Mushrooms, Amatoxin-Type
Amatoxins are a group of highly toxic peptides found in several species of mushrooms, including Amanita phalloides, Amanita virosa, Amanita bisporigera, Amanita ocreata, Amanita verna, Galerina autumnalis, Galerina marginata, and some species of Lepiota and Conocybe. This category of mushrooms is responsible for more than 90% of mushroom deaths worldwide.
This group is also referred to as cyclopeptide-containing mushrooms. The three cyclopeptides are amatoxin, phallotoxin, and virotoxin. Amatoxins, principally alpha-amanitin, are the most toxic and responsible for hepatic and renal toxicity. Phallotoxins are not well absorbed and cause GI symptoms. Virotoxins are not implicated in human poisoning.
Mechanism of toxicity. Amatoxins are highly stable and resistant to heat and are not removed by any form of cooking. They bind to DNA-dependent RNA polymerase II and inhibit the elongation essential to transcription. The result is a decrease in mRNA that causes an arrest of protein synthesis and cell death. Metabolically active tissue dependent on high rates of protein synthesis, such as cells of the GI tract, hepatocytes, and the proximal convoluted tubules of the kidney, are disproportionately affected. Cellular damage has also been found in the pancreas, adrenal glands, and testes.
Pharmacokinetics. Amatoxins are readily absorbed from the intestine and transported across the hepatocytes by bile transport carriers. About 60% undergo enterohepatic recirculation. They have limited protein binding and are eliminated in urine, vomitus, and feces. Toxins are detectable in urine within 90–120 minutes after ingestion. No metabolites of amatoxin have been detected. The half-life in humans is unknown, but there is a rapid decrease in serum levels, with detection of toxin unlikely after 36 hours.
Toxic dose. Amatoxins are among the most potent toxins known; the minimum lethal dose is about 0.1 mg/kg. One Amanita phalloides cap may contain 10–15 mg. In contrast, Galerina species contain far less toxin; 15–20 caps would be a fatal dose for an adult.
Clinical presentation.
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