Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa.docVIP

BMC Clinical Pharmacology BioMedCentral Research article Open Access Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa Ina Bergheim*1,2, Christiane Bode1 and Alexandr Parlesak1 Address: 1Hohenheim University (140), Dep. Physiology of Nutrition, Stuttgart, Germany and 2Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, USA Email: Ina Bergheim* - ina.bergheim@freenet.de; Christiane Bode - bodech@uni-hohenheim.de; Alexandr Parlesak - parlesak@uni- hohenheim.de * Corresponding author Published: 27 October 2005 Received: 03 May 2005 Accepted: 27 October 2005 BMC Clinical Pharmacology 2005, 5:4 doi:10.1186/1472-6904-5-4 This article is available from: /1472-6904/5/4 ? 2005 Bergheim et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Despite the fact that the alimentary tract is part of the bodys first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon. Methods: Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods. Results: Extensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2