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Updated: Jul 15, 2026

An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment
Published on: April 20, 2018
Effects of bedding substrates on microsomal enzymes in rabbit liver
Dawn Ruben1, Nicole Muratore, Scott Pin
1Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Abstract:
Previous studies have reported that housing rats and mice on softwood beddings induce microsomal enzymes. To date, no published studies investigate effects of softwood beddings on microsomal induction in rabbits. The purpose of this study was to determine whether microsomal enzymes, primarily cytochromes P450 3A and 2B, were induced in rabbits exposed to commonly used bedding substrates. Rabbits were placed in cages 7.6 cm above 1 sheet of 24 x 36 in. postconsumer recycled paper, approximately 16 cups (130 ounces) of pine shavings, or no substrate. Positive-control rabbits were given either rifampin (50 mg/kg) or phenobarbital (60 mg/kg) intraperitoneally once daily for 5 d. At 2, 7, and 14 d after placement in test cages, rabbits were euthanized and the livers harvested. Microsomal pellets were prepared from the livers and used in an erythromycin Ndemethylase assay (to determine CYP3A activity) and a pentoxyresorufin-O-deethylation assay (to determine CYP2B activity). Although the levels of enzyme induction varied slightly in both assays, statistical significance was not reached compared to the positive-control levels. These results indicate that neither CYP450 3A or 2B enzymes are induced by exposure of rabbits to pine shavings or paper substrate as noncontact bedding for up to 14 d.
Insights
Pine shavings and paper bedding do not induce cytochrome P450 (CYP450) enzymes in rabbits. This study found no significant changes in CYP450 3A or 2B activity when rabbits were housed on these common substrates.
Area of Science:
- Pharmacology
- Toxicology
- Animal Science
Background:
- Softwood beddings are known to induce microsomal enzymes in rodents.
- Limited research exists on the effects of bedding substrates on microsomal enzyme induction in rabbits.
- Cytochrome P450 (CYP450) enzymes, particularly CYP3A and CYP2B, are crucial for drug metabolism.
Purpose of the Study:
- To investigate whether common bedding substrates (pine shavings, recycled paper) induce CYP450 3A and 2B enzymes in rabbits.
- To assess the impact of noncontact bedding exposure on hepatic microsomal enzyme activity in rabbits.
Main Methods:
- Rabbits were housed on pine shavings, recycled paper, or no substrate for up to 14 days.
- Positive controls received intraperitoneal rifampin or phenobarbital to induce CYP450 enzymes.
- Liver microsomes were analyzed for CYP3A and CYP2B activity using specific enzyme assays.
Main Results:
- No statistically significant induction of CYP450 3A or 2B enzymes was observed in rabbits exposed to pine shavings or paper bedding.
- Enzyme activity levels in rabbits on bedding substrates did not reach the levels seen in positive controls.
- Exposure to pine shavings or paper as noncontact bedding did not significantly alter key drug-metabolizing enzymes.
Conclusions:
- Pine shavings and recycled paper, when used as noncontact bedding, do not induce CYP450 3A or 2B enzymes in rabbits.
- These findings suggest that common bedding materials are unlikely to significantly affect rabbit drug metabolism via these specific CYP450 pathways.
- Further research may explore longer exposure durations or different bedding types.
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