Effects of bedding substrates on microsomal enzymes in rabbit liver

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 N-demethylase 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.