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0475" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quercetin prevents left ventricular hypertrophy in the Apo E knockout mouse" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E. Ulasova" 1 => "J. Perez" 2 => "B.J. Hill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.redox.2013.07.001" "Revista" => array:6 [ "tituloSerie" => "Redox Biol" "fecha" => "2013" "volumen" => "1" "paginaInicial" => "381" "paginaFinal" => "386" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24024175" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0480" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Contribution of reactive oxygen species to the pathogenesis of left ventricular failure in Dahl salt-sensitive hypertensive rats: effects of angiotensin II blockade" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "P. Guo" 1 => "A. Nishiyama" 2 => "M. Rahman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.hjh.0000226200.73065.5d" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "1097" "paginaFinal" => "1104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16685210" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0485" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Matsui" 1 => "K. Ando" 2 => "H. Kawarazaki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.108.111815" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2008" "volumen" => "52" "paginaInicial" => "287" "paginaFinal" => "294" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18606904" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0490" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paradoxical mineralocorticoid receptor activation and left ventricular diastolic dysfunction under high oxidative stress conditions" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "H. Wang" 1 => "T. Shimosawa" 2 => "H. Matsui" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/HJH.0b013e328300a232" "Revista" => array:6 [ "tituloSerie" => "J Hypertens" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "1453" "paginaFinal" => "1462" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18551023" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0495" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors and mechanisms involved in left ventricular hypertrophy and the anti-hypertrophic role of nitric oxide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.A.D. Garcia" 1 => "E.K. Incerpi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arq Bras Cardiol" "fecha" => "2008" "volumen" => "90" "paginaInicial" => "409" "paginaFinal" => "416" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18592095" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0500" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nitroxide pharmaceutical development for age-related degeneration and disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.A. Zarling" 1 => "V.E. Brunt" 2 => "A.K. Vallerga" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fgene.2015.00325" "Revista" => array:5 [ "tituloSerie" => "Front Genet" "fecha" => "2015" "volumen" => "6" "paginaInicial" => "325" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26594225" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0505" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased SOD activity and increased nitrates level in rat heart with left ventricular hypertrophy induced by isoproterenol" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "N. Balta" 1 => "I. Stojan" 2 => "C. Petec" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rom J Physiol" "fecha" => "1999" "volumen" => "36" "paginaInicial" => "175" "paginaFinal" => "182" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11797933" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0510" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extracellular superoxide dismutase deficiency exacerbates pressure overload-induced left ventricular hypertrophy and dysfunction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Z. Lu" 1 => "X. Xu" 2 => "X. Hu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.107.098186" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2008" "volumen" => "51" "paginaInicial" => "19" "paginaFinal" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17998475" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0515" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Article ID 293769, 13 pp." "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ROS and RNS signaling in heart disorders: could antioxidant treatment be successful?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "I. Afanas’ev" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Oxid Med Cell Longev" "fecha" => "2011" "volumen" => "2011" ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0520" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mito-tempol and dexrazoxane exhibit cardioprotective and chemotherapeutic effects through specific protein oxidation and autophagy in a syngeneic breast tumor preclinical model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.S. Dickey" 1 => "Y. Gonzalez" 2 => "B. Aryal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0070575" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "e70575" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23940596" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0525" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extracellular SOD protects the heart against oxidative stress and hypertrophy after myocardial infarction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "E.D. van Deel" 1 => "Z. Lu" 2 => "X. Xu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.freeradbiomed.2007.12.007" "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2008" "volumen" => "44" "paginaInicial" => "1305" "paginaFinal" => "1313" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18206658" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0530" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of nitric oxide and nitroxide SOD-mimic on the recovery of isolated rat heart following ischemia and reperfusion" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A. Hoffman" 1 => "S. Goldstein" 2 => "A. Samuni" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochem Pharmacol" "fecha" => "2003" "volumen" => "66" "paginaInicial" => "1279" "paginaFinal" => "1286" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14505807" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0535" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca<span class="elsevierStyleSup">2+</span> signaling and NO production in rat aorta" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Zhu" 1 => "N. Drenjancevic-Peric" 2 => "E. McEwen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpheart.00692.2005" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Heart Circ Physiol" "fecha" => "2006" "volumen" => "291" "paginaInicial" => "H929" "paginaFinal" => "H938" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16603691" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0540" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A phase I study of topical Tempol for the prevention of alopecia induced by whole brain radiotherapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J.M. Metz" 1 => "D. Smith" 2 => "R. Mick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-04-0658" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2004" "volumen" => "10" "paginaInicial" => "6411" "paginaFinal" => "6417" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15475427" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0545" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of cyclic AMP production by signal transduction pathways in preglomerular microvessels and microvascular smooth muscle cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.C. Jackson" 1 => "Z. Mi" 2 => "E.K. Jackson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1124/jpet.103.063081" "Revista" => array:6 [ "tituloSerie" => "J Pharmacol Exp Ther" "fecha" => "2004" "volumen" => "310" "paginaInicial" => "349" "paginaFinal" => "358" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15087474" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0550" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dual activity of nitroxides as pro- and antioxidants: catalysis of copper-mediated DNA breakage and H<span class="elsevierStyleInf">2</span>O<span class="elsevierStyleInf">2</span> dismutation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "Y. Aronovitch" 1 => "D. Godinger" 2 => "A. Israeli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.freeradbiomed.2007.01.017" "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2007" "volumen" => "42" "paginaInicial" => "1317" "paginaFinal" => "1325" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17395005" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0555" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pro-oxidative activity of nitroxides in their reactions with glutathione" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "J. Głebska" 1 => "J. Skolimowski" 2 => "Z. Kudzin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Free Radic Biol Med" "fecha" => "2003" "volumen" => "35" "paginaInicial" => "310" "paginaFinal" => "316" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12885593" "web" => "Medline" ] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0560" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.C. Brewer" 1 => "S.B. Mustafi" 2 => "T.V.A. Murray" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/ars.2012.4914" "Revista" => array:6 [ "tituloSerie" => "Antioxid Redox Signal" "fecha" => "2013" "volumen" => "18" "paginaInicial" => "1114" "paginaFinal" => "1127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22938199" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack299789" "titulo" => "Acknowledgments" "texto" => "<p id="par0200" class="elsevierStylePara elsevierViewall">This research was supported by a grant from <span class="elsevierStyleGrantSponsor" id="gs1">Fundação de Amparo à Pesquisa do Estado de Minas Gerais</span>.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000003600000009/v1_201709150927/S0870255117305450/v1_201709150927/en/main.assets" "Apartado" => array:4 [ "identificador" => "29261" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Artigos Originais" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000003600000009/v1_201709150927/S0870255117305450/v1_201709150927/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255117305450?idApp=UINPBA00004E" ]
| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 9 | 6 | 15 |
| 2024 Outubro | 49 | 32 | 81 |
| 2024 Setembro | 72 | 22 | 94 |
| 2024 Agosto | 53 | 38 | 91 |
| 2024 Julho | 42 | 32 | 74 |
| 2024 Junho | 49 | 25 | 74 |
| 2024 Maio | 46 | 24 | 70 |
| 2024 Abril | 47 | 31 | 78 |
| 2024 Maro | 40 | 23 | 63 |
| 2024 Fevereiro | 36 | 19 | 55 |
| 2024 Janeiro | 29 | 24 | 53 |
| 2023 Dezembro | 35 | 18 | 53 |
| 2023 Novembro | 89 | 27 | 116 |
| 2023 Outubro | 25 | 27 | 52 |
| 2023 Setembro | 27 | 18 | 45 |
| 2023 Agosto | 55 | 23 | 78 |
| 2023 Julho | 31 | 9 | 40 |
| 2023 Junho | 34 | 10 | 44 |
| 2023 Maio | 50 | 34 | 84 |
| 2023 Abril | 33 | 9 | 42 |
| 2023 Maro | 46 | 19 | 65 |
| 2023 Fevereiro | 43 | 19 | 62 |
| 2023 Janeiro | 36 | 13 | 49 |
| 2022 Dezembro | 55 | 26 | 81 |
| 2022 Novembro | 70 | 35 | 105 |
| 2022 Outubro | 41 | 17 | 58 |
| 2022 Setembro | 43 | 38 | 81 |
| 2022 Agosto | 42 | 36 | 78 |
| 2022 Julho | 54 | 38 | 92 |
| 2022 Junho | 32 | 27 | 59 |
| 2022 Maio | 67 | 39 | 106 |
| 2022 Abril | 65 | 34 | 99 |
| 2022 Maro | 29 | 50 | 79 |
| 2022 Fevereiro | 53 | 34 | 87 |
| 2022 Janeiro | 72 | 36 | 108 |
| 2021 Dezembro | 34 | 35 | 69 |
| 2021 Novembro | 48 | 38 | 86 |
| 2021 Outubro | 40 | 61 | 101 |
| 2021 Setembro | 41 | 31 | 72 |
| 2021 Agosto | 37 | 41 | 78 |
| 2021 Julho | 29 | 43 | 72 |
| 2021 Junho | 28 | 27 | 55 |
| 2021 Maio | 33 | 34 | 67 |
| 2021 Abril | 82 | 43 | 125 |
| 2021 Maro | 64 | 26 | 90 |
| 2021 Fevereiro | 70 | 20 | 90 |
| 2021 Janeiro | 52 | 24 | 76 |
| 2020 Dezembro | 40 | 11 | 51 |
| 2020 Novembro | 30 | 23 | 53 |
| 2020 Outubro | 33 | 14 | 47 |
| 2020 Setembro | 41 | 11 | 52 |
| 2020 Agosto | 28 | 9 | 37 |
| 2020 Julho | 49 | 10 | 59 |
| 2020 Junho | 41 | 16 | 57 |
| 2020 Maio | 58 | 8 | 66 |
| 2020 Abril | 58 | 13 | 71 |
| 2020 Maro | 40 | 13 | 53 |
| 2020 Fevereiro | 130 | 20 | 150 |
| 2020 Janeiro | 28 | 20 | 48 |
| 2019 Dezembro | 46 | 8 | 54 |
| 2019 Novembro | 53 | 13 | 66 |
| 2019 Outubro | 36 | 6 | 42 |
| 2019 Setembro | 31 | 7 | 38 |
| 2019 Agosto | 31 | 7 | 38 |
| 2019 Julho | 41 | 10 | 51 |
| 2019 Junho | 35 | 16 | 51 |
| 2019 Maio | 50 | 15 | 65 |
| 2019 Abril | 30 | 49 | 79 |
| 2019 Maro | 140 | 23 | 163 |
| 2019 Fevereiro | 171 | 15 | 186 |
| 2019 Janeiro | 84 | 6 | 90 |
| 2018 Dezembro | 123 | 12 | 135 |
| 2018 Novembro | 252 | 9 | 261 |
| 2018 Outubro | 676 | 36 | 712 |
| 2018 Setembro | 136 | 11 | 147 |
| 2018 Agosto | 38 | 14 | 52 |
| 2018 Julho | 28 | 7 | 35 |
| 2018 Junho | 50 | 9 | 59 |
| 2018 Maio | 48 | 6 | 54 |
| 2018 Abril | 57 | 20 | 77 |
| 2018 Maro | 64 | 9 | 73 |
| 2018 Fevereiro | 27 | 17 | 44 |
| 2018 Janeiro | 47 | 7 | 54 |
| 2017 Dezembro | 50 | 32 | 82 |
| 2017 Novembro | 61 | 20 | 81 |
| 2017 Outubro | 99 | 40 | 139 |
| 2017 Setembro | 47 | 41 | 88 |
| 2017 Agosto | 14 | 18 | 32 |
Mostrar tudo
