Poisonous Plants, Fungi, and Algae

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

2. Fungal Toxins • Mushroom Toxins • Mycotoxins

3. 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

4. Mushroom Structure

5. Cellular Toxins • I - Amanitins - Cyclopeptides • II - Gyromitrin - Monomethylhydrazine • III -Orellanine

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

7. Destroying Angels A. virosa and A. verna

8. Amanita phalloides

9. Galerina autumnalis

10. Conocybe filaris

11. 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

12. 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

13. 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

14. General Structure of Amatoxin

15. 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

16. 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

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

18. Morel False MorelMorchellaGyromitra

19. 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

20. Group III - Orellanine • Distribution - Cortinariusorellanus, 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

21. Toxins Affecting Autonomic Nervous System • IV - Coprine • V - Muscarine

22. 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

23. 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

24. 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

25. 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

26. 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)

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

28. 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

29. Chlorophyllum molybdites

30. Chlorophyllum molybdites

31. Mycotoxins

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

33. 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

34. 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

35. 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

36. 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

37. 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

38. Aspergillus Common toxigenic fungi Penicillium Stachybotrys Fusarium

39. Ochratoxins • Produced by species of Aspergillus such as Aspergillusochraceus • 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

40. Patulin • Produced by a number of species of Penicillium, Aspergillus and Byssochlamys. • Most important producer is Penicilliumexpansum. • 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

41. 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

42. 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

43. 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.

44. 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

45. 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

46. 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

47. 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

48. Stachybotrys