Glutathione regulation in rat hepatic stellate cells: Comparative studies in primary culture and in liver injury in vivo

Abstract

Lipid peroxidation accompanies many types of liver injury and is believed to promote liver fibrosis. Cellular antioxidants are likely to play an important role in modulating this process; however, little is known about antioxidants in hepatic stellate cells, the major collagen-producing cells of liver. In this study, we measured glutathione homeostasis 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 coincided with pretranslational up-regulation of the synthetic enzyme γ-glutamylcysteine synthetase (GCS). Additional experiments were performed to determine whether stellate cell glutathione and GCS are similarly altered during liver injury in vivo. Two types of hepatic insults, namely, bile duct ligation (8 days) and carbon tetrachloride treatment (4 weeks), failed to provoke an increase in either stellate cell glutathione or GCS. This disparate behavior of stellate cells in culture and in vivo is unusual; the data suggest that stellate cells might respond variably to oxidants depending on their glutathione status.