Studies on the mechanism of glutathione prevention of carbon tetrachloride-induced liver injury.

The prior administration of reduced glutathione (GSH) partially prevents carbon tetrachloride (CCl4)-induced liver necrosis observed at 24 h after administration of the hepatotoxin. No prevention occurs when observations are made at 72 h. GSH pretreatment does not significantly modify the intensity of the covalent binding of CCl4 reactive metabolites to microsomal lipids or the intensity of the CCl4-induced lipid peroxidation process at either 1, 3 or 6 h after poisoning. GSH administration does not significantly prevent CCl4-induced cytochrome P-450 destruction or glucose 6 phosphatase activity depression. Pretreatment with GSH does not significantly modify the levels of CCl4 or i.p. administered CCl4 reaching the liver at 1, 3 or 6 h after intoxication. Pretreatment with GSH significantly prevents CCl4-induced decreases in body temperature. Results are interpreted as suggesting that GSH prevents CCl4-induced liver necrosis by changing the liver cell's response to injury rather than by modification of early events of the process such as lipid peroxidation or covalent binding of reactive metabolites.