Effects of Insecticide Synergists on Microsomal Oxidation of Estradiol and Ethynylestradiol and on Microsomal Drug Metabolism

Abstract

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 insecticide synergists 6-nitro-l,2,3-benzothiadiazole and 5,6-dimethyl-l,2,3-benzothiadiazole. The K₁ of the most potent inhibitor, l-naphthyl-4(5)-imidazole, was 3 × 10-⁶ M.

2. 6-Nitro-1,2,3-benzothiadiazole (10-⁴ m), which did not inhibit hydroxyla-tion of the estrogens, inhibited oxidation of aniline and demethylation of ethyl-morphine, P-nitroanisole, and aminopyrine by 30–70%. 5,6-Dimethyl-l,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-16α-hydroxylation.

4. These data show that insecticide synergists may affect the breakdown of estrogenic hormones in the organism.