Trolox mitigates fibrosis in a bile duct ligation model

Several studies suggest that free radicals may play a role in cholestatic liver injury. The aim of this work was to evaluate the role of trolox in chronic bile duct ligation (BDL). Liver injury was induced by 28-day BDL to male Wistar rats. Animals were divided in four groups of six rats. Trolox was administered daily (50 mg/kg, p.o.). Alanine aminotransferase (ALT) was quantified in serum. Fibrosis was assessed measuring liver hydroxyproline content. Reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxidation, catalase (CAT), and glutathione peroxidase (GPx) activities were measured in liver. Transforming growth factor-β (TGF-β), interleukin-6 (IL-6), and interleukin-10 (IL-10) were determined by western blot and quantified densitometrically. Our results show that trolox treatment in BDL rats prevented the increase in ALT. Collagen was increased by chronic BDL, but trolox administration preserved the normal collagen concentration. BDL produced high levels of the cytokine TGF-β1, IL-6, and IL-10 levels. Trolox administration was effective to partially prevent the increase of TGF-β1 and IL-6, and it was able to further augment the levels of IL-10. Oxidative stress (assessed by lipid peroxidation and liver glutathione content) was increased by BDL; this process was normalized by trolox. The activities of CAT and GPx were altered by BDL, and trolox prevented these events. We found that there is a close relationship between cholestatic liver damage and oxidative stress generation, and this was effectively prevented by trolox. Our study shows that the beneficial effects of trolox are because of its important antioxidant and immunomodulatory properties.