title: The influence of L-glutamine on the depression of hepatic cytochrome P450 activity in male rats caused by total parenteral nutrition.
abstract: 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 microl/min/mg for TPN treatment with 0, 0.1%, or 4.5% glutamine, respectively, compared with a chow-fed control (37.1 microl/min/mg). The corresponding values for 1'-hydroxymidazolam formation (CYP3A) were 3.7, 6.1, 11.7, and 15.2 microl/min/mg, respectively. The addition of glutamine to TPN similarly affected the formation rates for 2beta- and 6beta-hydroxytestosterone (CYP3A), and these metabolite formation rates were highly correlated (r = 0.865; p < 0.001). The formation rates for 2alpha- and 16alpha-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.
authors.affiliation: Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Shaw
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hall
authors.forename: Michael R
authors.initials: MR
authors.lastname: Franklin
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Galinsky
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005973:Glutamine / Q000008:administration & dosage / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010288:Parenteral Nutrition / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism
chemical_list: D005973:Glutamine; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System