Cimetidine protection against alpha-amanitin hepatotoxicity in mice: a potential model for the treatment of Amanita phalloides poisoning.
The ingestion of the mushroom Amanita phalloides is associated with hepatic necrosis appearing clinically two to three days after ingestion. The mechanism of this toxicity is unknown, and no reliable antidote is available. Because of the similarity of Amanita poisoning to other toxins affecting cytochrome P450, we investigated the use of cimetidine (as a P450 cytochrome inhibitor) as an antidote against a primary toxin of the mushroom alpha-amanitin. Mice injected with alpha-amanitin and given cimetidine either prophylactically or within six hours showed histologic protection from the hepatic damage seen in control mice. Control animals displayed significant mitochondrial changes when examined by electron-microscopy, while the mitochondria of the cimetidine-treated animals were preserved, suggesting a possible site for toxin action. Further trials will be necessary before treatment of human cases with cimetidine is indicated.
Schneider
S M
SM
Department of Internal Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
Borochovitz
D
D
Krenzelok
E P
EP
D000545:Amanita; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology / Q000627:therapeutic use*; D065607:Cytochrome P-450 Enzyme Inhibitors; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000648:ultrastructure; D008954:Models, Biological; D009145:Mushroom Poisoning / Q000188:drug therapy* / Q000473:pathology
D065607:Cytochrome P-450 Enzyme Inhibitors; D002927:Cimetidine