Differential induction of hepatic drug-metabolizing enzymes by fenvaleric acid in male rats.
Racemic fenvaleric acid [2-(4-chlorophenyl)-3-methyl-butanoic acid], the principal metabolite of fenvalerate, was administrated orally at 0.75, 1.5, and 3.0 mmol/kg body weight/day to Fisher-344 male rats for 7 days. Both pure enantiomers of fenvaleric acid were administered at 1.5 mmol/kg body weight/day; the clofibric acid at the same concentration was used as a positive control. Hepatic enzyme activities were measured. Results obtained clearly show that fenvaleric acid induced numerous hepatic drug metabolism enzymes in F344 rats. The (R) enantiomer of this compound induces a proliferation of peroxisomes, whereas the (S) enantiomer induces CYP2B and mEH activities. Therefore, high exposure to pyrethroid insecticides could interact with the normal metabolism of drugs or xenobiotics.
Morisseau
C
C
Department of Entomology, University of California, Davis 95616, USA.
Derbel
M
M
Lane
T R
TR
Stoutamire
D
D
Hammock
B D
BD
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002995:Clofibric Acid / Q000633:toxicity; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects*; D007306:Insecticides / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009570:Nitriles; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000187:drug effects / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013237:Stereoisomerism
D000924:Anticholesteremic Agents; D007306:Insecticides; D009570:Nitriles; D004364:Pharmaceutical Preparations; D011722:Pyrethrins; D002995:Clofibric Acid; D003577:Cytochrome P-450 Enzyme System; C017690:fenvalerate