POTENTIATION OF ACETAMINOPHEN HEPATOTOXICITY BY ACUTE PHYSICAL EXERCISE IN RATS

Effects of acute physical exercise on the acetaminophen-induced hepato toxicity were examined in adult female rats. Rats were forced to move at a speed of 10 m/min for 2 hr in a rotating cage. Immediately follow ing the exercise bout rats were treated with acetaminophen (APAP; 700 mg/kg, ip). The physical exercise enhanced the hepatotoxicity of APAP as shown by increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities measured 24 hr following the treatme nt. A significant decrease in hepatic glutathione (GSH) was observed i n the rats forced to exercise suggesting that the enhancement of APAP hepatotoxicity was associated with the depression of this endogenous t ripeptide. The role of adrenergic stimulation in the exercise-induced hepatic GSH depression was examined by pretreating the animals with a receptor specific adrenergic antagonist, such as prazosin HCl (15 mg/k g, ip), propranolol HCl (15 mg/kg, ip), and yohimbine HCl (15 mg/kg, i p) 15 min prior to the exercise bout, but neither of the antagonists p revented the GSH depression. Administration of alpha-tocopherol acetat e (450 mg/kg/day for 3 days and 150 mg/kg on day 4, ip) did not affect the exercise-induced GSH depression or lipid peroxidation in liver ho mogenates as determined by increases in malondialdehyde formation. The se results suggest that neither adrenergic stimulation nor oxidative s tress plays a significant role in the enhancement of APAP hepatotoxici ty and hepatic GSH depression induced by acute physical exercise.