Effects of Dietary Protein Quality On Drug Metabolism in the Rat

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Abstract
To determine effects of dietary protein quality on drug metabolism, two groups of male weanling Sprague-Dawley rats were pair-fed gluten (group 1) and casein (group 2) diets containing 18% protein for 10 days. Feeding a gluten diet significantly reduced hepatic microsomal protein, cytochrome P-450 and drug metabolism in vivo and in vitro. In group 1, hexobarbital sleeping time was markedly prolonged and both ethylmorphine and aniline metabolism in hepatic 9,000 × g supernatant fractions were lowered. Prior treatment with diethylaminoethyl 2,2-diphenylvalerate · HCl (SKF 525-A) prolonged hexobarbital narcosis to a greater magnitude in group 2. Aniline metabolism in vitro was inhibited by SKF 525-A in group 2 but not in group 1. Phenobarbital (PB) pretreatment shortened hexobarbital sleeping time and increased ethylmorphine N-demethylation and aniline hydroxylation both in groups 1 and 2; the latter two reactions were much greater in group 2. Increase in drug metabolism by PB was accompanied by a parallel rise in microsomal protein and cytochrome P-450 with group 2 animals exhibiting relatively higher levels than group 1. These data indicate that drug metabolism and microsomal enzyme inhibition or induction in rats vary with the quality of dietary protein and the type of drug.