The effect of dietary protein levels on xenobiotic biotransformations in F344 male rats.

Diets containing protein levels of 8, 12, and 22% were fed for 14 days to Fischer 344 male weanling rats. Enzyme activities in liver and kidney were measured using several substrates for each of the following enzyme systems: Cytochrome P-450-dependent monooxygenase, ester hydrolysis, and conjugations with sulfate, glutathione, and glucuronic acid. Enzyme activities, for the various mechanisms, decreased from 15 to 65% with decreased dietary protein, with the exception of glucuronide and sulfate conjugation, which increased with decreased dietary protein. In vivo effects were evaluated by measuring hexobarbital sleeping time, procaine paralysis time, and bromobenzene hepatotoxicity. Increased dietary protein shortened hexobarbital sleeping time and procaine paralysis time, and increased procaine lethality, whereas low protein intake protected against bromobenzene hepatotoxicity. These data suggest that typical laboratory diets (22-25% protein) may provide artificially altered activities of xenobiotic biotransformation in rats, relative to nutritionally adequate (12% protein) diets.