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 As₂O₃ 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As₂O₃ significantly 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 As₂O₃ significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As₂O₃ treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψ_m). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψ_m. These findings suggested that the ω-3 fatty acid has the potential to protect against As₂O₃-induced cardiotoxicity.

Keywords: Arsenic deposition; Arsenic trioxide; Cardioprotection; Micronuclei; Omega-3 fatty acid.