Differential induction of hepatic drug-metabolizing enzymes by fenvaleric acid in male rats

Toxicol Sci. 1999 Dec;52(2):148-53. doi: 10.1093/toxsci/52.2.148.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology*
  • Blotting, Western
  • Body Weight / drug effects
  • Clofibric Acid / toxicity
  • Cytochrome P-450 Enzyme System / metabolism
  • Enzyme Induction / drug effects*
  • Insecticides / pharmacology*
  • Liver / enzymology*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Nitriles
  • Organ Size / drug effects
  • Oxidation-Reduction
  • Peroxisomes / drug effects
  • Peroxisomes / enzymology
  • Pharmaceutical Preparations / metabolism*
  • Pyrethrins / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Stereoisomerism

Substances

  • Anticholesteremic Agents
  • Insecticides
  • Nitriles
  • Pharmaceutical Preparations
  • Pyrethrins
  • Clofibric Acid
  • Cytochrome P-450 Enzyme System
  • fenvalerate