Protection from acetaminophen-induced liver damage by the synergistic action of low doses of the poly(ADP-ribose) polymerase-inhibitor nicotinamide and the antioxidant N-acetylcysteine or the amino acid L-methionine

1. An array of therapeutically used analgetic and antirheumatic drugs cause severe liver damage, The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions and of antioxidants in analgesic-induced hepatic injury. 2. Male NMRI mice were treated PO with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. 3. The acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited in a dose-dependent manner, when mice were injected additionally either with increasing amounts (from (25 mg/kg to 100 mg/kg TP) of the PARP-inhibitor nicotinamide, with increasing amounts (from 25 mg/kg to 100 mg/kg IF) of the antioxidant N-acetylcysteine, or with increasing amounts (from 50 mg/kg to 300 mg/kg IF) of the amino acid L-methionine. 4. A combination of both nicotinamide and N-acetylcysteine (at the low dose of 12.5 mg/kg IP each) results in a complete protection from acetaminophen induced release of GOT and GPT from injured liver cells. 5. A combination of both L-methionine and N-acetylcysteine or nicotinamide (at the low dose of 12.5 mg/kg IP each) resulted also in complete protection from acetaminophen-induced release of GOT and GPT. Copyright (C) 1997 Elsevier Science Inc.