Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of Nrf2 pathway

Hepatic oxidative stress, as one important mechanism of cadmium (Cd)-induced hepatic toxicity, could, as known, be ameliorated by vitamin E (VE). However, the underlying mechanism remains to be elucidated. To investigate whether the antioxidant vitamin E can protect against Cd-induced sub-chronic liver injury associated with oxidative stress and nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway, male Sprague-Dawley rats (nine-week-old) were randomly divided into four groups (eight rats/group), namely, control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl2) and VE+Cd (100 mg/kg VE+5 mg/kg CdCl2), and received intragastric administration of Cd and/or VE for four weeks. Cd-exposure alone resulted in reduced liver weight, liver histological alteration and oxidative stress, accumulation of Cd in the liver, elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO-1, GCLC, GCLM and GST). However, the co-treatment of Cd and VE significantly ameliorated the changes mentioned above, and promoted the expression of genes and proteins of Nrf2 pathway related molecules in comparison to the Cd-exposure alone. Our results indicate that the protective effect of VE against Cd-induced sub-chronic hepatic damage in rats is associated with the inhibition of oxidative stress and activation of Nrf2 pathway.