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

Abstract

We do not know much about the changes that occur in reduced (GSH) and oxidized (GSSG) glutathione in the development of liver cirrhosis. Therefore, we investigated the glutathione redox system during development of liver cirrhosis after bile-duct ligation in rats. We compared the GSH and GSSG content of liver and plasma between bile-duct-ligated rats and sham-operated controls 6 and 24 h and 5, 15, 23, and 38 days after operation. Compared to controls (x±SD: 6.07±0.52 μmol/g wet wt.), liver GSH significantly increased 24 h (+37%) and 5 days (+53%) after bile-duct ligation. Thereafter, GSH continuously declined to 4.25±0.64 μmol/g (−31%; P<0.001) at the end of the observation period after 38 days. The GSH turnover in 5-day bile-duct-ligated rats with high GSH concentrations was not significantly different than in shamoperated controls (16 nmol/min per g after bile-duct ligation 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% higher 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. The course of plasma GSH (9.57±0.79 μmol/l) paralleled hepatic GSH on a lower level: +14% at day 5, −41% at day 15 and −51% at the end of the observation period. Plasma GSSG (0.99±0.31 μmol/l) was inversely related to liver GSSG: there were increased concentrations early after bile duct ligation (day 5: +91%) and reduced concentrations (−44%) at the end of the observation period. Dynamic changes of the glutathione status occur in the development of liver cirrhosis after bile-duct ligation. These changes are consistent with increased oxidative stress in the liver and a deficit of transporting GSSG from the cells into plasma.