PRINCIPLES OF TOXICOLOGY - Biology East Borneo

17.7 ANIMAL VENOMS AND TOXINS 423of natural inflammatory substances. While investigating the toxicity of the Portuguese man-o’warjellyfish he discovered anaphylaxis, an acute life-threatening immune inflammatory response. Somevenoms can trigger large inflammatory responses of similar magnitude without an immune component.Other natural compounds, because of their allergenic nature, cause a delayed hypersensitivity responsecalled 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 theUnited States and Canada where these plants abound in cities as well as in rural environments. Contactwith these plants causes exudation of a mixture of similar compounds called urushiols, which are4-alkyl-substituted dihydroxyphenyl compounds (catechols). These substances are seldom inflammatoryduring the first exposure, but subsequently trigger a delayed immune response. The mechanisminvolves initial oxidation to the quinone, which then reacts with skin proteins and becomes animmunogen. 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 thymuslymphocytes then migrate to the skin and participate in the inflammatory response to subsequentexposures to the urushiol compounds. It is interesting that the lacquer used to provide a glossy surfacefor Japanese pottery is made from a plant related to poison ivy, which also contains urushiols. As thelacquered surface is allowed to dry in the heat, the urushiols are inactivated. Workers cannot entirelyavoid exposure to the urushiols in the fluid they initially apply. Fortunately, many become hyposensitizedor resistant after chronic exposure.17.7 ANIMAL VENOMS AND TOXINSReptiles and AmphibiansSnake venoms are complex mixtures of active components, which make their scientific investigationand 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 ofmost “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 (familyCrotalidae) and vipers (Viperidae) will be considered first. Then, we shall examine the cobra(Elapidae) and sea snake (Hydrophiidae) venoms, which also share common biochemical andpharmacological properties.The pit vipers (Figure 17.6) possess a heat-sensitive sensory organ within a pit next to each eyethat is used to sense the presence of warm-blooded prey; rattlesnakes, water mocassins, and copperheadsbelong to this group. Many pit vipers occur in North and South America, whereas vipers occuronly in Africa and Europe. In general (and there are some exceptions), pit viper and viper venoms havegreater local effects on the tissues where the bite occurs and on the cardiovascular system. Localizedtissue 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 pathologicalrelease of intracellular calcium stores in skeletal muscle, which may produce muscle necrosis.Hyaluronidase and collagenase enzymes break down the connective tissue elements, promoting thespread of the venom from the original site of the bite. Motor paralysis rarely occurs in the absence ofcardiovascular crisis, with one notable exception. The venom of the Brazilian rattlesnake, Crotalusdurissus terrificus, possesses a potent neurotoxin called crotoxin, which paralyzes peripheral nerveterminals, causing loss of neuromuscular transmission and flaccid paralysis.Since crotalid venoms for the most part contain similar toxins and enzymes, and species identificationis often impossible, most immunotherapeutic treatments of pit viper bites utilize a polyvalenthorse antivenin originally prepared with an antigenic mixture of several crotalid venoms. This approachhas been quite successful.