The presentation outline

 Definition of mushroom poisoning

 Mushroom poisoning: a proposed new clinical classification

 Mushroom Toxins: Chemistry and Toxicology

Within the phyla of kingdom of fungi, those that are of clinical interest,
Basidomycota and Ascomycota, present themselves at the end stage of their
development as spore-bearing full-bodied fruits referred to as mushrooms

Govorushkoa et al.,2019
 Mushrooms are the fruiting bodies of fungi and constitute a significant
food source.

 Many species of wild or field mushrooms are considered delicacies in

some cultures/countries. However, there are numerous mushrooms that
may prove toxic if eaten and distinguishing between “edible” and
poisonous species is often difficult.

 In addition, some “edible” species can prove toxic to some humans in

certain circumstances which may not be predictable.

 Poisoning as a consequence of ingesting mushrooms remains a health

problem. in many countries resulting in both morbidity and mortality.
The annual global fatality rate from eating mushrooms is unknown, but
speculatively may be at least 100 deaths/year, and is probably an
underestimate because of the approximate 50-100 deaths/year in Europe
alone.
 The authors reviewed the literature on mushroom poisoning,
concentrating on the period since the current major classification
published in 1994, to identify all new syndromes of poisoning and
organized them into a new integrated classification, supported by a
new diagnostic algorithm.

 New syndromes were eligible for inclusion if there was sufficient

detail about both causation and clinical descriptions.

 Criteria included: identity of mushrooms, clinical profile,

epidemiology, and the distinctive features of poisoning in
comparison with previously documented syndromes.

 Based on the result, the authors propose 6 major groups based on

key clinical features relevant in distinguishing between poisoning
syndromes.
Past classifications of mushroom poisonings such as the work of Spoerke and
Rumack 1994 :
Based on the result, the authors classified these into 6 broad groups and this
scheme represents the proposed new classification of mushroom poisoning,
based on the clinical presentation, not on the type of toxin

Group Classification Cause

1 Cytotoxic mushroom Organ pathology, causing either primary
poisoning hepatotoxicity, or primary ephrotoxicity.
2 Neurotoxic Neurotoxicity
mushroom poisoning
3 Myotoxic mushroom Rhabdomyolysis
poisoning
4 Metabolic, endocrine A wide variety of poisoning syndromes and
and related toxicity clinical presentations
mushroom poisoning
5 Gastrointestinal nausea, vomiting, diarrhoea, abdominal
irritant mushroom pain/cramps and, in severe cases
poisoning
6 Miscellaneous which do not fit within the previous 5 groups
adverse reactions to
mushrooms
Mushroom Toxins: Chemistry and Toxicology

 In essence, all of these groups (6 groups) share poisoning syndromes that are
related, as these mushrooms contain exceptionally powerful toxins.
 Thus, consumption of wild mushrooms may expose people to toxic or lethal
doses of poisons.
 Investigations into the chemistry and toxicology of toxic principles from
poisonous mushrooms began in the early 19th century, but extraordinary
progress has been made since the 1950s.
 At present, >100 mushroom toxins have been characterized, but many toxic
compounds have not yet been identified in several mushroom species such as
Amanita neoovoidea.
 Most mushroom toxins beyond their structures
1. Toxins from the Genus Amanita

 It has been estimated that there are 900−1000

species of Amanita in the world, and half of
them have been described. Some of the most
toxic known mushrooms found worldwide, as
well as some well-regarded edible species.

 Among them, Amanita phalloides (A. phalloides; death cap) is the most
dangerous poisonous mushroom species currently known.

 Cause 95% of all deaths from mushroom poisoning.

 Cholera-like symptoms of nausea, vomiting, and diarrhea begin 10−20 h after

ingestion, followed by damage to liver and kidney, and eventually death.

 Amatoxins are absorbed by the intestinal tract and target the liver, and
hepatocellular effects represent the most lethal and least treatable
manifestations.
Predicted Biosynthesis
Process of Toxic Peptide
in Amanitaa

Structures of toxic amino acids (24,

25) and isoxazoies (26−28) from
genus Amanita.

L-2 amino-4-pentynoic acid (and L-

2-amino-4,5- hexadienoic acid.
Injection of 24 into mice induced
liver cell necrosis andreduced the
activity of hepatic enzymes,
2. Toxins from the Genus Cortinarius

The first reported poisoning related to the mushroom

Cortinarius orellanus (C. orellanus) was in 1957 and
involved 102 people, 11 of whom died.

 Orellanine has toxic effects in humans as well as in cats, mice, and guinea pigs
and causes histopathological changes in the kidneys, liver, and spleen, and
identical effects can be caused by consumption of intact fruiting bodies or their
methanolic extracts.
 orellanine can be oxidized to the o-semiquinone radical, orellinine (30) both
enzymatically by a tyrosinase/ O2 system and photochemically using visible
light. During this chemical process, a large number of superoxide radicals are
produced, which cause damage to DNA, RNA, and proteins
3. Toxins from the Genus Psilocybe

Magic mushrooms, such as Psilocybe mexicana (P.

mexicana), have a long history of religious use by the
indigenous cultures of Mesoamerica and South
America

 Psilocybin has no effect on isolated organs, as it is dephosphorylated in the

body and converted into the active metabolite psilocin.
 Psilocin exerts psychoactive effects by altering neurotransmission through
serotonin (5-HT) receptors 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2C but binds to
 5-HT2A receptors with high affinity.
 In contrast, psilocybin has potential clinical applications in treating anxiety
disorders, obsessive compulsive disorder, major depression, and cluster
headaches
4. Toxins from the Genus Clitocybe

 Clitocybe acromelalga (Cl. acromelalga), a Japanese poisonous mushroom,

is nonfatal but causes strong allodynia and burning pain that is marked by
reddish edema (erythromelalgia).

 These compounds are isolated from Cl. acromelalga. ACROs are responsible
for the poisonous aspects of the mushroom due to their potent
neuroexcitatory and neurotoxic properties.
5. Toxins from the Genus Gyromitra

The false morel, Gyromitra esculenta (G. esculenta), is a widely consumed and
delicious mushroom (eaten dried or boiled in northern European countries), even
though it has been suspected in a number of severe poisoning cases. The
symptomatology of this poisoning can include simple gastroenterological
disorders, hepatic and neurological seizures, and death
 Gyromitrin (LD50 20−50 mg/kg) is a slightly volatile and heat-sensitive liquid,
easily decomposing to the more toxic Nmethyl-N-formlhydrazin (MFH),
followed by N-methylhydrazine (monomethylhydrazine, MH, LD50 4.8−8
mg/kg) high temperature or under specific physiological conditions.
 The liver toxicity of gyromitrin is mainly caused by MFH, which is then
converted by the liver MFO system into a nitrosamide.
Mechanism for
Toxicology of
Gyromitrin in Vivo
6. Toxins from the Genus Coprinopsis.

 Coprinopsis atramentaria (Cp. atramentaria) is

another interesting poisonous mushroom, as this
species is nontoxic in the absence of alcohol but
induces toxic reactions when combined with
ethanol
 When consumed with alcohol, the mushroom retards the rate of ethanol
metabolism and induces elevated levels of acetaldehyde in the blood,
provoking an “antabuse effect,”
 This suggests that coprine is not a direct inhibitor of aldehyde dehydrogenase,
but the active agent is probably a coprine metabolite. The active in vivo
metabolites have been identified as cyclopropanone hemiaminal (53) and
cyclopropanone hydrate (54), both of which inhibit aldehyde dehydrogenases,
while the latter is more stable than the former
 Cyclopropanone hydrate irreversibly binds to and blocks the aldehyde
dehydrogenase active site, inhibiting enzyme activity and resulting in a
significant increase in systemic acetaldehyde concentrations.
 Thus, the toxic symptoms of coprine, flushing of the face and arms, throbbing
headache, cardiovascular arrhythmia, low blood pressure, tachycardia,
paresthesia of the extremities, and anxiety are actually due to an abnormal
increase in acetaldehyde concentration
7. Toxins from the Genera Omphalotus.

 Omphalotus illudens (O. illudens) is commonly called the jack-o’-lantern

mushroom and causes vomiting, cramping, and diarrhea when ingested.

 Illudins S (55) and M (56) (Figure 8) were isolated from the fruiting bodies
and are believed to be the main toxins.
 The closely related moonlight mushroom, O. japonicas (redirected from
Lampteromyces japonicas (L. japonicas)), which grows in Japan and other
Asian countries, is a poisonous and bioluminescent mushroom, also
causing vomiting, stomachache, and diarrhea.
 The structures of illudins S and M are suggestive of alkylating activity.
 In vivo, thiols (e.g., methylthioglycolate, cysteine, and glutathione) react
readily with the illudins, adding to the α,β-unsaturated carbonyl.
 The cyclohexadiene intermediate rapidly opens the cyclopropane and loses the
tertiary hydroxyl and the α,β-unsaturated ketone moiety plays an important
role in toxicity..
 Therefore, the antitumor activity of the illudins might be due to spontaneous
reaction with enzymes containing thiol groups, e.g., glyceraldehyde 3-
phosphate dehydrogenase or ribonucleotide diphosphate reductase, to inhibit
DNA synthesis or act directly as alkylating agents of DNA.
 This suggests that this toxin could act as an anticancer drug.
8. Toxins from the Genus Gymnopilus.

The genus Gymnopilus contains a large variety of hallucinogenic mushrooms,

and psilocybin was detected in 14 Gymnopilus species in America and Europe.

 Gymnopilins activate the neuronal

system of rats, indicating that
gymnopilins activate phospholipase
C and mobilize Ca2+ from
intracellular Ca2+ storage in non-
neuronal cells from the DRG.
 ymnopilins may be distributed into
the central nervous system by
crossing the blood−brain barrier and
could act directly on cells in the
central nervous system to excite the
vasomotor center.
9. Toxins from the Genus Hypholoma.
Hypholoma fasciculare (H. fasciculare) is a bitter and poisonous mushroom
that contains characteristic lanostane triterpenoids: fasciculols.
Among these triterpenoids, fasciculols E and F are toxic agents
10. Toxins from the Genus Hebeloma

The poisonous mushroom Hebeloma vinosophyllum

(He. vinosophyllum) causes neurotoxic and
gastrointestinal toxicity.

Poisonous mushroom belong to Hebeloma is He. Spoliatum (Japanese name,

ashinaganumeri), and its toxic compounds are HS-A, HS-B, and HS-C (90−92)
Conclusion

 Mushroom consumption is a global tradition that is still gaining popularity.

However, foraging for wild mushrooms and accidental ingestion of toxic
mushrooms can result in serious illness and even death.

 The proposed new classification of mushroom poisoning is the result of the

considered efforts to create an organized strategy to assist patient care
Decisions.

 The information on the chemistry including chemical structures is have

different toxicology.
 References

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Poisoning associated with the use of mushrooms: A review of the global pattern
and main characteristics. Food and Chemical Toxicology 128. (2019) : 267–279.

Julian White, Scott A. Weinstein, Luc De Haro, Regis Bédry, Andreas Schaper, Barry
H. Rumack, Thomas Zilker, Mushroom poisoning: a proposed new clinical
Classification, Toxicon (2018), doi: 10.1016/j.toxicon.2018.11.007.

Xia Yin, An-An Yang, and Jin-Ming Gao. Mushroom Toxins: Chemistry and
Toxicology. J. Agric. Food Chem. (2019)67, 5053−5071.