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The effect of sepsis during parenteral nutrition on hepatic microsomal function in rats
Roland N Dickerson1, Scott L Charland
1Department of Pharmacy, University of Tennessee Health Science Center, Memphis 38163, USA.
Study Objective:
To investigate the effect of sepsis during parenteral nutrition on hepatic cytochrome P450 (CYP) activity in rats.
Design:
Prospective, randomized, controlled study.
Setting:
University-based animal research laboratory.
Animals:
Twenty adult male Sprague-Dawley rats.
Intervention:
The animals were cannulated intravenously and randomized to receive parenteral nutrition (PN), intravenous live Escherichia coli 4 x 10(8) colony-forming units/100 g body weight for 2 consecutive days with PN (PNEC), or chow (CH).
Measurements And Main Results:
Both PN alone and PNEC resulted in a progressive decline in hepatic CYP concentration compared with CH (0.53 +/- 0.10, 0.41 +/- 0.17, and 0.35 +/- 0.14 nmol/mg microsomal protein, respectively, p < 0.05). Parenteral nutrition alone was associated with a 57% decrease in isoenzyme ethoxycoumarin-O-deethylase activity (ECOD) compared with CH, but sepsis did not further decrease ECOD activity any more than PN alone (0.103 +/- 0.049, 0.044 +/- 0.018, and 0.050 +/- 0.020 nmol/mg microsomal protein/min, respectively, p < 0.05).
Conclusion:
Hepatic CYP concentration declines with PN and is further decreased when compounded by sepsis. The disproportional decrease in ECOD activity relative to CYP concentration with PN is unchanged by sepsis, indicating a selective alteration in hepatic isoenzymes by PN.