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.