Decrease in Hepatic Drug-Metabolizing Enzyme Activities after Removal of Rats from Pine Bedding
Abstract:Wood is often used as a contact bedding material for laboratory animals. It has been established that wood, particularly softwood, has the potential to induce hepatic drug-metabolizing enzymes. However, to the authors' knowledge, changes in enzyme activity after removal of animals from bedding have not been characterized. The purpose of the study reported here was to determine how hepatic ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities alter over time after removal of rats from pine bedding. Male rats, three to four months old, raised in cages containing pine bedding, were transferred to wire-bottomed cages. At various times thereafter (up to 84 days), groups of rats were euthanized and the liver was processed to obtain microsomes. The microsomal protein and total cytochrome P450 (CYP) content and enzyme activities were determined. Significant differences in total microsomal protein or total CYP values were not observed over the 84 days, but a decrease in ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylation activities was detected. For p-nitrophenol hydroxylation, the decrease was exponential, with a half-life of approximately nine days, whereas for ethoxyresorufin-O-deethylation, a rapid decrease in activity in the first week was followed by a reduced rate of decrease thereafter. Enzyme activities did not stabilize for at least six weeks. Researchers using laboratory animals should, therefore, be aware that it takes several weeks for enzyme activities to stabilize once animals are removed from the bedding.
Document Type: Research Article
Affiliations: School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand
Publication date: June 1, 2003
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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