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Decrease in hepatic drug-metabolizing enzyme activities after removal of rats from pine bedding.

Andrew Keith Davey1, John Paul Fawcett, Soo Eng Lee

  • 1School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand.

Comparative Medicine
|July 19, 2003
PubMed
Summary
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Laboratory rats removed from pine bedding show altered hepatic enzyme activities for weeks. Drug-metabolizing enzyme levels, specifically ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation, take over six weeks to stabilize post-bedding removal.

Area of Science:

  • Pharmacology
  • Toxicology
  • Animal Science

Background:

  • Wood bedding, especially softwood, is known to induce hepatic drug-metabolizing enzymes in laboratory animals.
  • Changes in these enzyme activities after removal from wood bedding have not been well-characterized.

Purpose of the Study:

  • To investigate the time-dependent alterations in hepatic ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities in rats after transfer from pine bedding.

Main Methods:

  • Male rats were housed on pine bedding and then transferred to wire-bottomed cages.
  • Liver microsomes were collected at various time points up to 84 days.
  • Microsomal protein, total cytochrome P450 (CYP) content, and specific enzyme activities were quantified.

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Main Results:

  • No significant changes in total microsomal protein or total CYP content were observed over 84 days.
  • A notable decrease in both ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities was detected.
  • P-nitrophenol hydroxylation showed an exponential decrease with a half-life of approximately nine days; ethoxyresorufin-O-deethylation decreased rapidly initially, then slowed.

Conclusions:

  • Hepatic enzyme activities in rats do not rapidly return to baseline after removal from pine bedding.
  • Enzyme activities remained altered for at least six weeks, indicating a prolonged effect.
  • Researchers must consider this extended stabilization period when designing experiments with laboratory animals previously housed on wood bedding.