Selective alteration of constitutive hepatic cytochrome P-450 enzymes in the rat during parenteral hyperalimentation

Biochemical Pharmacology
R G KnodellF P Guengerich

Abstract

Decreased drug metabolism and hepatic cytochrome P-450 levels have been shown previously to occur in rats receiving total parenteral nutrition (TPN) compared to animals receiving the same hyperalimentation solution enterally (TEN). In the present studies, animals received a 7-day infusion of a 25% glucose-2.75% crystalline amino acid solution via a catheter in the jugular vein or stomach; hepatic microsomal levels of four major constitutive cytochromes P-450 were determined subsequently by immunoquantitation and correlated with metabolism of selected substrates biotransformed by these enzymes. TPN resulted in a marked decrease in apoprotein of two constitutive cytochromes P-450, P-450UT-A and P-450PCN-E, compared to TEN experiments (for P-450UT-A, 11.0 +/- 1.8 vs 44.7 +/- 6.5% of total cytochrome P-450 measured by CO-difference spectra, P greater than 0.001; for P-450PCN-E, 15.4 +/- 4.4 vs 30.2 +/- 7.6%, P less than 0.01), but apoprotein levels of two other constitutive cytochromes P-450, P-450PB-C and P-450UT-F, showed relatively little change. Concordant reductions in metabolism of benzphetamine, ethylmorphine and erythromycin were seen in TPN animals. While the mechanisms responsible for these selective changes in the synthe...Continue Reading

References

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Citations

Jun 1, 1996·Nutrition·F JorqueraJ González-Gallego
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·John R Cashman, Jun Zhang
Sep 12, 2002·Pharmacotherapy·Roland N Dickerson, Scott L Charland
Sep 1, 1994·JPEN. Journal of Parenteral and Enteral Nutrition·G I Earl-Salotti, S L Charland
Jun 1, 1995·Journal of the American College of Nutrition·E R Briones, F L Iber
Jan 17, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew A ShawRaymond E Galinsky
Jan 28, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·John R CashmanJing Lin

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