Poisonous Plants, Fungi, and Algae I - Poisonous and Toxic Fungi

Fungal Toxins Mushroom Toxins Mycotoxins

Mushroom Toxin Groups I - Amanitins (Cyclopeptides) II - Gyromitrin (Monomethylhydrazine) III – Orellanine IV - Coprine V - Muscarine VI - Ibotenic acid and Muscimol - already discussed VII - Psilocybin (psilocin) - already discussed VIII - Gastrointestinal irritants

Mushroom Structure

Cellular Toxins I - Amanitins - Cyclopeptides II - Gyromitrin - Monomethylhydrazine III -Orellanine

Group I: Distrubution of Amanitins Amanita bisporigera, A. phalloides, A. verna, A. virosa Galerina autumnalis, G. marginata, etc Lepiota spp. Conocybe filaris

Destroying Angels A. virosa and A. verna

Amanita phalloides

Galerina autumnalis

Conocybe filaris

Phallotoxins (Phalloidins) Cyclopeptides (amino acids in a ring) Phallotoxins consist of 7 amino acids in a ring Cause cell destruction in liver? Attack plasma membrane - bind to protein receptors Cells leak Ca++ and then K+ Toxin enters cytoplasm and attacks organelles by rupturing lysosome membrane Evidence suggests these may not be lethal because it does not appear to be absorbed through the intestine in experimental animal studies

Amatoxins (Amanitins) 8 amino acids in a ring Also cause cellular destruction Attacks cells with high rates of mitosis First attacks GI tract, produces lesions in stomach which cause initial symptoms - vomiting, severe diarrhea, pain Toxin is then absorbed into blood and carried to liver where most of the damage occurs

Amatoxins in the Liver Toxin invades nucleus of liver cells Destroys nucleolus and inhibits mRNA polymerase Toxin circulates to kidneys and attack kidney cells then re-enter blood stream and back to liver Amatoxins are LETHAL

General Structure of Amatoxin

Symptoms of Amatoxin Poisoning Within 5 to 24 hours - diarrhea, vomiting, and pain (typically 6 to 12 hours) Short remission and apparent improvement 4 to 11 days later severe liver damage acute kidney failure coma and death

Treatment of Amatoxin Poisoning No antidote Supportive care - pump stomach, restore fluid balance Activated charcoal to absorb toxins in stomach Plasmapheresis Liver transplant Other treatments which may inhibit toxin uptake by hepatocytes High dose penicillin G - one million units/kg on 1st day and 500,000 units for next two days Silibinin - water soluble extract of milk thistle

Group II - Gyromitrin (Monomethylhydrazine) Gyromitra brunnea, G. caroliniana, G. esculenta, G. fastigata, G. infula, G. gigas Helvella elastica, H. lacunosa Paxina spp. Sarcosphaera crassa

Morel False Morel Morchella Gyromitra

Gyromitrin Poisoning Gyromitrin hydrolyzes to monomethylhydrazin (rocket fuel) which is highly toxic Resembles Amanita poisoning but is less severe. Latent period of 6 - 10 hours after ingestion Followed by sudden onset of abdominal discomfort (feeling of fullness), severe headache, vomiting, and sometimes diarrhea, pain, cramps The toxin primarily affects the liver with additional disturbances to blood cells and the central nervous system - may result in loss of coordination, coma, convulsions

Group III - Orellanine Distribution - Cortinarius orellanus, C. orellanoides, C. reainierensis Long latent period of 3 to 14 days - attacking kidneys Burning thirst, excessive urination - first symptoms Followed by nausea, headache, muscular pains, chills, spasms, and loss of consciousness In severe cases, kidney failure may result in death Fatty degeneration of the liver and severe inflammatory changes in the intestine accompany the renal damage

Toxins Affecting Autonomic Nervous System IV - Coprine V - Muscarine

Group IV - Coprine Distribution Coprinus atramentarius - inky cap Possibly other Coprinus species Coprinus micaceus Coprinus fuscescens Coprinus insignis Coprinus spp. (some African species) Clitocybe clavipes

Coprine Coprine interfers with breakdown of alcohol Chemically this compound is very similar to Antabuse Symptoms occur usually within 5 to 30 minutes after eating this mushroom, if alcohol has been ingested within the past 72 hours

Coprine Poisoning Hot and sweaty face, becoming flushed Flushing spreading to the neck and chest Rapid, difficult breathing, Rapid heart rate Violent headache Nausea and vomiting Lasts for 2 - 3 hours

Group V - Muscarine Inocybe species Clitocybe species Amanita muscaria and Amanita pantherina were previously thought to have contained primarily muscarine - but they contain insignificant amounts

Muscarine Poisoning Characterized by increased salivation, perspiration, and lacrimation within 15 to 30 minutes after ingestion With large doses, symptoms may be followed by abdominal pain, severe nausea, diarrhea, blurred vision, and labored breathing Intoxication generally subsides within 2 hours Deaths are rare, but may result from cardiac or respiratory failure in severe cases Atropine is the antidote (only one with antidote)

Toxins Affecting the Central Nervous System VI - Ibotenic Acid and Muscimol VII - Psilocybin and Psilocin

Group VIII - Gastrointestinal Irritants Large variety of mushrooms contain toxins that can cause gastrointestinal distress, including but not limited to nausea, vomiting, diarrhea, and abdominal cramps Symptoms similar to those caused by the deadly protoplasmic poisons - but usually have a rapid onset Some mushrooms may cause vomiting and/or diarrhea which lasts for several days

Chlorophyllum molybdites

Chlorophyllum molybdites

Mycotoxins

Mycotoxins Background Health effects Carcinogenic Immediate toxic effects Immunosupression History – Turkey X Disease – Aspergillus flavus

Aflatoxins Aflatoxin: A (aspergillus) - fla (flavus) - toxin Four toxins soon identified: aflatoxin B1, B2, G1, G2 - (B and G refer to blue or green florescence under uv-light) Today known to be 10 aflatoxins Aflatoxin B1 most important - highly carcinogenic and widespread occurrence in foods

Sources of aflatoxins Produced by 3 species of Aspergillus: A. flavus, A. parasiticus, A. nomius Aspergillus flavus a common fungus that occurs on grains and legumes A. parasiticus most toxigenic species Aflatoxins not only toxic but also carcinogenic, mutagenic, and teratogenic

Aflatoxin B1 is Mutagenic Hepatocellular carcinoma (HCC) is a major cause of mortality in certain areas of the world About 50% of the HCC cases in parts of the world where food is contaminated with AFB1show a mutation in codon 249 of p53 tumor suppressor gene Mutation consists of transversion of G->T in the third position of codon resulting in serine instead of arginine - lab studies confirm

Aflatoxin levels Permissible limits generally quite low (15-20 parts per billion in US - lower in Europe) for human food Some scientists feel that no detectable levels of aflatoxins should be permitted because of the carcinogenic effects

Other mycotoxins Today over 400 mycotoxins have been identified from 150 species of fungi with new ones discovered each year Ergot alkaloids now considered mycotoxins Species of Aspergillus, Penicillium, Fusarium, Alternaria, Cladosporium and Stachybotrys form mycotoxins

Common toxigenic fungi Aspergillus Penicillium Common toxigenic fungi Stachybotrys Fusarium

Ochratoxins Produced by species of Aspergillus such as Aspergillus ochraceus Most important is Penicillium verrucosum which occurs on grains Ochratoxin A a nephrotoxin responsible for nephropathy in pigs and probably humans It is immunosuppressive and also assumed to be carcinogenic in humans - in animal studies it is one of the strongest carcinogens

Patulin Produced by a number of species of Penicillium, Aspergillus and Byssochlamys. Most important producer is Penicillium expansum. Fungus causes a soft rot of apples; toxin found in apple juice Patulin first attracted attention as an antibiotic in 1943; no current interest in antibiotic properties because it is too toxic

Trichothecenes Produced by several species of Fusarium One of the most toxic is T-2 Believed T-2 responsible for outbreak of alimentary toxic aleukia (ATA) in Siberia during and after World War II In some areas 10% of the population developed the disease and in most cases it was fatal

Alimentary Toxic Aleukia - ATA Characterized by nausea, vomiting, hemorrhages in many organs, bleeding from nose and throat, bloody diarrhea, low leukocyte count, exhaustion of bone marrow About a third of deaths due to strangulation from internal swelling of throat Years later scientists made the connection between the disease and consumption of moldy grain Symptoms appeared when people ate 2 kg of moldy grain, 6 kg was lethal. Similar hemorrhagic syndrome in animals called moldy corn toxicosis

Vomitoxin (Deoxynivalenol) A trichothecene produced by some Fusarium spp. Produces vomiting in pigs at low concentrations Much less toxic than T-2 but immunosuppressive Contaminates corn, barley, and wheat Permissible limits are 0.3 ppm for flour and 0.1 ppm in bread or breakfast cereal During recent wet growing season, Ontario farmers lost $17 million on a wheat harvest contaminated with vomitoxin.

Macrocyclic trichothecenes More toxic than T-2 Produced by Stachybotrys chartarum (S. atra) and also by species of Myrothecium Specific toxins are satratoxins, verrucarins, and roridins Responsible for the deaths of many horses, but it can also affect cattle, pigs, sheep, poultry Complex of unpleasant symptoms like ATA. Stachybotrys found indoors in many locations growing on ceiling tiles and wallboard Concern about airborne inhalation of spores

Yellow rain During the Vietnam war, there was concern that the Viet Cong were using chemical weapons against the US as well as the population in Laos and Cambodia Victims were sprayed with a yellow rain Symptoms were like ATA (possibly some evidence of trichothecene toxins in some of the victims. However, the issue was not clear cut) Little evidence Viet Cong using chemical weapons Samples of the yellow rain deposits later shown to be largely made up of pollen - “cleansing flight theory” This issue has never been resolved

Exposure in Contaminated Environments In contaminated indoor environments, people may be inhaling hundreds to thousands of fungal spores per hour If the spore are toxigenic, risks may occur Many different types of fungi occur indoors Most common genus is Cladosporium - just like it is outdoors Penicillium and Aspergillus often exist at higher concentrations indoors Stachybotrys has received most media attention over the past 9 years

Stachybotrys Soil fungus in nature Commonly found indoors on wet materials containing cellulose, such as wallboard, jute, wicker, straw baskets, and paper materials Spores in slimy mass Thought to be allergenic although little is known May produce potent mycotoxins

Stachybotrys

Health effects from airborne exposure? Clinical studies not completed yet Possible correlations in contaminated buildings but no experimental studies with human exposure Animal studies suggest effects of respiratory exposure may be important but may not correlate with exposure levels Possible effects: immune suppression, rash, headache, fatigue, sore throat, pulmonary hemorrhage (in infants) We need more research