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 Vmax/Kmratios (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 2β- and 6β-hydroxytestosterone (CYP3A), and these metabolite formation rates were highly correlated (r = 0.865; p < 0.001). The formation rates for 2α- and 16α-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.
Footnotes
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↵1 Present address: Mylan Laboratories, 3711 Collins Ferry Road, Morgantown, WV 26505.
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Results from this work were presented in poster format at the International Society for the Study of Xenobiotics 10th North American Meeting, Indianapolis, IN, October 24, 2000 and have been published in abstract form in Drug Metab Rev (2000) 32:225 (Abstract 177).
- Abbreviations used are::
- TPN
- total parenteral nutrition
- MDZ
- midazolam
- P450
- cytochrome P450
- HPLC
- high-performance liquid chromatography
- Received July 31, 2001.
- Accepted November 1, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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