1 The metabolism of 2-ethylhexanoic acid (2-EHA) was studied in rat, mouse and human liver microsomes in vitro.
The metabolites of 2-EHA were identified as methylated derivatives by gas chromatography-mass spectrometry. 2 2-Ethyl-1,6-hexanedioic acid was the main metabolite produced in rat, mouse and human liver microsomes.
Unsaturated 2-ethyl-5-hexenoic acid, a terminal olefin, was produced only in human liver microsomes and phenobarbital-induced rat liver microsomes.
The cytochrome P450 (CYP) inhibitors metyrapone, SKF 525A, triacetyloleandomycin (TAO), quinidine and the cytochrome P450 reductase antibody abolished its formation both in rat and human microsomes. 3 The metabolites were analyzed also in vivo in urine of 2-EHA-exposed rats and in urine of sawmill workers exposed occupationally to 2-EHA.
Both rat and human urine contained 2-ethyl-1,6-hexanedioic acid as the main metabolite and also 2-ethyl-5-hexenoic acid.
Metyrapone, SKF 525A and TAO all decreased drastically the formation of 2-ethyl-5-hexenoic acid in the rat. 4 The data indicate that (1) several CYP families (CYP2A, CYP2B, CYP2D and CYP3A) could be responsible for the hepatic metabolism of 2-EHA, (2) the same metabolites were formed in rats and man and (3) an unsaturated terminal olefin, 2-ethyl-5-hexenoic acid is formed in the liver.
Mots-clés Pascal : Métabolisme, In vitro, Rat, Rodentia, Mammalia, Vertebrata, Souris, Homme, Foie, Microsome, Oléfine, In vivo, Exposition professionnelle, Urine, Médecine travail, Cytochrome P450, Isozyme, Hexanoïque acide(2-éthyl)
Mots-clés Pascal anglais : Metabolism, In vitro, Rat, Rodentia, Mammalia, Vertebrata, Mouse, Human, Liver, Microsome, Olefin, In vivo, Occupational exposure, Urine, Occupational medicine, Cytochrome P450, Isozyme
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Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0262888
Code Inist : 002B03L06. Création : 199608.