GLUTATHIONE REGULATION IN RAT HEPATIC STELLATE CELLS - COMPARATIVE-STUDIES IN PRIMARY CULTURE AND IN LIVER-INJURY IN-VIVO

Lipid peroxidation accompanies many types of liver injury and is belie ved to promote liver fibrosis. Cellular antioxidants are likely to pla y an important role in modulating this process; however, little is kno wn about antioxidants in hepatic stellate cells, the major collagen-pr oducing cells of liver. In this study, we measured glutathione homeost asis in stellate cells isolated from rat liver. Glutathione, measured by HPLC in stellate cell homogenates, increased significantly when the cells were plated in primary culture. The rise in glutathione coincid ed with pretranslational up-regulation of the synthetic enzyme gamma-g lutamylcysteine synthetase (GCS). Additional experiments were performe d to determine whether stellate cell glutathione and GCS are similarly altered during liver injury in vivo. Two types of hepatic insults, na mely, bile duct ligation (8 days) and carbon tetrachloride treatment ( 4 weeks), failed to provoke an increase in either stellate cell glutat hione or GCS. This disparate behavior of stellate cells in culture and in vivo is unusual; the data suggest that stellate cells might respon d variably to oxidants depending on their glutathione status. (C) 1997 Elsevier Science Inc.