Methyl parathion activation by a partially purified rat brain fraction.
Organophosphorus pesticides are one of the most commonly used insecticide classes. They act through a potent inhibition of acetylcholinesterase (AChE). Many of them must undergo transformation into the corresponding oxon analogs to inhibit AChE. This study showed that a brain tissue subfraction transformed methyl parathion (O,O-dimethyl O-p-nitrophenyl phosphorothioate) in vitro. Methyl parathion activation was assayed by solvent extraction of the products followed by HPLC and GC-MS analyses and, indirectly, by the inhibition of AChE present in the incubation mixture. The lack of impairment of AChE after 2 h of incubation of the brain subfraction with methyl parathion and, alternatively, with NADPH, CO, SKF 525-A, piperonyl butoxide or nitrogen indicated that this brain subfraction transformed methyl parathion without the involvement of a mixed-function oxidative pathway. The results from HPLC analysis did not show a peak corresponding to methyl paraoxon (O,O-dimethyl O-p-nitrophenylphosphate), but showed the production of an unidentified peak which eluted nearby standard methyl parathion (retention times of 10.65 and 8.86 min, respectively). GC-MS analysis suggested that the unidentified product could be a methyl parathion isomer.
de Lima
J S
JS
Departamento de Bioquimica, UNIRIO, Rio de Janeiro, Brazil. jaime@dcc.001.cict.fiocruz.br
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D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000378:metabolism*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D007306:Insecticides / Q000493:pharmacokinetics*; D013058:Mass Spectrometry; D008743:Methyl Parathion / Q000493:pharmacokinetics*; D051381:Rats
D002800:Cholinesterase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007306:Insecticides; D008743:Methyl Parathion; D003577:Cytochrome P-450 Enzyme System; D000110:Acetylcholinesterase