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Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Mushroom poisoning or mycetism is connected with widely varying classes of neurotoxins.364 These include Amanita muscaria, which produces ibotenic acid, muscimol and muscazone, and Inocybes and Clitocybes mushrooms, which produce muscarine. Amanita phalloides is the most toxic mushroom; they synthesize amatoxins: cyclic octapeptides and phallotoxins:cyclic heptapeptides.90,165,268 The principal amatoxin is amanitin, and the most important phallotoxin is phalloidin. The action of various mushroom toxins resides in the effects on several nerve functions such as GABA-like action inhibiting central neurons, inhibition of RNA polymease II, depletion of nuclear RNA preventing protein synthesis, and disruption or dissolution of cell membranes and membranes of lysosomes, endoplasmic reticulum, and Golgi bodies.176,231,268
Amatoxin
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Despite their overwhelming health benefits, mushrooms have a dark side of the story that should not be overlooked. That is, out of about 10,000 mushroom species, 50–100 are known to produce various toxins (including deadly amatoxin, orellanine, monomethylhydrazine, and ergotamine; potentially deadly muscarine and ibotenic acid; and nonlethal phallotoxin, coprine, arabitol, bolesatine, muscimol, psilocybin, and psilocin). Inadvertent ingestion of toxin-producing mushrooms by humans and animals can lead to gastrointestinal, neurological, and other discomforts as well as deaths [1].
Fungi and Water
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
The genus Amanita belonging to the family Amanitaceae has many toxic species including Amanita phalloides (death caps), A. pantherina (panther cap), A. citrina (false death cap), A. muscaria (fly agaric), A. ibotengutake (Japanese ringed-bulb amanita), A. smithiana (North American Lepidella), A. proxima (Mediterranean Amidella), A. virosa, A. verna, A. bisporigera, A. ocreata, A. suballiacea, A. tenuifolia and A. hygroscopica (94–96). The species Amanita phalloides (death caps) may be the deadliest of all mushrooms in the world, and is responsible for the majority of fatalities caused by mushroom poisoning (96). The toxins involved belong to the amatoxin and phallotoxin complexes (95–97). Amatoxins are bicyclic octapeptides and powerful thermostable poisons. The most potent amatoxin is α-amanitine, and is among the nine amatoxins that have been recognized (97). Ataxia, motor depression, euphoria, dizziness, gastrointestinal disturbances, drowsiness, muscle twitches, and changes in insight, feelings, and mood are common symptoms associated with amatoxin poisoning (97). Phallotoxin includes phalloin, phalloidin, phallisin, phallacidin, phallacin, and phallisacin (96). Phallotoxin causes alterations of enterocytes cellular membrane, while amatoxin inhibits protein synthesis at a transcriptional level within enterocytes, hepatocytes, and proximal renal tubular cells. After ingestion of A. phalloides (death caps), these toxins tend to accumulate in the liver, damaging it severely (95). Amatoxin causes necrosis of liver cells with mortality rates ranging from about 10% to 20%. Only a minority of patients need liver transplantation (96). Poisoning by A. phalloides (death caps) is a medical emergency requiring immediate hospitalization.
Lepiota cristata does not contain amatoxins or phallotoxins
Published in Toxin Reviews, 2018
Ismail Yilmaz, Ilgaz Akata, Sinan Bakirci, Ertugrul Kaya
The toxicity of lethal mushrooms relates to two different toxins: amatoxins and phallotoxins. While phallotoxins have limited poisons, amatoxins are the agents mainly responsible for clinical poisoning. Hence, in clinical practice often amatoxins are of interest for toxicologically study (Kaya et al., 2013; Yilmaz et al., 2014,2015). Analysis methods, such as thin-layer chromatography (TLC), radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), capillary zone electrophoresis (CZE) (Abuknesha & Maragkou, 1993; Brüggemann et al., 1996; Faulstich et al., 1982; Gérault & Girre, 1975) utilized in the determination of amatoxin and phallotoxin levels in fatal mushrooms and biological fluids have given their places to more delicate and susceptible advanced methods including high-performance liquid chromatography (HPLC), liquid chromatography–high-resolution-mass spectrometry (LC–HR-MS), LC electrospray ionization (ESI) time-of-flight (TOF) - (MS), matrix-assisted laser desorption ionization (MALDI)-TOF MS (Ahmed el al., 2010; Gicquel et al., 2014; Gonmori et al., 2012; Kaya et al., 2013; Yilmaz et al., 2014).
How can monoclonal antibodies be harnessed against neglected tropical diseases and other infectious diseases?
Published in Expert Opinion on Drug Discovery, 2019
Mushroom poisonings occur across tropical, subtropical, and temperate climates, but share some similar characteristics with animal envenomings and neglected tropical diseases and have thus been included in this review. About 5000 different species of mushrooms exist, with about 50 species being poisonous to humans [15]. In contrast to venom toxins that due to their size and proteinaceous nature are unable to be absorbed in the gastrointestinal tract, mushroom poisons comprise small oligopeptidic toxins that can be readily absorbed in the gastrointestinal tract and are thus toxic when ingested [91]. Most of the mushroom species involved in lethal poisonings are found in the genus Amanita, which produces amatoxins, phallotoxins, and virotoxins [99]. Of these toxins, the amatoxins are of highest medical concern, and they retain their potent hepatotoxicity even upon boiling. Their mode of action involves inhibition of the RNA polymerase II, responsible for transcription of mRNA [100]. Even today, the treatment options for mushroom poisonings caused by amatoxins remain inadequate, and severe cases of poisoning can necessitate liver transplantation [101–105]. Despite their small size, amatoxins may invoke an immune response, and researchers have reported the development of both IgG and Fab-based monoclonal antibodies using hybridoma technology [106]. Interestingly, when these two different antibody formats were assessed for their ability to neutralize amatoxins in a murine model, it was discovered that instead of neutralizing the toxins, both antibody types enhanced toxicity. Particularly, the Fab antibody was shown to dramatically enhance toxicity 50-fold, as the Fab antibody increased the accumulation of the toxin in the kidneys, causing major nephrotoxicity [106]. More than a decade ago, it was reported that attempts to use antibody-based therapies against mushroom poisonings had not been successful [15], and this finding remains the status quo. It is thus uncertain whether effective antibody-based therapeutics may ever find their way into the field of mushroom poisoning; however, the possibility cannot be entirely excluded. Some of the many recently developed advanced antibody formats, such as bispecifics and novel binding protein scaffolds, may offer improved or entirely different mechanisms of action and pharmacokinetics that might find their utility in mushroom poisoning therapy.