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