OXIDATIVE STRESS BY ACUTE ACETAMINOPHEN ADMINISTRATION IN MOUSE-LIVER

Acetaminophen was given to mice at a single dose of 375 mg/kg. In situ liver chemiluminescence, H2O2 steady-state concentration, and the liv er concentrations of total and oxidized glutathione were measured 15, 30, and 60 min after acetaminophen administration. Increases of 145% a nd 72% in spontaneous chemiluminescence and H2O2 concentration were ob served 15 min after the injection, respectively. Total glutathione was decreased by acetaminophen administration at all the times studied. T he maximal decrease, 83%, was found 60 min postinjection. The ratio GS H/GSSG was found significantly decreased at all the times studied. Mic rosomal superoxide production was increased by 2.4-fold by addition of acetaminophen. The activities of the antioxidant enzymes superoxide d ismutase, catalase, and glutathione peroxidase were determined. Catala se was slightly inhibited (30%) 15 min after acetaminophen administrat ion. No significant changes were found in superoxide dismutase activit y. Se and non-Se glutathione peroxidase activities were decreased by 4 0% and 53% respectively, 15 min after acetaminophen administration. Th e decrease in catalase and glutathione peroxidase would result in an i ncreased steady state level of H2O2 and hydroperoxides, contributing t o cell injury. Damaged hepatocytes were observed, and severe lesions a nd necrosis appeared 60 min after acetaminophen administration. Our re sults indicate the occurrence of oxidative stress as a possible mechan ism for acetaminophen-induced hepatotoxicity.