Factors modifying the toxicity of organophosphorous compounds including soman and sarin

Abstract

I N T R O D U C T I O N The primary target for the organophosphorous insecticides and nerve agents, such as Satin and Soman, is the enzyme acetylcholinesterase (ACHE). The inhibit ion of AChE is followed by an increase in the level of ACh, in the brain up to about 100% (Fonnum and Guttormsen, 1969). The symptoms accompanying poisoning by the organophosphorous compounds: increased secretion, gastrointestinal disturbance, miosis, tremors and at last death through anoxia may be explained by a larg~ excess of ACh at the cholinergic receptors and thereby an ove:rstimulation of the cholinergic system. The cause of death is anoxia due to a combination of factors such as central respiratory paralysis, severe bronchoconstriction and weakness or paralysis of the accessory muscles of respirat ion(Sire, 1975). : In the simple and well acknowledged scheme there are several factors which are often neglected, but which may be important in discussing therapy or prophylaxis against organophosphorous poisoning. In this paper we wi l l discuss the possible contribution of enzymes other than AChE to the toxicity of the organophosphorous compounds. In particular we wish to focus the attention to aliesterases, a group of esterases, which are inhibited by Satin and Soman to almost the same extent as ACHE. These enzymes could act almost as scavengers by reacting i r revers ib lywi th the organophosph0rous compounds and thereby removing them before they react wi th the ACHE. There are also other enzymes wi th a high aff inity for organophosphorous compounds and which inactivate these compounds by hydrolysis. In the present paper we wi l l demonstrate the efficiency of the latter in a perfused liver preparation.