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The role of carboxylesterase in species variation of oxime protection against soman

1991; Elsevier BV; Volume: 15; Issue: 1 Linguagem: Inglês

10.1016/s0149-7634(05)80105-8

1873-7528

Donald M. Maxwell, Karen M. Brecht,

Insect-Plant Interactions and Control

Oxime protection against soman, a highly toxic anticholinesterase agent, was examined in mice and guinea pigs. The maximal protection produced by the oximes PAM and HI-6 varied as much as 6-fold between these species. Since endogenous carboxylesterase (CaE) is known to be an important determinant of species variation in soman toxicity, the protection of PAM and HI-6 against soman was also measured in animals whose endogenous CaE was inhibited with cresylbenzodioxaphosphorin oxide. In CaE-inhibited animals the soman LD50 values were similar in unprotected mice and guinea pigs (10.2 vs. 12.2 μg/kg) and oxime-protected mice and guinea pigs (38.1 vs. 40.3 μg/kg for PAM; 159 vs. 151 μg/kg for HI-6). The levels of oxime protection observed in CaE-inhibited animals agreed with previous experiments in other species that have no endogenous plasma CaE. The 4–5 times greater in vivo protection against soman of HI-6 vs. PAM in CaE-inhibited animals correlated with in vitro experiments in which HI-6 produced 3–5 times more oxime reactivation of soman-inhibited AChE than PAM.