Oxidative stress by acute acetaminophen administration in mouse liver

LORES ARNAIZ, S.; LLESUY, S.; CUTRIN, J.C. ; BOVERIS, A.

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Año: 1995 vol. 19 p. 303 - 310

0891-5849

Acetaminophen was given to mice at a single dose of 375 mg/kg. In situ liver chemiluminescence, H202 steadystate concentration, and the liver concentrations of total and oxidized glutathione were measured 15, 30, and 60 min after acetaminophen administration. Increases of 145% and 72% in spontaneous chemiluminescence and H202 concentration were observed 15 rain after the injection, respectively. Total glutathione was decreased by acetaminophen administration at all the times studied. The maximal decrease, 83%, was found 60 rain postinjection. The ratio GSH/GSSG was found significantly decreased at all the times studied. Microsomal superoxide production was increased by 2.4-fold by addition of acetaminophen. The activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were determined. Catalase was slightly inhibited (30%) 15 rain after acetaminophen administration. No significant changes were found in superoxide dismutase activity. Se and non-Se glutathione peroxidase activities were decreased by 40% and 53% respectively, 15 rain after acetaminophen administration. The decrease in catalase and glutathione peroxidase would result in an increased steady state level of H202 and hydroperoxides, contributing to ceU injury. Damaged hepatocytes were observed, and severe lesions and necrosis appeared 60 rain after acetaminophen administration. Our results indicate the occurrence of oxidative stress as a possible mechanism for acetaminophen-induced hepatotoxicity.