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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.

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