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 i.p.) of the PARP-inhibitor nicotinamide, with increasing amounts (from 25 mg/kg to 100 mg/kg i.p.) of the antioxidant N-acetylcysteine, or with increasing amounts (from 50 mg/kg to 300 mg/kg i.p.) of the amino acid L-methionine. 4. A combination of both nicotinamide and N-acetylcysteine (at the low dose of 12.5 mg/kg i.p. 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.
Kröger
H
H
Deutsches Rheumaforschungszentrum Berlin, Germany.
Dietrich
A
A
Ohde
M
M
Lange
R
R
Ehrlich
W
W
Kurpisz
M
M
D000082:Acetaminophen / Q000633:toxicity; D000111:Acetylcysteine / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009536:Niacinamide / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; D000082:Acetaminophen; D008715:Methionine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine