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“The only thing necessary for these diseases to the triumph is for good people and governments to do nothing.”


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.

    

Author: KROGER H, DEUTSCH RHEUMAFORSCHUNGSZENTRUM BERLIN, MONBIJOUSTR 2, D-10117 BERLIN, GERMANY Source: GENERAL PHARMACOLOGY 1997 FEB;28(2):257-263