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Influence of hyperalimentation on rat hepatic microsomal fluidity and function.

R G Knodell¹, D I Whitmer, R T Holman

¹Division of Gastroenterology, University of Maryland/Baltimore VA Medical Center.

Gastroenterology

|May 1, 1990

Summary

Total parenteral nutrition alters rat liver microsomal membrane fluidity and lipid composition. However, these changes do not fully explain the observed decreases in hepatic drug metabolism during parenteral nutrition.

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Area of Science:

Biochemistry
Pharmacology
Hepatology

Background:

Parenteral nutrition (PN) can reduce hepatic drug metabolism compared to enteral nutrition or standard chow.
Hepatic microsomal membrane fluidity and lipid composition are known to affect liver enzyme activity.

Purpose of the Study:

To investigate the impact of parenteral and enteral nutrition on rat hepatic microsomal membrane fluidity and lipid composition.
To compare these changes with their effects on hepatic drug metabolism, specifically meperidine demethylase and ethoxyresorufin deethylase activities.

Main Methods:

Assessing hepatic microsomal membrane fluidity using fluorescence anisotropy.
Analyzing lipid composition of hepatic microsomes.
Measuring activities of drug-metabolizing enzymes (meperidine demethylase, ethoxyresorufin deethylase).
Comparing outcomes between rats receiving PN, enteral nutrition, and chow.

Main Results:

Both PN and enteral nutrition significantly decreased microsomal membrane fluidity.
PN significantly decreased meperidine demethylase activity, while enteral nutrition reduced ethoxyresorufin deethylase activity.
Supplementing PN with lipids normalized membrane fluidity and lipid profiles but did not restore meperidine demethylase activity.

Conclusions:

Parenteral and enteral nutrition induce significant alterations in the physical state and lipid composition of rat hepatic microsomal membranes.
These observed changes in membrane properties are not the primary cause of the altered hepatic drug metabolism during hyperalimentation.