Effect of Endogenous Carboxylesterase on HI-6 Protection against Soman Toxicity

摘要

Species variation in oxime protection against soman was examined in mice andguinea pigs with the bis-pyridinium oxime HI-6. HI-6, an effective reactivator of soman-inhibited acetylcholinesterase, produced greater maximal protection against soman in mice than in guinea pigs, although there was no species difference in acetylcholinesterase reactivation. In mice the maximal therapeutic dose of HI-6 increased the LD 50 of soman from 113 micro grams/kg in unprotected animals to 992 micro grams/kg in animals receiving 76.6 mg/kg of HI-6 and 11.2 mg/kg of atropine. In guinea pigs the maximal therapeutic dose of HI-6 increased the LD50 of soman from 28.2 micro grams/kg in unprotected animals to 179 micro grams/kg in animals receiving 136 mg/kg of HI-6 and 16mg/kg of atropine. In animals whose carboxylesterase had been inhibited with 2 mg/kg of cresylbenzodioxaphosphorin oxide, the soman LD50 values in unprotected mice and guinea pigs were similar (10.2 vs. 12.2 micrograms/kg), as were the soman LD50 values in mice and guinea pigs protected with HI-6 and atropine (159 vs. 151 micrograms/kg). In cresylbenzodioxaphosphorin oxide-treated mice and guinea pigs the achievement of equal HI-6 to produce equal levels of reactivation of soamn-inhibited acetylcholinesterease in both species). (js)