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Induction of Microsomal Drug Metabolizing Enzymes by Oral Contraceptives in Protein-Malnourished Rats^1,2,

Department of Pharmacology, Meharry Medical College, Nashville, Tennessee 37208

In order to examine effects of oral contraceptives (OC) on the microsomal drug metabolizing enzymes in a state of protein malnutrition, weanling Sprague-Dawley female rats were fed diets containing 3.5% (low protein, LP), 26% (normal protein, NP) or 42% (high protein, HP) casein for 224 days and norethynodrel plus mestranol for the last 182 days. LP rats were smaller in body weight than NP and HP rats and the latter two groups showed depressed weight gain and hypertrophy of liver and kidney due to OC. Concentrations of microsomal proteins and cytochrome P-450 were lowered by LP diet and OC did not induce cytochrome P-450. Activity of biphenyl-4-hydroxylase was lowered in LP and HP rats compared to NP group in which activity of this enzyme was significantly decreased due to OC. The diets alone had no effect on the activity of p-nitrobenzoate reductase, however, its activity was enhanced by OC only in NP rats. LP diet caused reduction of 4-methylumbelliferone glucuronyl transferase activity which was lowered by OC in NP as well as in LP rats. It is concluded that NP diet more than either LP or HP diet exposed rats to the modification of microsomal drug metabolizing enzymes by OC.

KEY WORDS: • protein-malnutrition • oral contraceptives • drug metabolism • microsomal enzymes

¹ This investigation was supported by GRSG 5-S01-RR05422-13 and NIGMS grant 5 P01 GM17806.

² Preliminary report of these results was presented at the annual fall meeting of the American Society for Pharmacology and Experimental Therapeutics, Davis, Calif. 1975. The Pharmacologist 17, 231 (Abstr.).

³ Present address: Medical Research Service, VA Hospital, 10701 East Boulevard, Cleveland, Ohio 44106.

Manuscript received 23 January 1976.