ABSTRACT
Toxicity to nonparenchymal cells can result in disruption of the hepatic microcirculation,
altered production of cytokines, and hepatic fibrosis. Many of the relevant insults
produce oxidative stress or toxic metabolites that require glutathione detoxification.
This article reviews the role of sinusoidal endothelial cell glutathione (GSH) in
reperfusion injury, cytomegalovirus infection, and hepatic venoocclusive disease.
The effects of oxidative stress and antioxidants on Kupffer cell production of cytokines
and, in particular, the potential benefit of antioxidants in the setting of reperfusion
injury, are discussed. Oxidative stress upregulates collagen gene expression by stellate
cells, and this is modulated by antioxidants. Current thinking on intrahepatic GSH
and cysteine homeostasis is discussed. Finally, I review the published data on nonparenchymal
GSH levels, glutathione S-transferase activity and isoenzyme pattern, and glutathione
peroxidase activity.
KEY WORDS
glutathione - endothelium - Kupffer cells - liver
