Oxidative bioactivation of S-alkyl phosphorothiolate pesticides: stereospecificity of profenofos insecticide activation.
The mouse liver microsomal mixed-function oxidase system converts several phosphorothiolate pesticides with S-ethyl, S-propyl, or S-butyl groups to more potent inhibitors of acetylcholinesterase. This activation is stereospecific for the chiral isomers of O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothiolate (profenofos insecticide); the more toxic (-) isomer becomes a 34-fold better inhibitor of acetylcholinesterase in vitro, whereas the less toxic (+) isomer is deactivated by a factor of 2. Prior treatment of the microsomes with piperonyl butoxide or another mixed-function oxidase inhibitor markedly decreases the activation. Piperonyl butoxide also protects against brain acetylcholinesterase inhibition and cholinergic symptoms in chicks resulting from (-)-profenofos administration, thus establishing the importance of the oxidative bioactivation of S-alkyl phosphorothiolate pesticides in vivo.
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007306:Insecticides / Q000378:metabolism*; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D063086:Organothiophosphates / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000378:metabolism*; D010084:Oxidation-Reduction; D010882:Piperonyl Butoxide / Q000494:pharmacology; D013237:Stereoisomerism
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C024273:profenofos; D006899:Mixed Function Oxygenases; D010882:Piperonyl Butoxide