PECULIARITIES OF METABOLITES TOXICOKINETICS OF G-TYPE ORGANOPHOSPHORUS NERVE AGENTS IN BIO FLUIDS OF RATS SUBECTED TO ANTIDOTE THERAPY

Abstract

The effect of the Pelixim antidote on the possibility to detect markers of G type nerve agents sarin and soman was studies in bio probes obtained in an acute in vivo experiment after exposure of rats to organophosphorus nerve agents in doses of 0.5LD50. It was found out that the intake of equitoxic doses of soman and sarin leads to a decrease of acetylcholinesterase erythrocyte membrane (AChE) activity for up to 7 days after exposure. The effect of Pelixim on the recovery of erythrocyte AChE activity is mostly pronounced a day after sarin poisoning. The fluoride regeneration of nerve agents from blood plasma protein adducts was possible for up to 7 days after soman poisoning without antidotal therapy and for 3 days after with antidotal therapy; in case of sarin intoxication, fluoride regeneration was possible for 3 days regardless of the use of antidotal therapy . The antidote strongly affected the excretion of hydrolytic metabolite of sarin О-isopropyl methylphosphonic acid (IMPA) and had no effect on the excretion of hydrolytic metabolite of soman О-pinacolyl methylphosphonic acid (PMPA). A day after poisoning and Pelixim injection, IMPA was detected in urine at a level of 15.3 ng/ml, whereas its level in the urine samples of animals in the absence of antidotal therapy was 55.0 ng/ml; 3 days after poisoning, IMPA was detected at a level of 4.9 ng/ml exclusively in the urine of animals subjected to antidotal therapy. The urine levels of PMPA in animals subjected and not subjected to antidotal therapy were respectively 44 and 53 ng/ml a day after poisoning and 12 and 14 ng/ml respectively 3 days after poisoning. Thus, the antidote impact on the excretion profile of hydrolytic metabolites is more significant for sarin than that of soman.