Grape seed and skin extract protects against arsenic trioxide induced oxidative stress in rat heart

Abstract

Arsenic is a metalloid found in water, soil, and air from natural and anthropogenic sources, and is commonly found in inorganic as well as organic forms. The clinical use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) is limited by its cardiotoxic side effects. Grape seed and skin extract (GSSE) is a polyphenolic mixture with antioxidant properties. This study aimed to evaluate the protective effect of GSSE on arsenic-induced cardiac oxidative stress and injury. Animals exposed to 2.5 mg/kg As2O3 for 21 days exhibited a relevant increase in heart lipoperoxidation, protein carbonylation, and inflammation, as well as a drop in the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, As2O3 disturbed heart lipidemia and lipase activity, transition metals distribution and the associated enzymes, intracellular mediators such as calcium and the associated calpain activity, as well as myocardial architecture. Treatment with 4 g/kg GSSE protected against most of the deleterious effects provoked by As2O3. Our data suggest that GSSE has the potential to protect against As2O3-induced cardiotoxicity.