Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

Resveratrol (Rev) can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As(2)O(3)) is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As(2)O(3) are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As(2)O(3) treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As(2)O(3)-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As(2)O(3)-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As(2)O(3)-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As(2)O(3)-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As(2)O(3)-induced hepatotoxicity.