Evaluation of Antiperoxidative Potential of Ascorbic Acid on Busulfan-induced Lipid Peroxidation Using 4-hydroxy-2-nonenal and Nitric Oxide as Model Markers

The study was designed with an aim to evaluate the antiperoxidative potential of ascorbic acid on busulfan-induced lipid peroxidation. The study was performed in vitro using goat liver as lipid source. This evaluation was done by measuring the 4-hydroxy-2-nonenal (4-HNE) and nitric oxide (NO) content of liver tissue homogenates as markers of lipid peroxidation. The study reveals the lipid peroxidation induction capacity of busulfan and the antiperoxidative potential of ascorbic acid on busulfan-induced lipid peroxidation. INTRODUCTION: Free radicals are highly reactive molecules with odd number of electrons. They are constantly being generated in the body through various mechanisms and also being removed by endogenous antioxidant defense mechanism that acts by scavenging free radicals, decomposing peroxides and / or binding with pro-oxidant metal ion . Reactive oxygen species and other pro-oxidants cause the decomposition of 3 and 6 polyunsaturated fatty acids of membrane phospholipids leading to the formation of aldehydic end products including malondialdehyde (MDA), 4-hydroxy-2-nonenals (4HNE) and 4-hydroxy-2-alkenals (HAKs) of different chain length . In case of reduced or impaired defense mechanism and excess generation of free radicals that are not counter balanced by endogenous antioxidant defense exogenously administered antioxidants have been proven useful to overcome oxidative damage. Busulfan, an alkylating agent used extensively in bone marrow transplantation. But there are evidences that organ toxicity in bone marrow transplantation may in part be due to free radical damage . Ascorbic acid has versatile medicinal properties. It has been now established that besides its own physiological effects it has potential antioxidant property. Ascorbic acid has been reported to have protective role against cadmium induced thyroid dysfunction due to its antioxidant action . The protective effect of various antioxidants on anticancer drug-induced lipid peroxidation had been reported earlier by us . In continuation of ongoing search for antioxidants, the present work has been carried out in vitro to evaluate the antiperoxidative potential of ascorbic acid on busulfan-induced lipid peroxidation.