Use of Amifostine, a Novel Cytoprotective, in α-Amanitin Poisoning

Background. Mortality from ingestions of the mushroom Amanita phalloides remains as high as 20–40% with many surviving patients requiring liver transplantation. A variety of treatments for Amanita ingestion have been evaluated, yet other than supportive measures, no effective therapy has been identified. In addition, an antidote for Amanita toxicity may not be practical due to delayed patient presentation. The drug amifostine was proposed to potentially improve survival from α-amanitin toxicity by conferring cytoprotective effects on hepatocytes at risk for cell death. Amifostine is used as a radio- and chemo-protective agent. It protects against lipoperoxidation, interferes with the cross-linking of DNA, and may act by other mechanisms yet to be identified, making it attractive for potentially attenuating ongoing hepatic necrosis. It has not previously been studied in a toxicologic model. Study Objective. To determine whether amifostine is an effective postexposure therapy for α-amanitin, the primary let...