Animal Toxins • Venomous Animal is capable of producing a poison in a highly developed gland or group of cells and can deliver the toxin by biting or stinging • Poisonous Animal contains tissues that are, in whole or part, toxic and there is no mechanism to deliver the poison. Properties of Animal Toxins • Composition & Chemical properties – Proteins, peptides, enzymes, amines, lipids, steroids, amino polysaccharides, etc. • Toxic Effects? • Variables affecting the action of Venoms – Route of administration – Absorption – Distribution – Passage across membranes – Accumulation – Metabolism & excretion Antivenoms (Antivenins) • Elicit immune responses-proteins • Antiserum development – IgG or fragments such as Fab or F(ab)2 – Removal of Fc or complement binding part • Complications of Antisera - anaphylaxis 1 Reptiles • Venomous Species of Snakes – Elapidae – Hdrophiidae – Laticudidae – Viperidae – Crotalidae – Colubridae • Venomous Lizards – Gila Monster & Mexican beaded lizard Snake Venoms • Proteins & peptides • Inorganic ions – Na+, Ca2+, K+, & Mn2+ – Trace amounts of Zn, Fe, Co, Mg, & Ni • Other components – Carbohydrates (glycoproteins) – Lipids – Biogenic amines – Free amino acids Enzymes of Snake Venoms • Proteolytic enzymes • Phosphomonoesterase • Arginine ester hydrolase • Phosphodiesterase • Thrombinlike enzyme • Acetylcholinesterase • Collagenase •RNase • Hyaluronidase • DNase • Phospholipase A2(A) • 5’-Nuclease • Phospholipase B • NAD-nucleotidase • Phospholipase C • L-Amino acid oxidase • Lactate Dehydrogenase 2 Toxicology of Crotalids • Direct tissue damage & necrosis • Alterations in Blood vessel resistance • Changes in RBCs and blood coagulation • Indirect effects on cardiac and pulmonary dynamics • Alterations of NS function • Changes in metabolism & respiration • Hypotension - shock Amphibian Toxins • Toad Toxins – Chemical composition • Biogenic amines – epinephrine, nor epinephrine, dopamine, epinine, indolealkylamines –Actions • Vasoconstriction, hypotension, hallucinations • Smooth muscle • Frog Toxins – Chemical composition – Bicyclic & Steroid alkaloids – Phyllobatis sp. – dart poisons – Atelopus sp. • Zetekitoxins AB & C – LD = 11µg/kg & 80 µg/kg • Tetrodotoxin & Batrachotoxin – LD mouse = 100ng; LD human = 200 ng Venomous Arthropods • Arachnids - Spiders – Widow Spiders – Latrodectus • Venom – Neurotoxic proteins (5-6) high content of isoleucine and leucine & low content of tyrosine – Proteolytic enzymes & hyaluronidase • Toxicity – Muscle pain, cramps, fasciculation – Joint pain – Headache & dizziness –edema 3 Venomous Arthropods • Spiders (cont.) – Brown or Violin Spiders – Loxosceles sp. •Brown recluse • Venom – Sphingomyelinase D Phospholipase – Protease Esterase – Collagenase Hyaluronidase – DNase & RNase Derma necrosis 33 & 37 •Toxicity – Vascular damage & tissue necrosis – Lethality – intravascular hemolysis, thrombocytopenia, hemoglobinuria, renal failure Venomous Arthropods • Hymenoptera – Ants, Bees, Wasps, Hornets – Lethality due to sensitization to the venom & anaphylactic reactions – Venom • Peptides & nonenzymatic proteins • Phospholipase A & B • Hyaluronidase • Histamine & 5-hydroxytryptamine. Plant Toxins • Variable responses to plant toxins – Concentration of chemicals in different parts – Age of plant – Climate & soil – Genetic differences 4 Toxic Effects in the GI System • Effects – irritation causing nausea, vomiting, diarrhea • Agents – Lectins & Alkaloids – Castor bean – lectins, ricin I & ricin II – Autumn crocus bulbs – colchicine – Vinca - vincristin Toxic Effects on Skin • Effects – physical & chemical irritation, hypersensitivity reactions • Agents – alkaloids, Ca-oxalate crystals, resorcinols • Toxin producing plants – Philodendron & Toxicodendron – Resorcinols • 5-n-heptadecatrienyl resorcinol – Bulb plants – narcisus, daffodils, tulips,& dieffenbachia • Ca-oxalate crystals • Trypsin-like inflammatory protein – histamine & serotonin release Cardiovascular System Toxicity • Effects – nausea, emesis, hypotension, hypertension, vasoconstriction, bradycardia • Agents – Vasoactive & cardioactive alkaloids • European yew, Monkshood, Ergot – Cardiac glycosides • Foxglove, Oleander, Misletoe 5 Nervous System Toxicity • Effects – neuromuscular blocking, neurotoxicity, excitation, • Agents – Neuromuscular blocking • Curare - Strychnos & Chondrodendron • Anatoxin A – Anabaena flos-aquae • Methylcaconitine - Larkspur – Excitatory Amino Acids • Kainic acid – red algae-Digenea simplex • Ibotenic acid – Amanita muscaria • Scopolamine & Atropine – Jimsonweed, Foxglove Liver toxicity • Toxin classes – Pyrrolizidine alkaloids, cyclic & bicyclic heptapeptides, sphingosine-like compounds • Pyrrolizidine alkaloids (ragweed, crotalaria (rattlebox), heliotrope, comfry) – Hepatic damage resembling cirrhosis & tumors • Phalloiden & Amatoxin – Amanita Phalloides – Cyclic & bicyclic peptides – Strong affinity for liver RNA polymerase II 6.