ALTERED LIPID-PEROXIDATION GLUTATHIONE RATIO IN EXPERIMENTAL EXTRAHEPATIC CHOLESTASIS

1. Lipid peroxidation can occur in the presence of a cellular antioxid ant-oxidant imbalance, but the role of lipid peroxides in cholestasis is not well understood. 2. This study was undertaken in order to: (i) evaluate the behaviour of a product of lipid peroxidation (thiobarbitu ric acid-reactive species), and of an important antioxidant tripeptide , reduced glutathione, in the course of experimental extrahepatic chol estasis; and (ii) ascertain whether there was a link between this aspe ct and the alterations in liver morphology. 3. Forty-five male Sprague -Dawley rats (250-300 g) were double bile duct ligated and followed fr om 1 to 28 days. At the end of each experimental period, blood and liv er samples were collected for thiobarbituric acid-reactive species and glutathione determinations. 4. Bile duct ligated rats showed a marked increase in liver weight which was related to cholestasis duration an d to some anatomical alterations such as bile duct proliferation and d ilation and liver fibrosis (periportal, perivenular, perineoductular a nd parenchymal). 5. An increase in serum lipid peroxidation was also o bserved but this was not linked to hepatic thiobarbituric acid-reactiv e species. Erythrocyte and hepatic glutathione decreased in relation t o cholestasis duration. Serum lipid peroxides and erythrocyte glutathi one were correlated with liver cell necrosis. 6. In conclusion, experi mental extrahepatic cholestasis determines bile duct proliferation and fibrosis, the degree of which is directly related to the duration of cholestasis itself and to liver cell necrotic phenomena. Furthermore, extrahepatic cholestasis is associated with increased lipid peroxide f ormation and with a depletion of reduced glutathione both in the liver and in the erythrocytes. The alteration in the oxidative balance may be a contributory factor in necrotic liver cell phenomena.