Resveratrol Attenuates Aflatoxin B1-Induced ROS Formation and Increase of m6A RNA Methylation.

Aflatoxin B₁ (AFB₁) is one of the most dangerous mycotoxins in both humans and animals. Regulation of resveratrol is essential for the inhibition of AFB₁-induced oxidative stress and liver injury. Whether N⁶-methyladenosine (m⁶A) mRNA methylation participates in the crosstalk between resveratrol and AFB₁ is unclear. The objective of this study was to investigate the effects of AFB₁ and resveratrol in m⁶A RNA methylation and their crosstalk in the regulation of hepatic function in mice. Thirty-two C57BL/6J male mice were randomly assigned to a CON (basal diet), RES (basal diet + 500 mg/kg resveratrol), AFB₁ (basal diet + 600 μg/kg aflatoxin B₁), and ARE (basal diet + 500 mg/kg resveratrol and 600 μg/kg aflatoxin B₁) group for 4 weeks of feeding (n = 8/group). Briefly, redox status, apoptosis, and m⁶A modification in the liver were assessed. Compared to the CON group, the AFB₁ group showed increased activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), prevalent vacuolization and cell edema, abnormal redox status, imbalance apoptosis, and especially, the higher expression of cleaved-caspase-3 protein. On the contrary, resveratrol ameliorated adverse hepatic function, via increasing hepatic antioxidative capacity and inhibiting the expression of cleaved-caspase-3 protein. Importantly, we noted that reactive oxygen species (ROS) content could be responsible for the alterations of m⁶A modification. Compared to the CON group, the AFB₁ group elevated the ROS accumulation, which led to the augment in m⁶A modification, whereas dietary resveratrol supplementation decreased ROS, followed by the reduction of m⁶A levels. In conclusion, our findings indicated that resveratrol decreased AFB₁-induced ROS accumulation, consequently contributing to the alterations of m⁶A modification, and eventually impacting on the hepatic function.