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 MorelMorchella Gyromitra
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 - 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

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-gtT 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
Common toxigenic fungi
Aspergillus
Penicillium
Stachybotrys
Fusarium
39
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

40
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

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
49
(No Transcript)
50
(No Transcript)
51
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