Chambers_1990_Pestic.Biochem.Physiol_36_308

The ability of rat liver aliesterases to noncatalytically detoxify the oxons of six phosphorothionate insecticides was studied; the insecticides were methyl parathion, parathion, chlorpyrifos-methyl, chlorpyrifos, leptophos, and EPN. All oxons were more potent inhibitors (nM range) of rat liver aliesterases than the target rat brain acetylcholinesterase, with the exception of methyl paraoxon. Rat liver homogenates (including EDTA to eliminate possible A-esterase contributions) increased apparent I50s of the oxons to bovine brain acetylcholinesterase, indicating a detoxication of an appreciable amount of the oxon. Except for EPN-oxon, detoxication ability correlated with aliesterase sensitivity to inhibition. Liver homogenates from rats treated in vivo with the phosphorothionates had a reduced detoxication capability which correlated highly with residual aliesterase activity. With the exception of methyl parathion, animals treated for 90 min with high doses of the phosphorothionates displayed higher liver aliesterase inhibition than brain acetylcholinesterase inhibition. Thus, liver aliesterases represent a significant alternative phosphorylation site for organophosphates, and their efficacy for detoxication is a function of relative affinities of the oxon for the aliesterases and acetylcholinesterase.