Investigation of the effect of butyrate supplementation of the diet on hepatic cytochrome P450 enzymes in rats

Orally applied butyrate as a nutritional supplement has a huge impact on the health of the gastrointestinal epithelium and the gut microflora. In addition, as an epigenetically active molecule, it can also influence the expression of certain genes. Regarding the results of some in vitro studies, butyrate, absorbed from the intestines and taken to the liver by the portal circulation, may alter the action of hepatic microsomal cytochrome P450 (CYP) enzymes, involved in the biotransformation of xenobiotics, having a remarkable importance in food safety, as well. The authors aimed to study the possible effects of orally applied butyrate on hepatic CYP activity in rats after weaning, also serving as a monogastric mammalian model. Animals were fed with normal pelleted stock diet without or with sodium butyrate (1.5 g/kg diet) for 21 days. As a positive control, a group of rats was treated with intraperitoneal phenobarbital injection. Animals were euthanized on day 21, microsomal fractions were separated from the exsanguinated livers by differential centrifugation. The activity of the most important (VP subfamilies was screened by specific enzyme assays (aminopyrine N-demethylation: CYP2B/3A, testosterone 6 beta-hydroxylation: CYP3A). According to the results, butyrate as a feed supplement did not cause any changes in the drug-metabolising activity of the examined hepatic microsomal CYP enzymes. However, phenobarbital significantly (P<0,05) increased the microsomal CYP2B and CYP3A activity of the liver. These data indicate that the supplementation of the diet with butyrate probably may not have any pharmacokinetic interactions with simultaneously applied xenobiotics in monogastric mammals, so it can be applied safely as a nutritional supplement.