Effects of insecticide synergists on microsomal oxidation of estradiol and ethynylestradiol and on microsomal drug metabolism

Xenobiotica. 1976 Jan;6(1):33-8. doi: 10.3109/00498257609151609.


1. Oxidation of estradiol and ethynylestradiol at ring A and ring B by rat liver microsomes and NADPH-regenerating system in vitro is inhibited by the two arylimidazole insecticide synergists, 3-bromophenyl-4(5)-imidazole and 1-naphthyl-4(5)-imidazole, but not by the benzothiadiazole insectide synergists 6-nitro-1,2,3-benzothiadiazole and 5,6-dimethyl-1,2,3-benzothiadiazole. The Ki of the most potent inhibitor, 1-naphthyl-4(5)-imidazole, was 3 X 10(-6) M. 2. 6-Nitro-1,2,3-benzothiadiazole (10(-6) M), which did not inhibit hydroxylation of the estrogens, inhibited oxidation of aniline and demethylation of ethylmorphine, p-nitroanisole, and aminopyrine by 30-70%. 5,6-Dimethyl-1,2,3-benzothiadiazole inhibited only demethylation of p-nitroanisole and aminopyrine. From these results the presence of different hepatic microsomal mixed function oxidases may be inferred. 3. 1-Naphthyl-4(5)-imidazole, the most potent inhibitor of hydroxylation of drugs and estrogen rings A and B, also inhibited microsomal estrogen-16alpha-hydroxylation. 4. These data show that insecticide synergists may effect the breakdown of estrogenic hormones in the organism.

MeSH terms

  • Animals
  • Binding, Competitive
  • Estradiol / metabolism*
  • Ethinyl Estradiol / metabolism*
  • Imidazoles / pharmacology*
  • Kinetics
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism*
  • Pesticide Synergists / pharmacology*
  • Rats
  • Structure-Activity Relationship


  • Imidazoles
  • Pesticide Synergists
  • Ethinyl Estradiol
  • Estradiol