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Effects of Low and High Protein Diets on the Induction of Microsomal Drug-metabolizing Enzymes in Rat Liver^1,2,

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

To determine the effect of low and high levels of dietary proteins plus low doses of phenobarbital (PB) on the induction of drug-metabolizing enzymes, weanling male and female Sprague-Dawley rats were fed, ad libitum, diets containing 3.5 (low protein, LP), 26 (normal protein, NP), and 42% (high protein, HP) casein for 33 days. Five animals from each dietary group were injected with 10 mg of PB/kg body weight, intraperitoneally, for the last 3 days of the experimental period. The 10,000 x g supernatant and microsomes were prepared from perfused livers from each group. Both LP and HP diets caused a significant decrease in the activity of biphenyl 4-hydroxylase, an increase in the activity of p-nitrobenzoate reductase, and no changes in the activities of 4-methylumbelliferone glucuronyltransferase and cytochrome P-450. The low doses of PB used in this study caused significant induction of cytochrome P-450 (P < 0.10), biphenyl 4-hydroxylase, and p-nitrobenzoate reductase (except in LP and NP females). The males of NP and HP groups had consistently higher activities of these enzymes than corresponding females, however, this sex difference in the first two enzymes was abolished by feeding of the LP diet.

KEY WORDS: • low protein • high protein • drug metabolism • microsomal enzymes • biphenyl hydroxylase • nitroreductase • glucuronyltransferase

¹ This investigation was supported by National Institute of General Medical Sciences grant no. 5 PO1 GM17806.

² Preliminary results of this investigation were reported at the annual meeting of the Federation of American Societies for Experimental Biology, Atlantic City, N.J., 1974. Federation Proc. 33, 696. (Abstr.)

Manuscript received 20 January 1975.