PRINCIPLES OF TOXICOLOGY

of natural inflammatory substances. While investigating the toxicity of the Portuguese man-o’war
jellyfish he discovered anaphylaxis, an acute life-threatening immune inflammatory response. Some
venoms can trigger large inflammatory responses of similar magnitude without an immune component.
Other natural compounds, because of their allergenic nature, cause a delayed hypersensitivity response
called contact dermatitis. One of the best known cases is the response to poison ivy (Figure 17.5),
poison oak, or poison sumac. This is a major hazard to most inhabitants of certain countries like the
United States and Canada where these plants abound in cities as well as in rural environments. Contact
with these plants causes exudation of a mixture of similar compounds called urushiols, which are
4-alkyl-substituted dihydroxyphenyl compounds (catechols). These substances are seldom inflammatory
during the first exposure, but subsequently trigger a delayed immune response. The mechanism
involves initial oxidation to the quinone, which then reacts with skin proteins and becomes an
immunogen. The stimulated Langerhans cells of the skin migrate to the thymus, where they, in turn,
stimulate the production of thymic lymphocytes capable of responding to urushiol. These thymus
lymphocytes then migrate to the skin and participate in the inflammatory response to subsequent
exposures to the urushiol compounds. It is interesting that the lacquer used to provide a glossy surface
for Japanese pottery is made from a plant related to poison ivy, which also contains urushiols. As the
lacquered surface is allowed to dry in the heat, the urushiols are inactivated. Workers cannot entirely
avoid exposure to the urushiols in the fluid they initially apply. Fortunately, many become hyposensitized
or resistant after chronic exposure.
17.7 ANIMAL VENOMS AND TOXINS
Reptiles and Amphibians
17.7 ANIMAL VENOMS AND TOXINS 423
Snake venoms are complex mixtures of active components, which make their scientific investigation
and envenomation treatment quite a challenge. The vast literature on the folklore, natural history,
scientific investigation, and medical treatment of poisonous snake bites has attracted the interest of
most “toxinologists.” Many presentations at meetings of the International Society of Toxinology
(announced in the Society journal, Toxicon) are on snake venoms.
There are four families of poisonous snakes. The similar venoms of the pit vipers (family
Crotalidae) and vipers (Viperidae) will be considered first. Then, we shall examine the cobra
(Elapidae) and sea snake (Hydrophiidae) venoms, which also share common biochemical and
pharmacological properties.
The pit vipers (Figure 17.6) possess a heat-sensitive sensory organ within a pit next to each eye
that is used to sense the presence of warm-blooded prey; rattlesnakes, water mocassins, and copperheads
belong to this group. Many pit vipers occur in North and South America, whereas vipers occur
only in Africa and Europe. In general (and there are some exceptions), pit viper and viper venoms have
greater local effects on the tissues where the bite occurs and on the cardiovascular system. Localized
tissue swelling (edema) results from protein hemorrhagic toxins, which attack the capillary endothelium,
making it leaky to blood cells as well as plasma proteins. Protein myotoxins cause a pathological
release of intracellular calcium stores in skeletal muscle, which may produce muscle necrosis.
Hyaluronidase and collagenase enzymes break down the connective tissue elements, promoting the
spread of the venom from the original site of the bite. Motor paralysis rarely occurs in the absence of
cardiovascular crisis, with one notable exception. The venom of the Brazilian rattlesnake, Crotalus
durissus terrificus, possesses a potent neurotoxin called crotoxin, which paralyzes peripheral nerve
terminals, causing loss of neuromuscular transmission and flaccid paralysis.
Since crotalid venoms for the most part contain similar toxins and enzymes, and species identification
is often impossible, most immunotherapeutic treatments of pit viper bites utilize a polyvalent
horse antivenin originally prepared with an antigenic mixture of several crotalid venoms. This approach
has been quite successful.