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


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.


CONCLUSIONS
All antidotes tested in this study against alpha-AMA were not effective in canine hepatocyte cultures.
Magdalan
Jan
J
Department of Pharmacology, Wroclaw Medical University, PL 50-345 Wroclaw, Poland. naladgam@op.pl
Ostrowska
Alina
A
Piotrowska
Aleksandra
A
Izykowska
Ilona
I
Nowak
Marcin
M
Szelag
Adam
A
Dziegiel
Piotr
P
D000111:Acetylcysteine / Q000627:therapeutic use*; D053959:Alpha-Amanitin / Q000506:poisoning*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000662:veterinary; D004285:Dogs; D008297:Male; D009145:Mushroom Poisoning / Q000188:drug therapy* / Q000662:veterinary; D010400:Penicillin G / Q000627:therapeutic use*; D000077385:Silybin; D012838:Silymarin / Q000627:therapeutic use
D053959:Alpha-Amanitin; D000931:Antidotes; D012838:Silymarin; D000077385:Silybin; D010400:Penicillin G; D000111:Acetylcysteine