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• W2159165907 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 α-amanitin (α-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 α-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 α-AMA and in groups exposed simultaneously to α-AMA and antidotes. Moreover, hepatocyte viability and lactate dehydrogenase activity in all these groups were similar. Administration of studied antidotes without α-AMA, was not associated with any adverse effects in hepatocytes. Conclusion: All antidotes tested in this study against α-AMA were not effective in canine hepatocyte cultures. Exposure to mushrooms containing amatoxins is fairly common all over the world (1-6). Currently there are more than 30 known amatoxin-producing species belonging to the genera Amanita, Galerina and Lepiota. The toadstool death cap (Amanita phalloides) and its subspecies, destroying angel (Amanita virosa) and death angel (Amanita verna) are responsible for nearly 95% of all fatal mushroom poisonings (6). High mortality rate in Amanita phalloides intoxications is principally a result of the acute liver failure following significant hepatocyte damage due to hepatocellular uptake of α-amanitin (α-AMA), the major amatoxin (6-9). Severe intoxications caused by amanitin- containing mushrooms represent an unresolved problem in clinical toxicology since no specific and fully efficient antidote is readily available. Several substances widely used in the past to treat mushroom poisonings (steroids, cimetidine, thioctic acid) are documented to be completely ineffective. Moreover, a retrospective analysis revealed that the most often currently used antidote - benzylpenicillin (Bp) shows poor clinical efficacy (1). Overall results of this meta-analysis indicate that silibinin (Sil) or acetylcysteine (ACC) are found to be more effective in mushroom poisoning therapy in humans. However, ACC, Sil and Bp were not effective in limiting hepatic injury after α-AMA poisoning in a murine model (10). Since clinical course and symptoms of amanitin intoxication in dogs are almost identical to those seen in humans, a concept of the treatment of this type of toxicity can be studied in a canine hepatocyte model (11-14). The objective of this study was a comparative evaluation of ACC, Bp and Sil efficacy in canine hepatocytes intoxicated with α-AMA." @default.
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• W2159165907 date "2009-05-01" @default.
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• W2159165907 title "Failure of Benzylpenicillin, N-Acetylcysteine and Silibinin to Reduce α-Amanitin Hepatotoxicity" @default.
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