Failure of benzylpenicillin, N-acetylcysteine and silibinin to reduce alpha-amanitin hepatotoxicity

In Vivo. 2009 May-Jun;23(3):393-9.

Abstract

Background: Intoxications caused by amanitin-containing mushrooms represent an unresolved problem in clinical toxicology. The objective of this study was a comparative evaluation of benzylpenicillin (Bp), acetylcysteine (ACC) and silibinin (Sil) efficacy as antidotes in hepatocytes intoxicated with alpha-amanitin (alpha-AMA).

Materials and methods: All experiments were performed on cultured canine hepatocytes. Cytotoxicity evaluation of cultured cells (MTT assay, extracellular lactate dehydrogenase activity) was performed at 12, 24 and 48 h of exposure to alpha-AMA and/or antidotes.

Results: Following 24 and 48 h exposure there was a significant decline of hepatocyte viability and an increase of lactate dehydrogenase activity in groups exposed to alpha-AMA and in groups exposed simultaneously to alpha-AMA and antidotes. Moreover, hepatocyte viability and lactate dehydrogenase activity in all these groups were similar. Administration of studied antidotes without alpha-AMA, was not associated with any adverse effects in hepatocytes.

Conclusion: All antidotes tested in this study against alpha-AMA were not effective in canine hepatocyte cultures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Alpha-Amanitin / poisoning*
  • Animals
  • Antidotes / therapeutic use*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / veterinary
  • Dogs
  • Male
  • Mushroom Poisoning / drug therapy*
  • Mushroom Poisoning / veterinary
  • Penicillin G / therapeutic use*
  • Silybin
  • Silymarin / therapeutic use

Substances

  • Alpha-Amanitin
  • Antidotes
  • Silymarin
  • Silybin
  • Penicillin G
  • Acetylcysteine