The impact of hepatic xanthine oxidase and xanthine dehydrogenase activities on liver function in chronic cholestasis

Activities of hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XD) , serum liver enzymes, and reduced glutathione (GSH) were determined in liv ers of chronic cholestatic rats. The common bile duct was ligated (CBDL) an d rats were randomized to either an untreated group or to treatment with al lopurinol, a competitive XO inhibitor, or received a tungsten-supplemented diet to inactivate XO and XD, or received antioxidants vitamin C and vitami n E. One group underwent only sham laparotomy. After 4 weeks, in untreated CBDL animals serum aspartate aminotransferase and bilirubin concentrations were significantly elevated and hepatic GSH was significantly decreased whe n compared with the sham-operated group. Histochemical and enzymatic determ inations of XD and XO showed a significant increase in hepatic XO activity after CBDL. Treatment with allopurinol and a tungsten-supplemented, molybde num-free diet significantly attenuated serum liver enzymes, hepatic XO acti vity, and improved hepatic GSH levels, whereas vitamins C and E had a posit ive effect only on hepatic GSH levels. Our results support the hypothesis t hat cholestasis-induced hepatocellular injury is partially triggered by oxi dative processes derived from increased hepatic XO activity. Inhibition and inactivation of XO exerts a hepatocellular protective effect in chronic ch olestasis.