The in vitro metabolism of a pyrethroid insecticide, permethrin, and its hydrolysis products in rats.
The in vitro metabolism of permethrin and its hydrolysis products in rats was investigated. Cis- and trans-permethrin were mainly hydrolyzed by liver microsomes, and also by small-intestinal microsomes of rats. trans-Permethrin was much more effectively hydrolyzed than the cis-isomer. When NADPH was added to the incubation mixture of the liver microsomes, three metabolites, 3-phenoxybenzyl alcohol (PBAlc), 3-phenoxybenzaldehyde (PBAld) and 3-phenoxybenzoic acid (PBAcid), were formed. However, only PBAlc was formed by rat liver microsomes in the absence of cofactors. The microsomal activities of rat liver and small intestine were inhibited by bis-p-nitrophenyl phosphate, an inhibitor of carboxylesterase (CES). ES-3 and ES-10, isoforms of the CES 1 family, exhibited significant hydrolytic activities toward trans-permethrin. When PBAlc was incubated with rat liver microsomes in the presence of NADPH, PBAld and PBAcid were formed. The NADPH-linked oxidizing activity was inhibited by SKF 525-A. Rat recombinant cytochrome P450, CYP 2C6 and 3A1, exhibited significant oxidase activities with NADPH. When PBAld was incubated with the microsomes in the presence of NADPH, PBAcid was formed. CYP 1A2, 2B1, 2C6, 2D1 and 3A1 exhibited significant oxidase activities in this reaction. Thus, permethrin was hydrolyzed by CES, and PBAlc formed was oxidized to PBAld and PBAcid by the cytochrome P450 system in rats.
Nakamura
Yuri
Y
Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Hiroshima 734-8551, Japan.
Sugihara
Kazumi
K
Sone
Tomomichi
T
Isobe
Masakazu
M
Ohta
Shigeru
S
Kitamura
Shigeyuki
S
D000818:Animals; D001547:Benzaldehydes / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism; D001592:Benzyl Alcohols / Q000378:metabolism; D043182:Carboxylesterase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006867:Hydrolases / Q000378:metabolism; D006868:Hydrolysis; D007306:Insecticides / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D010084:Oxidation-Reduction; D026023:Permethrin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001547:Benzaldehydes; D001565:Benzoates; D001592:Benzyl Alcohols; D007306:Insecticides; C064809:3-phenoxybenzylalcohol; C064808:3-phenoxybenzaldehyde; D026023:Permethrin; C017618:3-phenoxybenzoic acid; D003577:Cytochrome P-450 Enzyme System; D006867:Hydrolases; D043182:Carboxylesterase