SOURCES

There are two species of venomous lizards in the world. Both species belong to the genus Heloderma and are found in the Americas. Two Heloderma (gila monster) species, H. suspectum and H. cinctum, are found in the United States in an area extending from southern Utah through most of Arizona, areas of New Mexico and Nevada, and a small part of California. They are also found in Sonora, Mexico, west to the Gulf of California. The other species of Heloderma, H. horridum (the Mexican beaded lizard), is significantly larger than other Helodermatids and occupies parts of Mexico and Guatemala.¹

These lizards are heavy bodied, large (adult gila monsters can reach 55 cm in length), and generally slow moving, but can strike relatively quickly. Their tails are blunt and rounded and may measure one-half of the lizard’s total body length. They have tough, bead-like skin scales, which on gila monsters form a dark reticular pattern on a yellowish-orange background. The head is held low, has a rounded muzzle, and is flat and large. They have heavy mandibular musculature and a short neck. The feet are hand-like and clawed.

The venom from these lizards is used for defense only because these animals raid burrows and nests, consuming eggs and preying on the young of birds and small mammals. The venom is excreted from venom glands located on the lower jaw. The venom delivery apparatus is poorly developed and relies on the grasping and chewing action of the lizard.² The venom apparatus consists of bilateral venom glands connected by a venom duct to the gums at the base of the teeth in the lower jaw. The venom is pulled up along grooves in these teeth by capillary and chewing action. Gila monsters bite tenaciously, and victims may be presented for veterinary care with the lizard still firmly attached.

TOXIC DOSE

The low end of the toxic dose for humans has been estimated at 8 mg venom (dry weight).³ The average gila monster has a venom yield of 15 to 20 mg of venom (dry weight). The intravenous (IV) median lethal dose (LD₅₀) of venom in mice is 0.5 to 1 mg/kg of body weight. As a point of reference, the IV LD₅₀ of western diamondback rattlesnake venom in mice is 2.18 mg/kg of body weight. The toxic dose for dogs and cats is unknown. Because of the poor venom delivery system of the lizard, the degree of envenomation is most likely a function of the duration of the bite. The author is aware of at least one fatal bite in a 20-kg dog. The dog was found agonal with the lizard still firmly attached; the duration of the bite was unknown.

TOXICOKINETICS

The toxicokinetics have not been extensively studied.

MECHANISM OF TOXICITY

In animal studies, IV administration of Helodermatid venom into dogs and cats induced an initial tachypnea followed by a decrease in rate and depth of respiration, and eventual respiratory collapse. Increases in both lacrimation and salivation were noted, coupled with vomiting and polyuria. No confirmed evidence of coagulopathy has been identified, although there still is some suspicion that this may occur. Tachycardia, cardiac irregularities, and marked hypotension have also been described.⁴

Heloderma venom contains multiple fractions, which include hyaluronidase, arginine hydrolase, kallikrein-like enzymes, and phospholipase. Additionally, several other proteins have been identified. These include a pancreatic secretory protein exhibiting phospholipase activity, gilatoxin, helothermine, and a toxin that inhibits a contraction response to direct stimulation of isolated mouse diaphragm.⁵

Hyaluronidase, called the “spreading factor,” facilitates the uptake of the venom by decreasing the viscosity of connective tissue through catalyzing the cleavage of internal glycoside bonds of some acid mucoglycosides. Destruction of the hyaluronic acid barrier permits the other venom components to penetrate deeper into the victim’s tissue.⁶

Arginine hydrolase directs its activity toward hydrolysis of the peptide linkage to which an arginine residue contributes to a carboxyl group. The exact impact of this venom component has not been well defined, but it may have a bradykinin releasing—like effect.⁵

Kallikrein-like enzymes mimic the action of kallikrein by causing vasodilatation, increased capillary permeability, edema, and contraction or relaxation of extravascular smooth muscles. These enzymes also attract leukocytes and induce pain when injected subcutaneously.

Phospholipase has been identified in many types of venom and exists as a variety of isoenzymes. One action of phospholipase is to uncouple oxidative phosphorylation, thereby inhibiting cellular respiration. Phospholipase can also contribute to the release of other active enzymes by causing membrane destruction along with other compounds like histamine, kinin, serotonin, acetylcholine, and slow-reacting substance.

Gilatoxin is an acidic neurotoxic protein.⁷ Helothermine depresses the body temperature in mice that have been injected with this toxin.⁸