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Chapter 4
Biological Poisons:
Plant and Animal Toxins
Biological Poisons
• Earth is home to an impressive array of toxic and
venomous organisms.
• Nature in general produces chemicals far more toxic
than anything a human can concoct.
• Many have been used for research purposes to study
physiological mechanisms, a number are used
clinically, and others have served as prototypes to
develop synthetic chemicals of medical importance.
Biological Poisons
• Toxins are poisonous substances produced by
living things, usually for the purpose of
defense or predation.
• They are effective in very small amounts.
Toxins
• The term toxin is reserved for any toxicant of
biological origin.
• Toxins fall into several broad categories based
on the organism that produces them:
– Bacteria
– Fungi: mycotoxins
– Algae: phycotoxins
– Plants: phytotoxins
– Animals: zootoxins
Toxins
• Venom is an animal toxin that is produced in a
poison gland or group of cells and is delivered
to another animal through a bite or sting.
• This is referred to as envenomation.
Botulinum Toxin
• Collection of neurotoxic proteins that are
produced under anaerobic conditions by the
bacterium Clostridium botulinum.
• Amount of toxin to produce a lethal effect is
approximately 0.0002 µg/kg body weight
• Likely the most acutely toxic substance known
• Clostridium spores are ubiquitously found in
soil globally
Botulinum Toxin
• Composed of two polypeptide chains that are
connected by a disulfide bond:
– 50-kDa light chain that produces muscle paralysis
– 100-kDa heavy chain is important for targeting the
toxin
• Is used in very small amounts both as a cosmetic
treatment and to treat painful muscle spasms (e.g.,
the esophagus) and is sold under the brand names,
respectively, Botox and Dysport.
Table 4-2 Comparison of the
Toxicity of Botulinum Toxin with
Several Other Chemical Substances
Did You Know?
• In small doses, BoNT, the causative agent of
botulism, has multiple clinical applications for
such disparate conditions as spasmodic
dysphonia, cervical dystonia, blepharospasm,
hyperhydosis, spasticity, migraine headaches,
and glabellar lines. This is an excellent
illustration of how a dose can determine if a
substance is poisonous.
Did You Know?
• BoNT is used in very small amounts both as a
cosmetic treatment and to treat painful
muscle spasms (e.g., the esophagus) and is
sold under the brand names Botox and
Dysport. The use of BoNT to treat muscle
hyperactivity disorders is based on its ability
to block motor neuron function. This is also
the basis of its cosmetic applications.
Did You Know?
• The effect of the toxin lasts an average of 3 to 4
months for all clinical applications. Reinjection is
then necessary. Botox is also used for some
conditions characterized by chronic pain. Pain
reduction has been shown to precede and outlast
muscle relaxation. It has also been shown to
affect uninjected muscle groups; therefore,
antinociceptive mechanisms may include
mechanisms other than muscle relaxation.
Tetanus Toxin
• Clostridium tetani is the causal agent.
• It is an anaerobic bacterium whose spores
germinate under very low oxygen levels.
• It is introduced into the body generally through
skin wounds such as lacerations, abrasions, and
occasionally from body piercing or tattooing.
• It is an extremely potent neuromuscular toxin
that is responsible for all the symptoms produced
in humans and other mammals.
Tetanus Toxin
• Is referred to as tetanospasmin or spasmogenic
toxin.
• Was described by Hippocrates 25 centuries ago
• Produces a hypercontracted state of the skeletal
muscle that is often fatal
• Death results from respiratory and heart failure
• Is composed of two polypeptide chains connected by
a disulfide bond:
– the heavy 100-kDa chain binds onto the cell
– the light 50-kDa chain interferes with the protein
vesicles that contain the neurotransmitters
Figure 4-1 Tetanus toxin movement from
peripheral to central nervous system
Endotoxins
• Are known to cause an inflammatory response
in the human respiratory tract.
• Are not secreted in soluble form by live
bacteria; they are a chemical component in
the cell wall released when the bacteria lyses.
Endotoxins
• The main endotoxin is the lipopolysaccharide
(LPS) complex associated with the outer
bacterial wall in most gram-negative bacteria.
– LPS is often used synonymously with
endotoxin and consists of a polysaccharide
chain and a lipid, often referred to as lipid A
– Lipid A produces the toxic effects of the
bacteria.
Endotoxins
• Are associated with:
– fever
– inflammation
– lowering of blood pressure
– If enough is present, the individual can go into
“septic shock”
– associated with the exacerbation of respiratory
conditions
Case in Point
In September 2011, a Warrenton woman and her friend
were treated at Georgetown University (GU) Hospital
for mushroom toxicity. Liver specialists treating the
women believe they consumed Amanita bisporiger, a
toxic mushroom alternately referred to as “Destroying
Angel” or “Avenging Angel.” Members of the Amantia
family are extremely hepatotoxic and there is no
federally approved course of treatment. Amantia
bisporiger is commonly found in the Midwest and
Pacific Northwest of the United States.
Case in Point
They are often mistaken for the paddy straw
mushrooms and the Volvariella speciosa. GU physicians
used an experimental drug known as silibinin, offered
through the research unit of the Georgetown
Transplant Unit. Silibinin is a flavolignan derived from
milk thistle and has been used experimentally as a
chemopreventative in colorectal, oral, prostate, and
lung cancers. There are two clinical endpoints for
Amantia poisoning, slow recovery or liver failure
requiring transplant.
Mushroom Toxins
• Cannot be made nontoxic by cooking, freezing, or
other forms of food processing
• Prognosis depends on the species and the amount of
consumption
• Four categories of toxic effect based on the primary
toxicity:
– Gastrointestinal Effects
– Disulfiram-Like Effects
– Neurotoxic Effects
– Cytotoxic Effects
Mushroom Poisoning
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•
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•
•
•
•
Amanitin (Amanita phalloides, Amanita virosa)
Coprine (Coprinus atramentarius)
Gyromitrin (Gyromitra esculenta, Gyromitra gigas)
Ibotenic acid (Amanita muscaria, Amanita pantherina)
Muscarine (Clitocybe dealbata, Inocybe geophylla)
Muscimol (Amanita muscaria, Amanita pantherina)
Orellanine (Cortinarius orellanus)
Psilocybin (Psilocybe cubensis, P. mexicana, Conocybe
cyanopus)
Mycotoxins
• Produced by molds that infest peanuts, corn, wheat,
rice, tree nuts, dairy products, and other agricultural
plants.
• Produced primarily by members of the genus
Aspergillus
• Grow well in tropical and subtropical areas
• Exposure can occur from the consumption of
contaminated food
• Chronic exposure to aflatoxin has been associated
with a specific form of liver cancer.
Trichothecenes
• Most important structural features are the
12,13-epoxy ring, the presence of hydroxyl or
acetyl groups at appropriate positions on the
trichothecene nucleus, and the structure and
position of the side chain
• They have been called radiomimetic toxins
because they affect rapidly reproducing cells
Trichothecenes
• Are represented by several toxins (e.g., T-2
toxin, diacetoxyscirpenol, deoxynivalenol)
• Are produced by species of Fusarium, a mold
that grows under cool to cold conditions on
grains, alfalfa, tomatoes, fruits, and other
substrates
• They are a group of sesquiterpenes produced
by various Fusarium species.
Ergolines
• Contamination of rye by Claviceps purpurea
(ergot fungus) produces several powerful
ergoline derivatives (e.g., methylergometrine,
ergotamine). Symptoms include:
– convulsive symptoms (e.g., painful seizures)
– central nervous system symptoms (e.g.,
psychosis)
– gangrenous symptoms (e.g., dry gangrene)
Ergolines
• Ergot has an interesting history and was first
mentioned in the early Middle Ages as the
cause of outbreaks of mass poisonings
affecting thousands of individuals.
• The illness appeared in two characteristic
forms: convulsive (ergotismus convulsivus)
and gangrenous (ergotismus gangraenosus).
Ergolines
• The gangrenous form of ergot has been
referred to as “St. Anthony’s Fire” because
victims in the Middle Ages, numbering in the
thousands, were treated by the monks of the
Order of St. Anthony.
• The chemicals in ergot have been used to
synthesize chemicals that may be of medicinal
importance, including LSD.
Algal Toxins
• The Cyanobacteria of the plant kingdom
Monera are known by the common name
blue-green algae.
• They are primitive photosynthetic organisms,
with about a dozen toxic species found on
land, in freshwater, and in the oceans
• Some marine blue-green algae are responsible
for a form of contact dermatitis known as
“swimmers itch”
Algal Toxins, cont.
• The species Microcystis produces cyclopeptide
hepatotoxins (nodularin and microcystin)- linked to
liver cancer
• Anabaena produces the neurotoxin saxitoxin and an
extremely neurotoxic alkaloid, anatoxin, also referred
to as the “very fast death factor.”
– The anatoxins affect the nervous system, often
causing death due to paralysis of the respiratory
muscles
– Saxitoxins are also neurotoxins; however, they
function in a fashion similar to tetrodotoxin
Algal Toxins: Divisions
• True algae are present fall within a number of
divisions:
– Division Chrysophyta: Diatoms are abundant,
economically important and represent an
important source of food in both freshwater and
marine environments.
– Division Euglenophyta: Euglenoids are flagellated
unicellular plants that make up part of the diet of
aquatic invertebrates.
Algal Toxins: Divisions cont.
– Division Chlorophyta: The green algae are
represented by numerous species abundant in
freshwater and represent an important part of the
aquatic food chain.
– Division Rhodophyta: The red algae include
seaweeds, which represent an important food
source and are a source of carbohydrates such as
carrageen and agar.
Algal Toxins: Divisions cont.
– Division Phaeophyta: The brown algae (or
seaweed) are often referred to as kelp and are an
important food source for marine organisms and
humans.
– Division Pyrrophyta: The dinoflagellates are
unicellular algae that are important sources of
food in freshwater and marine environments.
These algae are of toxicological importance
because they are associated with massive fish kills
and contamination of shellfish.
Dinoflagellates and Red Tides
• Red tide refers to the reddish orange-brown color of
coastal water during outbreaks of certain species of
dinoflagellates, particularly Karenia brevis
• Blooms occur almost every year off the west coast of
Florida and are associated with massive fish and bird
kills
• Toxins, collectively referred to as brevetoxins, are of
several types of neurotoxic lipid-soluble chemicals
Higher Plant Toxins
• Many higher plants produce harmful
substances that can produce injury and death
if ingested
• Toxins are present in fruit, vegetable, garden,
outdoor ornamental, and wild plants
Higher Plant Toxins
• Plant toxins can be classified based on their general
chemical structure:
– Alkaloids (e.g., Yew)
– Proteins and amino acids (e.g., Castor bean)
– Glycosides (e.g., Foxglove, Oleander)
– Oxalates (e.g., Dieffenbachia, Rhubarb)
– Phenols, resins, and volatile oils (e.g., Poison Ivy,
Poison Oak, Poison Sumac, Rhododendrons)
– Phototoxins (e.g., St. John’s Wort)
Did You Know?
• Yerba mate (Ilex paraguariensis) is used to
create a popular tea ingested worldwide. The
practice of drinking yerba mate infusion may
be associated with the ingestion of potentially
pathogenic fungi, in particular Aspergillus
species. Some of these fungi are able to
survive extreme variations in pH and
temperature. This is a potential problem for
immunocompromised individuals.
Spider Venoms
• Widow spiders (Lactrodectus spp.)
– venom is neurotoxic
– Latrodectism describes the effects (pain, nausea,
muscle contractions and cramps, etc.)
• Recluse spiders (Loxosceles spp.)
– venom is cytotoxic and hemolytic
– Loxoscelism describes the local and systemic
effects (particularly necrosis)
Table 4-3 Comparison of the
Toxicity of Three Species of Spiders
Animal Toxins, cont.
• Scorpions
– venom is generally neurotoxic
– interferes with neurotransmission
– most species are relatively harmless to
humans
Animal Toxins, cont.
• Hymenopterans
– envenomations can be painful and produce
local tissue injury
– venom from single stings is essentially
insufficient to produce systemic toxicity
unless the victim is allergic to the venom
Cnidarians
• Jellyfish, hydroids, corals, and anemones
– polyps or medusas
• Venom apparatus is the nematocyst
– capable of discharge upon chemical/mechanical
stimulation even if animal is dead
• Box Jellyfish has stings so excruciating that victims
are in danger of going into shock and drowning
before they can reach medical attention
• Portuguese Man-of-War is a colony of four distinct
types of polyps, each with a specialized function
Mollusks
• There are two species of blue-ringed octopus that
share the ability to painlessly kill a human within
5 minutes. There is no known antidote.
• The bivalve mollusks are associated with toxicities
related to their consumption. Poisonings are
usually classified as Amnesic, Diarrheic,
Neurotoxic, or Paralytic shellfish poisoning
• Some species of cone snails are responsible for
the recorded deaths of several dozen humans.
Peptides derived from venoms have shown
promise as pain killers.
Amphibians
• More than 100 toxins have been identified in
the skin secretions of poison dart frogs,
especially Dendrobates and Phyllobates.
• The toxin may be derived from the frog’s diet
• The practice of “frog licking” to get high has
resulted in some individuals being hospitalized
due to severe hallucinations.
Reptiles
• Venomous snakes fall into six families:
– Elapidae (cobras, kraits, mambas, and coral
snakes)
– Hydrophiidae (sea snakes)
– Laticaudidae (sea kraits)
– Viperidae (Old World vipers and adders)
– Colubridae (boomslang and keelback)
– Crotalidae (rattlesnakes, water moccasins,
copperheads, and bushmasters)
Table 4-5 Common Snake Venom
Enzymes and Their Effects