Hepatic and intestinal CYP3A expression and activity in broilers

Abstract

Cytochrome P450 is involved in drug metabolism. Subfamily CYP3A shows a degree of similarity across different animal species. However, little information is available about its expression and activity in broiler chickens. A RT-PCR method was developed for the quantification of CYP3A37 expression in the liver and small intestine of broilers. A higher expression in the jejunum was observed compared with that in the ileum. In the liver, a significantly lower expression compared with that in the jejunum was noticed. Thus, the role of the small bowel in drug metabolism cannot be neglected in broilers. CYP3A activity was studied in vitro using midazolam as a substrate. Two protocols for the preparation of intestinal microsomes were compared. Mincing of the tissues before ultracentrifugation seemed to be more appropriate than a protocol based on ethylenediaminetetra-acetic acid separation. CYP3A activity revealed to be the highest in the duodenum with a decreasing trend towards the ileum. Activity in liver was comparable to duodenal activity.

Characterization of Porcine Hepatic and Intestinal Drug Metabolizing CYP450: Comparison with Human Orthologues from A Quantitative, Activity and Selectivity Perspective

“…Previously it has been shown that the elution of intestinal samples with EDTA resulted in the highest CYP450 activity when compared to the mucosal scraping method 68 . Furthermore, in the comparison between the EDTA elution method and the mincing method, it was shown that the latter resulted in higher enzymatic activities and more reproducible results 69 . Hence the mincing method was used in the current study.…”