title: Cardioprotective effects of curcumin and nebivolol against doxorubicin-induced cardiac toxicity in rats.
abstract: Doxorubicin (DOX) is used in the treatment of cancer. However, cardiotoxicity is its major dose-limiting factor. Mechanism of DOX-cardiac toxicity is not completely elucidated. The aim of the current study was to explore whether the addition of subeffective dose of curcumin (100 mg/kg) to nebivolol would produce a better impact in treating DOX-induced cardiac toxicity in comparison with monotherapy. Male rats were used and subdivided into seven groups. Cardiac toxicity was induced in 6 groups by intraperitoneal injection of DOX over 23 days; of the six groups, five groups were treated with curcumin (100 and 200 mg/kg), nebivolol (1 and 2 mg/kg), and their combination; the sixth group was the control group used for comparison. Oral administration of curcumin and/or nebivolol attenuated DOX cardiotoxicity as manifested by increasing survival rate, improvement in body weight, heart index, and ECG parameters, increase in ventricular isoprenaline responses, and improvement in cardiac enzymes, oxidative stress, apoptosis, and histopathological picture. The addition of the current low subeffective dose of curcumin to nebivolol ameliorated DOX cardiac toxicity to a much greater extent than monotherapy showing better antioxidant and antiapoptotic effects versus the per se effect of nebivolol. Therefore, the current study encourages adding low dose of curcumin to potentiate the effect of nebivolol in the clinical management of cardiac toxicity improving the patients' quality of life if proper clinical safety data are available.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: S
authors.initials: S
authors.lastname: Imbaby
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Ewais
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt sohaessawy@yahoo.com.
authors.forename: S
authors.initials: S
authors.lastname: Essawy
authors.affiliation: Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
authors.forename: N
authors.initials: N
authors.lastname: Farag
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000068577:Nebivolol; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001578:Benzopyrans; D015415:Biomarkers; D002316:Cardiotonic Agents; D004272:DNA, Mitochondrial; D004983:Ethanolamines; D000068577:Nebivolol; D004317:Doxorubicin; D003474:Curcumin
keywords: Cardiac toxicity; DOX; curcumin; nebivolol; nitric oxide; oxidative stress