Comparative activities of xenobiótic metabolizing enzymes in sheep liver and small intestinal mucosas

Abstract

Intestinal mucosa has the ability to metabolize a great number of xenobiotics by both phase 1 and phase 2 reactions. The objective of this work was to evaluate xenobiotic metabolizing enzyme activities in cytosolic and microsomal fractions obtained from sheep liver and small intestine mucosas (duodenum, jejunum and ileum). Oxidative (cytochrome P450- dependent), reductive (carbonyl reductase) and enzymatic conjugative activities were measured by using known marker substrates. Metabolic activities measured in liver subcellular fractions were used as reference values. Intestinal Ndemethylase P450-dependent activities ranged between 11.0- 46.1 % (P450 3A) and 3.0-7.1 % (P450 2C) than those measured in the liver. These metabolic activities did not decrease nor increase along the small intestine. Conversely, microsomal O-deethylase P450-dependent activities (CYP 1A) were not detected in sheep small intestine mucosas. Intestinal carbonyl reductase activities were 14.3-23.4 % (microsomes) and 18.7-33.1 % (cytosol) than those measured in the liver. Intestinal microsomes were able to conjugate 1-naphthol, (an UGT-mediated reaction) and 1-cloro,2,4-dinitrobenzene (a GST probe). Metabolic reactions, taking place in the intestinal mucosa, may contribute to the pre-systemic metabolism of orally administered drugs. These results contribute to further current knowledge on the extra-hepatic biotransformation pathways in ruminants.