Biochemical events associated with ligation of the common bile duct in Wistar rats

Oxygen free radicals have been implicated as mediators of tissue injury in a variety of diseases. We investigated the role of oxidative injury and oxygen free radical scavengers in liver cell injury associated with obstructive jaundice in Wistar rats. Bile duct ligation for 4 or 7 days led to a decrease in both vitamin E and A in the plasma and liver of male Wistar rats, indicating the malabsorption of lipid-soluble vitamins. Serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase activities were increased in the bile-duct-ligated rats. Furthermore, marked increases in lipid peroxide and oxidized glutathione levels indicated cholestatic liver injury. The antioxidant defense system was impaired, as shown by decreases in reduced glutathione and in the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase. Moreover, these high lipid peroxide levels and low levels of antioxidants correlated with the severity of jaundice. After releasing the bile duct ligation, levels of bilirubin, lipid peroxide and oxidized glutathione declined, while the levels of vitamin E and A, reduced glutathione, and the activities of GSH-Px increased, indicating an improvement in liver function. These findings suggest that lipid peroxidation is associated with the pathogenesis of liver damage in animals with bile duct ligation. Meanwhile, free oxygen radical scavengers are reduced in the bile-duct-ligated rats, thereby increasing the susceptibility of the liver to injury by oxygen-derived free radicals.