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Estradiol induced vaginal cornification in spayed rats: a model to study hepatic microsomal enzyme induction
T V Shanbhag1, K L Bairy, D R Kulkarni
1Department of Pharmacology, Kasturba Medical College, Manipal.
Indian Journal of Physiology and Pharmacology
|January 1, 1989
Summary
This study shows that vaginal cornification in rats can measure how liver enzymes affect drug metabolism. Enzyme induction significantly increased the estradiol dose needed, suggesting this model can replace traditional tests for enzyme induction.
Area of Science:
- Pharmacology
- Endocrinology
- Toxicology
Background:
- Estradiol undergoes hepatic first-pass metabolism.
- Liver enzyme activity influences drug efficacy.
- Rifampin is a known inducer of hepatic enzymes.
Purpose of the Study:
- To evaluate estradiol's median cornification dose (cED50) in spayed rats.
- To assess the impact of enzyme induction by rifampin on estradiol's cED50.
- To determine if vaginal cornification bioassay can model hepatic enzyme activity.
Main Methods:
- Bioassay using vaginal cornification response in spayed rats.
- Administration of estradiol via intraperitoneal (ip) and subcutaneous (sc) routes.
- Comparison of cED50 with and without rifampin-induced enzyme activity.
Main Results:
- Enzyme induction by rifampin increased the cED50 of estradiol fourfold.
- The ratio of ip cED50 to sc cED50 doubled after enzyme induction.
- The animal model demonstrated sensitivity to altered hepatic enzyme activity.
Conclusions:
- Vaginal cornification bioassay accurately reflects changes in hepatic enzyme activity.
- This model serves as a viable alternative to the hexobarbitone sleeping time test for studying enzyme induction.