The effect of sepsis during parenteral nutrition on hepatic microsomal function in rats.
OBJECTIVE
To investigate the effect of sepsis during parenteral nutrition on hepatic cytochrome P450 (CYP) activity in rats.


METHODS
Prospective, randomized, controlled study.


METHODS
University-based animal research laboratory.


METHODS
Twenty adult male Sprague-Dawley rats.


METHODS
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).


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).


CONCLUSIONS
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.
Dickerson
Roland N
RN
Department of Pharmacy, University of Tennessee Health Science Center, Memphis 38163, USA.
Charland
Scott L
SL
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism; D005526:Food, Formulated; D008111:Liver Function Tests; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010288:Parenteral Nutrition / Q000009:adverse effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000201:enzymology / Q000378:metabolism*
D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1