Biological poisons

The term toxin is reserved for any toxicant of biological origin. Toxin fall into several broad categories based on the organism that produce them.

BacteriaFungi: MycotoxinsAlgae: PhycotoxinsPlant: PhytotoxinsAnimal: Zootoxins

BACTERIAL TOXIN

Botulinum ToxinNeurotoxin proteins (Anaerobic condition)Clostridium botulinum. (A-G)The most acutely substance, with lethal dose 200-

300 pg/kg (100 grams could kill most of human on earth)

BotulismToxin is composed of 2 polypeptide chains that

are connected by a disulfide bond: Light chain 50-kD Heavy chain 100-kD

Light chain of the toxinProtease enzyme (attack on Fusion protein) at

neuromuscular junction, preventing neurotransmitter vesicles from anchoring to the membrane.

Inhibit acetylcholine release

Interferes with nerve impulses.

Produce paralysis of muscles.

Heavy chain of toxin

Is important for targeting the toxin to specific types of axon terminals.

Attaches the toxin to proteins on the surface of axon terminals so that it can be taken into neurons by endocytosis.

Flaccid paralysisTreatment: Antitoxin antibodies

BOTOX/DYSPORT

Tetanus toxin

Casual agent: Clostridium tetani.Greek (tetanos: Stretched, rigid).Neuromuscular toxin.Tetnospasmin or Spasmogenic toxin.“Lockjaw”

TETNOSPASMIN

Heavy chain 100-KdLight chain 50-kD

Interferewith protein vesicles

Block the release ofCNS inhibitory

neurotransmitter(GABA)

CNS tetanic spasmsof skeletal muscle

Endotoxins

Endotoxin is not secreted in soluble form by bacteria as are exotoxins but rather in chemical components in the cell wall of bacteria that is released when the bacteria lyses (e.g. LPS)

Fever.Inflammation.

Lowering of blood pressure.

Septic shock

Physiologic Action of Lipopolysaccharide (LPS)

FUNGAL TOXIN

Poison MushroomsMushroom toxins

AmantinCoprineGyromitrinMuscrineOrellanineIbotenic acid

Primary toxicity associated with the Mushroom

Gastrointestinal Nausea, Vomiting, Abdominal Cramping.Disulfiram like effects No symptoms unless alcohol is consumed

with in 2-3 days.Neurotoxic Coma, Convulsion, Excitement, Depression.Cytotoxic Destruction of cells, especially liver and

kideny

MYCOTOXINSAflatoxins (Produced by molds)

Peanuts,corn,wheat,rice,dairy productsASPERGILLUS.Tropical & subtropical (Temperature, humidity high).Acute cases (Liver damage).Chronic cases associated with liver cancer.108 people died from eating contaminated grains (India).Killed 100,000 turkeys that were eating moldy peanuts.Aflatoxins B1 is most potent HEPATOCARCINOGEN.

Ergolines

Contamination of rye by Calviceps purpurea (Ergot fungus)

Convulsive Symptoms (e.g., Painful seizures and spasms, diarrhea, Itching, headaches, nausea and vomiting)

Central Nervous System Symptoms (e.g., hysteria, mania or psychosis).

Gangrenous symptoms (e.g., dry gangrene due to vasoconstriction of distal structures, fingers and toes; weak peripheral pulse; loss of peripheral sensation; edema; ultimately death and loss of affected tissues).

ANIMAL TOXINS

SPIDER VENOMWidow spider (lactrodectus spp).NeurotoxicLatrodectism (Pain first at localized at lymph

nodes,Nausea,hypertension,transiet tachycardia, bradycardia,profuse sweating, oliguria, cramps)

Inject venom into skin (0.1mm) 0.002mg

Brown recluse. Cytotoxic Hemolytic 0.48mg/kg LD50

Brazilian wandering.

0.00061-0.00157mg/kg

SCORPIONS2,000 SpeciesNeurotoxinDeath stalker (L.

quinquestriatus)

SCORPIONS

Androctonus Parabuthus Tityus

Hymenopterans

InsectsLocal tissue injurySystemic toxicityAnaphylactic response

LD50

Honey bee (2.8mg/kg)Velvet ant (71mg/kg)Paper wasp (2.4mg/kg)Yellow jacket (3.5mg/kg)Fire ants

(0.66mg/kg)

Box Jellyfish60 tentacles5,000 nematocystsTreatment: vinegar, ice pack

MollusksBlue ringed octopus.Painlessly kill a human with in 5 min.Inject neuromuscular venommaculotoxin and tetrodotoxin.Cone snails.Conus geographus (cigarette snail)

OCTOPUS

ShellfishAmnesic shellfish poisoning.Diarrheic shellfish poisoning.Neurotoxin shellfish poisoning.Paralytic shellfish poisoning.

Amphibians

Poison dart or “poison arrow”100 toxins identified in the skin secretions of

poison dart frogs (Dendrobates & Phyllobates).Phyllobates produce neurotoxin, batrachotoxin.LD50 . 50µgSome toads produce epinephrine,

norepinephrine.

Phyllobates

Dendrobates

Reptiles

3,500 species of snakes worldwide.Venomous snakes fall into six families:ElapidaeHydrophiidaeLaticaudidaeViperidaeColubridaeCrotalidae

Elapidae (cobras, kraits, mambas, coral snakes)

Hydrophiidae (sea snakes)

Laticaudidae (sea kraits)

Viperidae (old world vipers & adders)

Colubridae (bloomslang&keelblack)

Crotalidae(rattlesnakes,water moccasins,copperheads,bushmaster)

Snake venom

Poison is inhaled/ingested, venom is injected.

Hemotoxic heart and cardiovascular system.

Cytotoxic local damage.Neurotoxic brain and nervous system.Viperidae is hemotoxic and cytotoxic.Hydrophiidae and laticaudidae neurotxic.Snake venom complex mixture.

Snake venom

Protein,peptide,inorganic cations,metals,Lipid,carbohydrates,amines,AA.Enzymes.The typical venom consist of 25 different

enzymes.The most damaging is proteolytic enzyme

(proteases,peptidases,proteinases,hydrolases).

Antivenin

First was described more than 100y ago.Horses, sheep exposed to graduated doses of

venom until become hyper immunizedImmunoglobulin.Animal derived antivenin have potential for

hypersensitivity and anaphylaxis.A cocktail of antivenins can be used against

broad range of venoms.

Antivenin

Venom extractor