Resveratrol protects against arsenic trioxide-induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress

Arsenic trioxide (As2O3) is an environmental toxicant and a potent antineoplastic agent. Exposure to arsenic causes renal cancer. Resveratrol is a well-known polyphenolic compound that is reported to reduce As2O3-induced cardiotoxicity. The present study aimed to investigate the effect of resveratrol on As2O3-induced nephrotoxicity and arsenic metabolism. Chinese Dragon-Li cats were injected with 1 mg/kg As2O3 on alternate days; resveratrol (3 mg/kg) was administered via the forearm vein 1 h before the As2O3 treatment. On the sixth day, the cats were killed to determine the histological renal damage, renal function, the accumulation of arsenic, and antioxidant activities in the kidney. Urine samples were taken for arsenic speciation. In the resveratrol + As2O3-treated group, activities of glutathione peroxidase, catalase, and superoxide dismutase, the ratio of reduced glutathione to oxidized glutathione, the total arsenic concentrations, and the percentage of methylated arsenic in urine were significantly increased. The concentrations of renal malondialdehyde, reactive oxygen species, 8-hydroxydeoxyguanosine, serum creatinine, blood urea nitrogen, and renal arsenic accumulation were significantly decreased and reduced renal morphologic injury was observed compared with the As2O3-treated group. These results demonstrate that resveratrol could significantly scavenge reactive oxygen species, inhibit As2O3-induced oxidative damage, and significantly attenuate the accumulation of arsenic in renal tissues by facilitating As2O3 metabolism. These data suggest that use of resveratrol as postremission therapy for acute promyelocytic leukemia as well as adjunctive therapy in patients with exposure to arsenic may decrease arsenic nephrotoxicity.