Role of glutathione, lipid peroxidation and antioxidants on acute bile-duct obstruction in the rat

The aim of this work was to evaluate the role of lipid peroxidation and glu tathione on liver damage induced by 7-day biliary obstruction in the rat. M ale Wistar rats were bile-duct-ligated and divided in groups of 10 animals. Groups received vitamin E (400 IU/rat, p.o., daily) or trolox (50 mg/kg, p .o., daily) or both. Lipid peroxidation increased significantly in the live rs of bile-duct-ligated rats. Vitamin E and trolox prevented lipid peroxida tion. GSH was oxidized in the BDL group and the GSH/GSSG ratio decreased as a consequence. However, total glutathione content increased in liver and b lood indicating a possible induction in de novo synthesis of GSH. Antioxida nts preserved the normal GSH/GSSG ratio. Despite the observation that antio xidants verted lipid peroxidation and oxidation of GSH, liver injury (as as sessed by serum enzyme activities, bilirubin concentration, liver glycogen content and histology) was not affected by the treatments. These results su ggest that drugs that inhibit lipid peroxidation and oxidation of glutathio ne have no effect on conventional biochemical markers of liver injury and o n liver histology of bile-duct-ligated rats for 7 days. It seems more likel y that the detergent action of bile salts is responsible for solubilization of plasma membranes and cell death, which in turn may lead to oxidative st ress, GSH oxidation and lipid peroxidation. (C) 1999 Elsevier Science B.V. All rights reserved.