Toxic Effects of Terrestrial Animal Venoms and Poisons

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Toxic Effects of Terrestrial Animal Venoms and
Poisons

• Shawn Lipe
• ENVS 531
• November 2002

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Venomous

• Animals capable of producing a poison in highly
  developed secretory glands
• Deliver toxin in a biting or stinging act
• Capture and digestion of food
• Only designed to immobilize, not kill
• Contributes to animals defense

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Venom

• Offensive
• Oral pole
• -snakes
• -spiders
• -ants
• -centipedes

• Defensive
• aboral pole/ spines
• -stingrays
• -scorpions
• -bees

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Poisonous

• Animal whose tissues are either partially or
  entirely toxic
• Usually ingested- no delivery mechanism
• Widely distributed in animal kingdom
• Usually derive their toxins through the food
  chain, subject to bioconcentration

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Venoms

• May contain up to 100 high and low molecular
  weight proteins
• Amines, lipids, steroids, aminopolysaccharides,
  quinones, glucosides, free amino acids, and
  histamines

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Bioavailability of Venom

• Composition
• Molecular Size
• Concentration Gradient
• Solubility
• Ionization
• Rate of blood flow

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Absorption of Venom

• Specialized active or passive transport
• Facilitated diffusion
• Pinocytosis- invagination of venom into a vesicle
  that later releases inside the cell interior

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Receptor Sites

• variable degree of sensitivity
• variable degree of metabolism
• critical minimum concentration

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Metabolism

• Affected by protein binding, pH, and membrane
  permeability
• High affinity sites- neurotoxin, cardiotoxin, and
  myotoxin
• Enzymes located in parenchymal cells and unevenly
  through other tissues
• Excretion primarily through kidneys

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Arthropods

• Arachnids- scorpions, spiders, mites, ticks
• Myriapods- centipedes, millipedes
• Lepidoptera- butterflies, catapillars
• Hymenoptera- ants, bees, wasps
• Insects- assassin bugs, water bugs
• Beetles- blister beetles

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Diagnosis

• Countries do not keep records of insect related
  death
• Spider bites mimic other diseases
• Stings or bites may induce stress reactions that
  bring an unrecognized disease to the surface

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Scorpions

• 75 known venomous species worldwide
• Neurotoxic fraction classified by M(r)
• 30-40 a.a. affect K or Cl- channels
• 60-70 a.a. affect Na
• Impairs the initial depolarization of the action
  potential in the nerve and muscle

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Spiders

• Over 200 known venomous species
• Widow- neurotransmitter release and
  channel-affecting activity
• Orb spinners- Ca2 channel blocking
• Jumping spiders- glutamate and Ca2 channel
  blocking

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Latrodectus-Black Widow

• Alpha-latrotoxin, 1000 a.a.
• Effects the vertebrate central nervous system in
  depolarizing neurons by increasing Ca2
• Numbness, weakness, muscle pain, sweating,
  lymphadenitis, hypertension
• calcium gluconate, methocarbamol

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Loxosceles- Brown Spider

• Sphingomyelinase D
• Demonstrates a complement dependent hemolytic
  activity and a dermonecrotic inducing factor
• Coagulation, vasoconstriction, anemia
• Corticosteroids, skin grafting

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Ticks

• Tick paralysis caused by the saliva
• Respiration affected, acetylcholine reduced
• Functional deficiency in afferent fibers
• Paresis, paralysis
• Removal produces immediate recovery

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Snakes

• 400 known venomous species
• Cobras, mambas, kraits, coral and sea snakes,
  vipers, adders, rettlesnakes, moccasins,
  bushmasters, copperheads
• There are no poisonous snakes in New Zealand,
  Hawaii, and Ireland

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Snake Venom

• 90-95 protein by dry weight
• _at_ 25 catalytic enzymes
• Cations Na, Ca2, K, Mg2
• Metals Zn, Fe, Co, Mn, and Ni
• Trace carbohydrates, lipids, biogenic amines

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Proteolytic Enzymes

• Catalyze the breakdown of tissue proteins and
  peptides
• a.k.a. protease, hydrolase, peptidase
• Several in a single venom
• Some inactivated by edetic acid (EDTA)
• Metals involved in protease activation

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Thrombin-like Enzymes

• Defibrinatig anticoagulant
• Glycoproteins- M(r) 29,000-35,000
• Clinically prevents thrombosis formation
• Used as defibrogenating agents in stroke, angina,
  renal transplant rejection, myocardial
  infarction, and pulmonary embolus

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Hyaluronidase

• Catalyzes the cleavage of internal glycoside
  bonds in acid polysaccharides
• Decreased connective tissue viscosity
• Increased venom penetration
• spreading factor

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Other Enzymes

• Acetylcholinesterase
• RNase
• DNase
• NAD nucleotidase
• L-Amino acid oxidase
• Lactate dehydrogenase

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Polypeptides

• Crotoxin- neurotoxin
• 50 of the total protein
• Presynaptic interference with acetylcholine
  release
• Desensitization of the acetylcholine receptor
• Circulatory failure

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Toxicology

• blood vessel integrity
• Blood coagulation mechanisms
• Cardiac and pulmonary dynamics
• Nervous system
• respiration

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Shock or Hypotension

• Decrease in circulating blood volume
• Increase in capillary permeability
• Loss of fluid, protein
• Dose related

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Antivenom- IgG

• Venom specific antisera concentrated from immune
  serum to the venom
• Contain neutralizing antibodies
• Bind to venom molecules
• 50 h half-life
• Large molecular size, high VOD
• Degraded in reticuloendothelial system

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Questions

• Explain the difference between poisonous and
  venomous?
• What qualities account for the extreme toxicity
  of snake venom?