The effects of resveratrol on SIRT2, SIRT3 expression levels and oxidative DNA damage in fumonisin-induced hepatotoxicity in BALB/c mice

Abstract

Oxidative stress, which is characterized by disruption of the oxidant/antioxidant balance, causes pathological processes, including toxicities induced by certain mycotoxins. The present study was designed to investigate the effects of resveratrol on sirtuin deacetylases (SIRT2 and SIRT3), nitric oxide (NO), reduced glutathione (GSH) and malondialdehyde (MDA) in fumonisin B1-induced hepatotoxicity. Regarding the experimental design, forty BALB/c mice were divided into four groups corresponding to the control, resveratrol (10 mg/kg, i.p), fumonisin B1 (2.25 mg/kg, i.p) and resveratrol + fumonisin B1 (10 mg/kg + 2.25 mg/kg) groups. At the end of the 14 day-treatment, expression levels of SIRT2 and SIRT3 protein in the serum and liver were revealed by western blotting and antioxidant/oxidant activity analysis. SIRT2 and SIRT3 expression levels in the liver were significantly decreased by fumonisin B1 in comparison to the control. However, resveratrol supplementation coupled with fumonisin B1 increased the expression levels of SIRT2 and SIRT3, in relation to the fumonisin B1 treatments alone, but did not exhibit significant differences from those of the control group. As substantial indicators of stress and damage, the 8-OH-2-deoxyguanosine, NO and MDA levels of the liver tissue were assayed, and were higher in the fumonisin B1-treated groups, in relation to the control. As expected, resveratrol treatment significantly reduced the levels of NO and MDA in comparison to the fumonisin B1 treatments alone. Also, resveratrol attenuated the liver 8-OH-2- deoxyguanosine levels in the resveratrol + fumonisin B1 group. In conclusion, the findings revealed that resveratrol might possess protective effects against fumonisin-induced hepatotoxicity through modulation of the expression of sirtuin proteins, and by protecting the cell from oxidative/nitrosative stress.