Vol. 30, Issue 2, 177-182, February 2002

The Influence of L-Glutamine on the Depression of Hepatic Cytochrome P450 Activity in Male Rats Caused by Total Parenteral Nutrition

Andrew A. Shaw,¹ Stephen D. Hall, Michael R. Franklin, and Raymond E. Galinsky

Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana (A.A.S., R.E.G.); Division of Clinical Pharmacology, Department of Medicine, Indiana University, Indianapolis, Indiana (S.D.H., R.E.G.); and Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, Utah (M.R.F.)

Total parenteral nutrition (TPN) bypasses the gut leading to intestinal and hepatic dysfunction, including decreased hepatic cytochrome P450 (P450) activity. Glutamine prevents the TPN-associated changes in gut function and morphology. This study examined the effect of glutamine supplementation on hepatic P450 activities in male Sprague-Dawley rats receiving continuous TPN. Animals received continuous lipid-free TPN for 7 days with 0, 0.1, or 4.5% glutamine. Surgical controls were allowed free access to rat chow. The V_max/K_m ratios (intrinsic clearance) for the formation of 4-hydroxymidazolam (CYP3A) were 12.8, 14.6, and 27.7 µl/min/mg for TPN treatment with 0, 0.1%, or 4.5% glutamine, respectively, compared with a chow-fed control (37.1 µl/min/mg). The corresponding values for 1'-hydroxymidazolam formation (CYP3A) were 3.7, 6.1, 11.7, and 15.2 µl/min/mg, respectively. The addition of glutamine to TPN similarly affected the formation rates for 2- and 6-hydroxytestosterone (CYP3A), and these metabolite formation rates were highly correlated (r = 0.865; p < 0.001). The formation rates for 2- and 16-hydroxytestosterone (CYP2C) were also highly correlated (r = 0.892; p < 0.001). Parenteral glutamine modified the TPN-associated suppression of CYP3A and CYP2C activities in adult male rats receiving TPN.