Glutathione defense in non-parenchymal cells.
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.
DeLeve
L D
LD
Division of Gastrointestinal and Liver Disease and the USC Research Center for Liver Disease, University of Southern California School of Medicine, Los Angeles 90033, USA.
D000818:Animals; D003586:Cytomegalovirus Infections / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006504:Hepatic Veno-Occlusive Disease / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism
D005978:Glutathione