Amanita phalloides mushroom poisoning

The skin often appears flushed, hot, and dry in poisoning with atropine and other antimuscarinics. Excessive sweating occurs with organophosphates, nicotine, and sympathomimetic drugs. Cyanosis may be caused by hypoxemia or by methemoglobinemia. Icterus may suggest hepatic necrosis due to acetaminophen or Amanita phalloides mushroom poisoning. 

Although milk thistle has not been confirmed as an antidote following acute exposure to liver toxins in humans, parenteral silybin is nevertheless marketed and used in Europe as an antidote in Amanita phalloides mushroom poisoning. This use is based on favorable outcomes reported in case-control studies. 

Pharmacology In vitro studies show that milk thistle reduces lipid peroxidation, scavenges free radicals, enhances superoxide dismutase, inhibits formation of leukotrienes, and increases hepatocyte RNA polymerase activity. In animal models, milk thistle protects against liver injury caused by alcohol, acetaminophen, and amanita mushrooms. The outcomes of clinical trials in patients with liver disease caused by alcohol have been mixed. In viral hepatitis and liver injury caused by amanita mushrooms, results of clinical trials have been mainly favorable. A commercial preparation of silybin (an isomer of silymarin) is available in some countries as an antidote to Amanita phalloides mushroom poisoning. 

B. Intravenous dosing for Amanita phalloides mushroom poisoning is 20-50 mg/kg over 24 hours divided into four infusions. Each intravenous dose is administered over 2 hours. Parenteral milk thistle extract is not available in the United States. 

B. Parenteral. A water-soluble derivative of silybinin is used parenterally in Europe for cases of Amanita phalloides mushroom poisoning. Intravenous formulations of milk thistle extract are not available in the United States. 

Figure 28.16. RNA Polymerase Poison. Amanita phalloides, a poisonous mushroom that produces a-amanitin. [After G. Lincoff and D. H. Mitchel, Toxic and Hallucinogenic Mushroom Poisoning (Van Nostrand Reinhold, 1977), p. 30.]...

Poisoning and sometimes death from eating (unidentified) mushrooms is well known. In particular, Amanita sp. are particularly dangerous, with much emphasis on the death cap fungus , Amanita phalloides.24 The best known toxins are the amatoxins and phallotoxins, which are complex, bicyclic peptides. An unusual feature relates to sulfur a tryptophan (or substituted tryptophan) unit is linked to a cysteine sulfur at the carbon atom next to the NH group of the pyrrole ring, forming the unit, -CH2-S-C(NH)=C, e.g. in... 

Delayed-onset mushroom poisoning, usually caused by Amanita phalloides, A virosa, Galerina autumnalis, or G marginata, manifests its first symptoms 6-12 hours after ingestion. Although the initial symptoms usually include nausea and vomiting, the major toxicity involves hepatic and renal cellular injury by amatoxins that inhibit RNA polymerase. Atropine is of no value in this form of mushroom poisoning (see Chapter 58). 

Other species of amanita are among the deadliest fungi known. Polypeptide-like toxins in Amanita phalloides, or death cup, can prove fatal or at the very least can cause permanent liver and kidney damage. These mushrooms are common in the temperate climates of Europe and North America. They are responsible for the majority of what is called "slow" mushroom poisoning in the U.S. In fact, it was only a few years ago that the local newspaper reported a case of amanita poisoning within SLO county. Mushroom poisoning is known as mycetism. In addition the amanita also contain bufotenine which has CNS effects. See the ASIDE which discusses the peptide poisons. 

Pattern of serum alanine aminotransferase (ALT) and bilirubin in the plasma, following poisoning with the toxic mushroom Amanita phalloides. 

The poisonous components of the most deadly mushroom Amanita phalloides (the Death Cap) are bicyclic heptapeptides which have an additional covalent bond that connects the ( -sulfur atom of an l-cysteine residue with the carbon atom in position 2 of the indole ring of the L-tryptophan. Phalloidin (or phalloidine) is the most abundant member of a whole family of related cyclic heptapeptides called phallotoxins (for a review, see Wieland1 1). These poisonous peptides, therefore, contain a cross-linking moiety consisting of L-tryptophan coupled to L-cysteine, designated tryptathionine (1), alternatively called 5-(trypto-phan-2-yl)cysteine or 2-(L-3-alanylsulfenyl)-L-tryptophan (Scheme 1). 

The most useful inhibitor of eukaryotic transcription has been a-amanitin, a major toxic substance in the poisonous mushroom Amanita phalloides. The toxin preferentially binds to and inhibits RNA polymerase II (see table 28.4). At high concentrations it also can inhibit RNA polymerase III but not RNA polymerase I or bacterial, mitochondrial, or chloroplast RNA polymerases. 

Mushrooms are spore-forming bodies of filamentous terrestrial fungi, some of which are considered to be food delicacies, whereas others, such as Amanita phalloides, Amanita virosa, and Gyromita esculenta, are very toxic, with reported worldwide deaths of the order of 100 per year.10 In extreme cases, one bite of one poisonous mushroom can be fatal. Accidental mushroom poisonings are often caused by the death s head mushroom, because it is easily mistaken for edible varieties. 

Amanita phalloides, an extremely poisonous mushroom, popularly known as "Death Cap. ... 

Family in.— Agaricaceae, the gill family, in which the hymenium covers blade-like plates of the pileus, called gills, generally occurring on the under surface of the same. Examples Agaricus campestris, the common edible mushroom of fields Amanita muscaria and Amanita phalloides, both of which are poisonous. 

Cytochalasins, drugs that inhibit cellular processes that require actin polymerization and depolymerization (e.g., phagocytosis, cytokinesis, clot retraction, etc.), also act by severing and capping actin filaments. Actin filaments can be stabilized by phalloidin, derived from the poisonous mushroom Amanita phalloides. Assembly of actin filaments into bundles (as in microvilli) and three-dimensional networks is accomplished by two groups of cross-linking proteins (Table 21-6). 

Fig. 1 Pattern of LFTs following Amanita phalloides (a highly poisonous species of mushroom) toxicity.

Aqueous fractions from P. major leaves were found to be biologically active. They activate the complement system and induced the production of tumor necrosis factor alpha (TNF-a) by human moncytes in vitro [196]. Aucubin (19) reported to have liver protective effect and it was shown to be antidote for fatal mushroom poisoning caused by Amanita phalloides. It exhibited low toxicity [197]. In India, the leaves and roots of P. major are used for their astringent properties and to bring down fever. The seeds are taken as a cure for dysentery and are considered to have stimulant effects. 

Amanda Tin picked mushrooms in a wooded area near her home. A few hours after eating one small mnshroom, she experienced mild nausea and diarrhea. She brought a mushroom with her to the hospital emergency room. A poison expert identified it as Amanita phalloides (the death cap ). These mnshrooms contain the toxin a-amanitin. 

Muscarine from the mushroom. Amanita muse aria, has become a valuable biochemical tool for measuring peripheral effects on cholinergic receptors (see Volume 23 of this series). Each year Phalloidin from the mushroom. Amanita phalloides, causes several deaths in Europe from mushroom poisoning and has been the subject of a book by Theodor Wieland. In this volume, the subjects of alkaloids and mushrooms are brought together in a paper written by a team of experts from Poland in Alkaloids from Mushrooms. ... 

There are more than 5000 varieties of mushrooms in the United States, about 100 of which are potentially toxic. The majority of toxic mushrooms cause mild to moderate self-limited gastroenteritis. A few species may cause severe or even fatal reactions. The major categories of poisonous mushrooms are described in Table 11-38. Amanita phalloides and other amatoxin-containing mushrooms are discussed on p 273. 

The extremely poisonous green mushroom Amanita phalloides contains a number of cyclic peptides classified as phallotoxins (heptapeptides), ama-toxins (octapeptides), and a decapeptide antagonist called antamanide (Wieland and Wieland, 1972). Crystal structure analyses have been completed on jS-amanitin, on antamanide, and on a biologically active analog, both com-plexed and uncomplexed. 

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