Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.

Arsenic trioxide (AsO) 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 AsO-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with AsO 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. AsO 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 AsO. ω-3 fatty acid co-administration with AsO significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, AsO treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψ). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψ. These findings suggested that the ω-3 fatty acid has the potential to protect against AsO-induced cardiotoxicity.