Glutathione status in liver and plasma during development of biliary cirrhosis after bile duct ligation

We do not know much about the changes that occur in reduced (GSH) and oxidi zed (GSSG) glutathione in the development of liver cirrhosis. There fore, w e investigated the glutathione redox system during development of liver cir rhosis after bile-duct ligation in rats. We compared the GSH and GSSG conte nt of liver and plasma between bile-duct-ligated rats and sham-operated con trols 6 and 24 h and 5, 15, 23, and 38 days after operation. Compared to co n controls (x+/-SD: 6.07+/-0.52 mu mol/g wet wt.), liver GSH significantly increased 24 h (+37%) and 5 days (+53%) after bile-duct ligation. Thereafte r, GSH continuously declined to 4.25+/-0.64 mu mol/g (-31%; P<0.001) at the end of the observation period after 38 days. The GSH turnover in fi-day bi le-duct-ligated rats with high GSH concentrations was not significantly dif ferent than in sham-operated controls (16 nmol/min per g after bile-duct li gation and 15 nmol/min per g in controls). GSSG (211+/-42 nmol/g wet wt. in controls) was significantly lower 6 and 24 h after bile-duct ligation (-34 % and -43%, respectively). Thereafter, GSSG increased and was about 100% hi gher than in controls after 23 and 38 days. The relation of GSSG to GSH in liver continuously increased from 3.4 to 20.5% after bile-duct ligation. Th e course of plasma GSH (9.57+/-0.79 mu mol/l) paralleled hepatic GSH on a l ower level: +14% at day 5, -41% at day 15 and -51% at the end of the observ ation period. Plasma GSSG (0.99+/-0.31 mu mol/l) was inversely related to l iver GSSG: there were increased concentrations early after bile duct ligati on (day 5: +91%) and reduced concentrations (-44%) at the end of the observ ation period. Dynamic changes of the glutathione status occur in the develo pment of liver cirrhosis after bile-duct ligation. These changes are consis tent with increased oxidative stress in the liver and a deficit of transpor ting GSSG from the cells into plasma.