Veterinary session

Butyrate, dietary supplemented and also produced by the anaerobic bacterial fermentation has variable influences on the function of different cell types. As an epigenetically active molecule, butyrate can inhibit the histone deacetylase enzyme, causing histone hyperacetylation in vitro and also in vivo. It may modify the trascription of certain genes, such as those of hepatic microsomal cytochrome P450 (CYP) enzymes of primary cultured hepatocytes. Alterations of CYP expression have an effect on the detoxification capacity of the liver, influencing also the biotransformation of xenobiotics. On the basis of these data we can hypothesise that butyrate may also have an impact on the activity of different CYP enzymes in vivo.

Two experimental animal studies were carried out with broiler chickens of the Ross 308 strain in the early post-hatch period. In the first trial, animals were fed with starter diet without or with sodium butyrate (1.5 g/kg feed) for 24 days. In our second experiment, broilers were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day) for five days (days 20-24). As a positive control, in order to validate the model, a group of chicks was treated by intracoelomal phenobarbital injection (80 mg/kg body weight) in both experiments.

After slaughtering the animals on day 24, both studies were conducted on the same way. Livers were exsanguinated by chilled physiological saline solution and microsomal fractions were separated by differential centrifugation. The activity of CYP2H and CYP3A subfamilies, the most important enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions, KM and Vmax values were also determined.

According to our results, butyrate did not cause any changes in the drug-metabolising activity of hepatic microsomal CYP2H and CYP3A enzymes, neither as a nutritional supplement nor in bolus. However, phenobarbital significantly increased the microsomal aminopyrine N-demethylation and aniline-hydroxylation activity of the liver.

We can conclude that the orally applied butyrate did not influence the activity of the examined CYP enzymes. These data indicate that the supplementation of the diet with butyrate probably may not have any pharmacokinetic interactions with simultaneously applied xenobiotics.