Evidence for potential application of zinc as an antidote to acetaminophen-induced hepatotoxicity.
The therapeutic application of zinc sulphate as an antidote to acetaminophen overdose was examined in ICR mice. Hepatotoxicity was induced by a single oral dose of acetaminophen (750 mg/kg). Various treatments (normal saline, 15 or 30 mg/kg zinc sulphate, 150 mg/kg N-acetylcysteine, 15 mg/kg zinc sulphate + 150 mg/kg N-acetylcysteine) were given i.p. 1 h after acetaminophen overdose. Serum alanine aminotransferase, hepatic glutathione and malondialdehyde levels were measured before experiments and at various intervals after the administration of acetaminophen. Serum acetaminophen levels were also measured at different different intervals. Zinc sulphate showed protection by dose-dependently reducing alanine aminotransferase and malondialdehyde levels. The drug also partially prevented the depletion of hepatic glutathione. These effects were not as good as those of N-acetylcysteine. However, the combination of zinc sulphate with N-acetylcysteine produced even better protective effects. Furthermore, drug treatments did not affect serum acetaminophen levels. It is concluded that both drugs attenuate acetaminophen-induced hepatic toxicity, and the action is likely to be mediated through replenishment of hepatic glutathione levels. The use of zinc sulphate alone or in combination with N-acetylcysteine could be another alternative for the treatment of acetaminophen overdose in view of possible side effects produced by N-acetylcysteine.
Woo
P C
PC
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong.
Kaan
S K
SK
Cho
C H
CH
D000082:Acetaminophen / Q000097:blood / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D013431:Sulfates / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology*; D019287:Zinc Sulfate
D000931:Antidotes; D013431:Sulfates; D017967:Zinc Compounds; D000082:Acetaminophen; D008315:Malondialdehyde; D019287:Zinc Sulfate; D000410:Alanine Transaminase; D005978:Glutathione; D000111:Acetylcysteine