Resveratrol attenuates hepatotoxicity of rats exposed to arsenic trioxide

Arsenic trioxide (As2O3) is an environmental pollutant and potent toxicant to humans. However, it also shows substantial anti-cancer activity in individuals with acute promyelocytic leukemia (APL). Unfortunately, As2O3-treated leukemia patients suffer hepatotoxicity. Resveratrol has been demonstrated to have efficient antioxidant and antineoplastic activities. The study that how As2O3 in combination with resveratrol affects hepatotoxicity and arsenic accumulation in the liver is lacking, and the present study tackles this question. Wistar rats were injected with 3 mg/kg As2O3 on alternate days; resveratrol (8 mg/kg) was administered 1 h before As2O3. Rats were killed on the 8th day to determine histological liver damage, the antioxidant enzymes in serum, the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and arsenic accumulation in the liver. In the resveratrol + As2O3 group, activities of superoxide dismutase, catalase in serum and GSH/GSSG were significantly increased, histopathological effects were reduced, and arsenic accumulation markedly decreased in the liver, compared with the As2O3-treated group. Thus, resveratrol attenuated As2O3-induced hepatotoxicity by decreasing oxidative stress and arsenic accumulation in the liver. These data suggest that use of resveratrol as post-remission therapy of APL and adjunctive therapy in patients with chronic exposure to arsenic may decrease arsenic hepatotoxicity.