Authors : Sung-Won Park, Hee Yi, Soo-Min Cho, Kyul Jo, Jin-A Park, Soo-Jean Shin, Hee-Jung Cho, Si-Whan Song, Sang Min Jeong and Ho-Chul Shin
Abstract: This study was performed to set up a transcriptional database of the intestinal metabolizing enzymes in beagle dogs. The total RNA was isolated from the duodenum and the mRNA expression was measured using GeneChip® oligonucleotide arrays. Detected genes from the intestine were about 47% of 43, 035 sequences and total of 79 genes involved metabolizing enzymes. Among the phase I enzymes, dogs exhibited abundant gene expressions of CYP3A12, CYP2B11, LOC610195 (similar to CYP2J2) followed by LOC489851 (similar to CYP3A4), CYP27A1 and CYP51. For phase II enzymes, acetyltransferase ACAT1, glutathione S-transferases GSTA3 and GSTP1, sulfotransferases SULT1A1 and SULT1D, acyltransferases DGAT1 and ACAA1 and glucuronosyltransferase UGCG were highly expressed in duodenum. The dogs expression profiles were compared with those in mice based on gene classification and annotation. Between the two species, the regression of all enzymes (n = 36) with same annotations was 0.496 as andcoefficient of determination (R2) however, two cytochrome P450s including CYP2S1 and CYP4B1 were expressed <5 fold and phase II enzymes including GSTA3, SULT1A1, SULT1D1, TPST1 and UGCG were expressed >5 fold changes in dogs (t-test, p<0.01). In sum, theses data indicated significant differences between beagle dogs and ICR mice in the mRNA expression of both p450s and phase II metabolizing enzymes. These animals are the most widely used species/lines in toxicological and pharmacological screening. Therefore, this database will be useful for predicting and scaling the intestinal drug metabolism between rodents (mice) and non-rodents (dogs).
Sung-Won Park, Hee Yi, Soo-Min Cho, Kyul Jo, Jin-A Park, Soo-Jean Shin, Hee-Jung Cho, Si-Whan Song, Sang Min Jeong and Ho-Chul Shin, 2011. Gene Expression of Metabolizing Enzymes in Beagle Dog Intestine. Journal of Animal and Veterinary Advances, 10: 1947-1955.