|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1992 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1991 : ¥1,400,000 (Direct Cost : ¥1,400,000)
The purpose of the present study was to investigate the roles of oxygen radicals and its scavenger, glutathione, in various types of hepatic injury.
Glutathione is an important factor that protects cells from radical attacks. We confirmed that vasopressin increased GSH efflux from the liver using perfused rat livers and isolated rat hepatocytes. This effect was inhibited by a specific inhibitor for V1 receptors. We also studied the effect of vasopressin on GSH efflux from Hep G2 cells, and found that protein kinase C as well as c-AMP dependent pathway, c-GMP dependent pathway, and Ca^<++> mobilization may be involved in vasopressin stimulated GSH efflux from Hep G2 cells. These findings suggest that hormones may play an important role in the defense against oxygen radical attacks, since GSH effluxed from the liver is transported to other organs through plasma.
In bile duct ligated rats, glutathione was increased in the liver and kidney. Lipid peroxidation assessed as TBA-reactive substances was also increased in the kidney. In this model, renal dysfunction was easily caused by ischemia-reperfusion or gentamicin, which was associated with a further increase in lipid perxidation. Thus, in obstructive jaundice, kidneys appear to be susceptible to stimuli that increase lipid peroxidation. In chronically iron-overloaded rats, lipid peroxidation in the liver was increased. Lipid peroxidation may be involved in liver dysfunction in hemochromatosis. Increased hepatic levels of 8- hydroxyguanosine may account for increased incidence of hepatocellular carconoma in hemochromatosis. In chronically cadmium-overloaded rats, GSH was increased in the liver and kidney whereas no changes were observed in lipid peroxidation in both organs.