title: Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.
abstract: Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O34 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with As2O3. ω-3 fatty acid co-administration with As2O3significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψm). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψm. These findings suggested that the ω-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity.
authors.affiliation: School of Biosciences, Mahatma Gandhi University, P.D Hills P.O, Kottayam, Kerala, 686560, India.
authors.forename: Mathews V
authors.initials: MV
authors.lastname: Varghese
authors.affiliation: School of Biosciences, Mahatma Gandhi University, P.D Hills P.O, Kottayam, Kerala, 686560, India.
authors.forename: M
authors.initials: M
authors.lastname: Abhilash
authors.affiliation: School of Biosciences, Mahatma Gandhi University, P.D Hills P.O, Kottayam, Kerala, 686560, India.
authors.forename: M V Sauganth
authors.initials: MV
authors.lastname: Paul
authors.affiliation: School of Biosciences, Mahatma Gandhi University, P.D Hills P.O, Kottayam, Kerala, 686560, India.
authors.forename: Manju
authors.initials: M
authors.lastname: Alex
authors.affiliation: School of Biosciences, Mahatma Gandhi University, P.D Hills P.O, Kottayam, Kerala, 686560, India. harinair@mgu.ac.in.
authors.forename: R Harikumaran
authors.initials: RH
authors.lastname: Nair
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D066126:Cardiotoxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000633:toxicity*; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001152:Arsenicals; D015415:Biomarkers; D004338:Drug Combinations; C045153:Maxepa; D010087:Oxides; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D000077237:Arsenic Trioxide; D002118:Calcium
keywords: Arsenic deposition; Arsenic trioxide; Cardioprotection; Micronuclei; Omega-3 fatty acid