Toxicity and toxicokinetics of Amanita exitialis in beagle dogs

In this study, the toxicology of A. exitialis, a lethal mushroom found in China, and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which they were assessed for signs of toxicity, as well as biochemical and pathological changes. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to assay the peptide toxins. The total peptide toxins in A. exitialis was 3482.6 +/- 124.94 mg/kg. The beagles showed signs of toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A. exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in plasma, as well as prothrombin time and activated partial thromboplastin time peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting the capsules. Additionally, liver histopathological examinations showed hemorrhagic necrosis of hepatocytes. alpha-Amanitin, beta-amanitin, and phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis was ingested. A long latency period (12-24 h post A. exitialis ingestion) was observed in the dogs before the onset of gastrointestinal symptoms. There was acute liver damage thereafter. Gastric lavage and enhanced plasma clearance methods such as hemodialysis, hemoperfusion, or plasma exchange may be ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion. Enhanced excretion of amatoxins in urine could be effective within 2 days after ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more than 90% of the total urine excretion. (C) 2018 Elsevier Ltd. All rights reserved.