Guinea pigs nerve agent toxicity

Pyridostigmine bromide studies have been performed in dogs, guinea pigs, monkeys, rabbits, rats, and mice. Diarrhea, salivation, tremors, and respiratory failure were seen prior to death. Side effects of the drug are related to muscarinic and nicotinic effects. Toxicity is also related to cholinergic stimulation. Effectiveness of pretreatment to reduce lethality after exposure to nerve agents (in particular, soman) is dependent on the administration of atropine and pralidoxime, postexposure. 

FIGURE 10.6 Posttreatment with galantamine/atropine effectively counteracts nerve agent and insecticide toxicity in guinea pigs. Lower the level of OP exposure, longer the time within which the antidotal therapy effectively maintains 100% survival of the animals with no signs of toxicity. (From Albuquerque, E.X. et al., Proc. Natl. Acad. Set USA, 103, 13220, 2006. With permission.)... 

These studies firmly establish that prophylactically administered ChE, with no additional therapy, prevents the toxicity induced by highly toxic OP nerve agents in mice, rats, guinea pigs, and rhesus monkeys. Not only do these bioscavengers prevent lethality, but animals do not show any untoward side effects or performance decre-ments/deficits determined by the Morris Water Maze task, SPR task, PEP task, or spatial discrimination task. 

Table 6 shows the toxicities of the four classical nerve agents in guinea pigs together with estimates of human toxicity by the inhalation route. Estimates of human toxicity data have been extrapolated from animal data. Toxicity in rodents is ranked in the order guinea pig > rat > mouse. The guinea pig is the best rodent model for primates. 

TABLE 6. Acute toxicities of nerve agents in guinea pig and man (estimated)... 

Fig. 6. Summarization of results correlating inhibition efficacy (piso) and toxicity (log LD50) for some OP and nerve agents. Equation y = 9.87 — 1.26x p < 0.01 rxy = —0.9489. The lines indicate experimentally determined piso (human brain AChE) values (axe y) or extrapolated values (axe x) of LD50 for systox and VX. Each point represents the value of piso corresponding to LD50 value for rabbit, rat, guinea pig, mouse, and dog. The compounds under code are designated by the abbreviation of the oxyalkyl group on the phosphorus head, and by the alkyl on the nitrogen atom - e.g. VX is designated as Et-iPr (modified from B11, B14 and P3).

Wang, Y, Oguntayo, S., Wei, Y.L., et al., 2012. Neuroprotective effects of imida-zenil against chemical warfare nerve agents soman toxicity in guinea pigs. NeuroToxicol. 33, 169-177. 

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