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Decreasing doxorubicin-induced cardiotoxicity with Nigella sativa seed extract: Traditional medicine targeting a severe clinical problem
Diminuição da cardiotoxicidade da doxorubicina com extratos de sementes de Nigella sativa: medicina tradicional direcionada a um problema clínico severo
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95% confidence interval 0.624 to 0.941) in preterm newborns with gestational age between 23 and 32 weeks.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Joana Santos, Paulo Soares, Cristina Ferreras, Filipa Flor-de-Lima, Hercília Guimarães" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Joana" "apellidos" => "Santos" ] 1 => array:2 [ "nombre" => "Paulo" "apellidos" => "Soares" ] 2 => array:2 [ "nombre" => "Cristina" "apellidos" => "Ferreras" ] 3 => array:2 [ "nombre" => "Filipa" "apellidos" => "Flor-de-Lima" ] 4 => array:2 [ "nombre" => "Hercília" "apellidos" => "Guimarães" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255121001670?idApp=UINPBA00004E" "url" => "/08702551/0000004100000002/v1_202202160601/S0870255121001670/v1_202202160601/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S087025512100442X" "issn" => "08702551" "doi" => "10.1016/j.repc.2020.12.015" "estado" => "S300" "fechaPublicacion" => "2022-02-01" "aid" => "1843" "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. 2022;41:99-105" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Prevention of doxorubicin-induced experimental cardiotoxicity by <span class="elsevierStyleItalic">Nigella sativa</span> in rats" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "99" "paginaFinal" => "105" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Prevenção da cardiotoxicidade da doxorrubicina pela <span class="elsevierStyleItalic">Nigella sativa</span> em ratos" ] ] "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" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1053 "Ancho" => 1500 "Tamanyo" => 399087 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Histopathologic images of study groups (hematoxylin and eosin, ×200). (A) Normal myocyte alignment in the control group (n=7); (B) severe myocyte disarray and hypertrophy in the DOX group (n=7); (C) normal myocyte alignment in the NS group (n=7); (D) significantly less myocyte disarray and hypertrophy in DOX+NS rats vs. DOX rats (n=7).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mehmet Şahin Adıyaman, Özlem Aba Adıyaman, Adile Ferda Dağlı, Mehmet Zülkif Karahan, Mustafa Necati Dağlı" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Mehmet Şahin" "apellidos" => "Adıyaman" ] 1 => array:2 [ "nombre" => "Özlem Aba" "apellidos" => "Adıyaman" ] 2 => array:2 [ "nombre" => "Adile Ferda" "apellidos" => "Dağlı" ] 3 => array:2 [ "nombre" => "Mehmet Zülkif" "apellidos" => "Karahan" ] 4 => array:2 [ "nombre" => "Mustafa Necati" "apellidos" => "Dağlı" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S087025512100442X?idApp=UINPBA00004E" "url" => "/08702551/0000004100000002/v1_202202160601/S087025512100442X/v1_202202160601/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial comment</span>" "titulo" => "Decreasing doxorubicin-induced cardiotoxicity with <span class="elsevierStyleItalic">Nigella sativa</span> seed extract: Traditional medicine targeting a severe clinical problem" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "107" "paginaFinal" => "108" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Paulo J. Oliveira" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Paulo J." "apellidos" => "Oliveira" "email" => array:1 [ 0 => "pauloliv@cnc.uc.pt" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "CNC - Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "UC-Biotech, University of Coimbra, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Diminuição da cardiotoxicidade da doxorubicina com extratos de sementes de Nigella sativa: medicina tradicional direcionada a um problema clínico severo" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Anthracyclines are a family of approved anticancer agents that are clinically effective for treating both solid tumors and leukemias. One member, doxorubicin (DOX), is one of the most frequently prescribed chemotherapeutic drugs worldwide, due to its broad spectrum of therapeutic efficacy. DOX is effective against various types of cancer, among them leukemias, lymphomas, and several solid tumors, including gynecological, urogenital, endocrine, breast and brain tumors, stomach cancer, and Ewing and Kaposi's sarcoma. As with other anticancer agents, the clinical use of DOX is associated with several off-target effects. Notably, the most limiting adverse DOX side-effect is the incidence of cardiovascular toxicity, resulting in hypotension, tachycardia, arrhythmias, and ultimately the development of congestive heart failure, the most serious and dose-limiting consequence, if not detected in time.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Acute DOX toxicity is rarely severe. It may involve transient electrophysiological alterations, which can occur immediately after each treatment or appear a week after the last course,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> disappearing with cessation of the treatment. Some reports indicate that pericarditis or myocarditis may play a part in some severe or even fatal events, resulting from cardiomyocyte damage and release of proinflammatory molecules<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> or from the activation of NF-κB.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Cardiomyopathy and eventual congestive heart failure are the most severe events associated with DOX therapy. The incidence of DOX cardiomyopathy in treated patients depends on the cumulative treatment dose used, rising to 36% when the dose exceeds 600 mg/m<span class="elsevierStyleSup">2</span>. Heart failure affects 26% of patients receiving DOX in a cumulative dose exceeding 550 mg/m<span class="elsevierStyleSup">2</span>.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Early-onset and progressive DOX cardiotoxicity may occur within a year or not become apparent until years after the last treatment course. It can manifest as chronic dilated cardiomyopathy in adult patients or as restrictive cardiomyopathy in pediatric patients, who have decreased left ventricular ejection fraction, and occasionally results in fatal events.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> Importantly, early detection of subclinical cardiovascular events caused by DOX within the first year post-treatment can result in total or partial recovery of cardiac function.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Many mechanisms underlie DOX cardiotoxicity, prominent among which is increased generation of reactive oxygen species. In the early 1980s, Davies and Doroshow proposed that DOX undergoes redox cycling in cardiac mitochondria, being activated to a highly reactive semi-quinone, which reacts with oxygen to produce the superoxide anion.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> The extensive network of mitochondria in the cardiomyocyte and lower efficacy of the antioxidant network in the heart compared to other tissues may explain the selective cardiotoxicity.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Mitochondrial alterations, including reduced capacity to produce adenosine triphosphate (ATP), combined with altered metabolic and transcriptomic profiles, are also involved in DOX cardiomyopathy.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Hundreds of publications have proposed different molecules capable of decreasing DOX cardiotoxicity. Potential interventions to reduce this cardiotoxicity have mostly revolved around the pro-oxidant nature that underlie the side effects. So far, dexrazoxane is the only FDA-approved protective therapy against DOX toxicity. Its mechanism of protection is not entirely clear. Although it was initially thought to be mediated by iron chelation, thus indirectly decreasing oxidative stress through Fenton-type reactions, potent iron chelators such as desferrioxamine B do not confer the same degree of cardioprotection.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> Inhibition of cardiac nuclear topoisomerase II beta and inhibition of DOX-induced DNA breaks are also possible mechanisms for cardioprotection by dexrazoxane.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Several natural molecules have been tested for prevention of DOX cardiotoxicity, including melatonin, genistein, vitamin E, caffeic acid phenethyl ester and epigallocatechin-3-gallate, to mention a few.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The paper by Adıyaman et al. published in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> reports the protection afforded against DOX cardiotoxicity by <span class="elsevierStyleItalic">Nigella sativa</span> (NS), a flowering plant in the Ranunculacea family, in the form of its black seeds. The plant has a widespread distribution, including southwest Asia, the Mediterranean, India and the Middle East.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The authors used an in vivo rat model of DOX cardiotoxicity, with a single 10 mg/kg intraperitoneal dose. The animals in the NS group were given standard rodent feed together with a daily 100 mg/kg dose of NS extract diluted in water and administered through gavage for 35 days. A single 10 mg/kg intraperitoneal dose of DOX was administered on day 28. The protocol used by the authors resulted in DOX-induced cardiotoxicity, as observed by a significant increase in troponin and NT-proBNP levels. Animals in the NS+DOX group showed lower markers of cardiac toxicity markers, including histological markers. A potential mechanism for the protection observed involves antioxidant protection, since animals in the NS+DOX group showed higher total serum antioxidant capacity and lower oxidative stress markers than animals treated only with DOX.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Although this study is very promising, there are two points requiring caution. The extracts used contain thymoquinone, which in large amounts can cause liver toxicity. High dosages of NS also have proinflammatory effects, which means that uncontrolled use of the extract to counteract DOX cardiotoxicity may be hazardous. Secondly, the effects of NS on the anticancer effects of DOX were not determined. Ideally, protective agents should have no effect or even increase the anticancer activity of the primary treatment.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Despite these potential caveats, the paper by Adıyaman et al. adds another natural extract to the list of coadjuvants that potentially reduce DOX cardiotoxicity. Follow-up studies aimed to address the above points and to identify the active components responsible for cardioprotection should increase the interest in this extract in the context of anthracycline cardiotoxicity.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.M. 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Dağlı" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Rev Port Cardiol" "fecha" => "2022" "volumen" => "41" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/08702551/0000004100000002/v1_202202160601/S0870255121004510/v1_202202160601/en/main.assets" "Apartado" => array:4 [ "identificador" => "92834" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/08702551/0000004100000002/v1_202202160601/S0870255121004510/v1_202202160601/en/main.pdf?idApp=UINPBA00004E&text.app=https://revportcardiol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255121004510?idApp=UINPBA00004E" ]
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| 2024 Maro | 30 | 21 | 51 |
| 2024 Fevereiro | 58 | 26 | 84 |
| 2024 Janeiro | 49 | 28 | 77 |
| 2023 Dezembro | 21 | 29 | 50 |
| 2023 Novembro | 30 | 20 | 50 |
| 2023 Outubro | 29 | 23 | 52 |
| 2023 Setembro | 21 | 23 | 44 |
| 2023 Agosto | 21 | 23 | 44 |
| 2023 Julho | 35 | 10 | 45 |
| 2023 Junho | 32 | 11 | 43 |
| 2023 Maio | 45 | 26 | 71 |
| 2023 Abril | 17 | 4 | 21 |
| 2023 Maro | 34 | 20 | 54 |
| 2023 Fevereiro | 27 | 23 | 50 |
| 2023 Janeiro | 22 | 21 | 43 |
| 2022 Dezembro | 36 | 26 | 62 |
| 2022 Novembro | 48 | 31 | 79 |
| 2022 Outubro | 29 | 35 | 64 |
| 2022 Setembro | 27 | 47 | 74 |
| 2022 Agosto | 37 | 40 | 77 |
| 2022 Julho | 32 | 38 | 70 |
| 2022 Junho | 36 | 47 | 83 |
| 2022 Maio | 23 | 35 | 58 |
| 2022 Abril | 24 | 34 | 58 |
| 2022 Maro | 42 | 61 | 103 |
| 2022 Fevereiro | 69 | 89 | 158 |
| 2022 Janeiro | 8 | 17 | 25 |
| 2021 Dezembro | 20 | 33 | 53 |
| 2021 Novembro | 20 | 19 | 39 |
Mostrar tudo
