Amanita phalloides poisoning: Mechanisms of toxicity and treatment

Abstract

Amanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially α-amanitin, are the main responsible for the toxic effects in humans. It is recognized that α-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms.

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

“…These results show that the therapeutic effect of these drugs does not seem to be directly related to the binding with RNAP II but to other mechanisms. Therefore, an antidote that regenerates the RNAP II or that prevents the α-amanitin binding to RNAP II does not yet exist and clinical efficacy of the treatments after A. phalloides is still low (Garcia et al 2015a).…”

Mushrooms Intoxications

“…Amatoxins -alpha-, beta-and gammaamanitin are resistant to high temperatures, and alphaamanitin has the highest toxicity [1,10,13,14]. Intestinal mucosa, hepatocytes and proximal tubules of the kidney are the main target structures which are damaged by toxins of Amanita phalloides mushrooms [4,15,16,17]. Amatoxins directly interact with the enzyme RNA polymerase II in eukaryotic cells, inhibit transcription, prevent protein synthesis and cause cell death [15,18].…”

“…It continues from 6 to 40 hours [15,18]. The average duration of the latency period in our study was 11 hours [7][8][9][10][11][12][13][14][15][16][17][18][19][20] about 12-24 hours; c) Apparent convalescence -starts 36-48 hours after ingestion of mushrooms. Gastrointestinal symptoms diminish or disappear, but serum transaminases continued to increase, and jaundice may appear; d) Acute liver failure -characterized by high levels of transaminases, hyperbilirubinemia, coagulopathy, hepatic encephalopathy, hepatorenal syndrome and acute renal failure.…”

Death by food

“…A classic example of this is poisoning with the mushroom Amanita phalloides or "death cap" which has become more prevalent in recent times with the interest in "foraging" leading to the consumption of edible wild mushrooms [22,23]. Amatoxins in the mushrooms cause a sudden onset of nausea, vomiting and bloody diarrhea that is followed by progressive liver and kidney failure, coma and death [24]. Casper reported that there may have been complaints of "a disagreeable harsh taste in the throat" with "a feeling of disgust" [25].…”