Ontogeny of CYP3A and P-Glycoprotein in the Liver and the Small Intestine of the Gottingen Minipig: An Immunohistochemical Evaluation

Despite the increasing use of the minipig as a non-rodent species in general and juvenile toxicity studies, knowledge on their biotransformation processes and their ontogeny is scarce. Such data are prerequisite for the correct interpretation of non-clinical studies in this species. Therefore, the aim of our investigation was to immunohistochemically document the presence of the drug transporter P-glycoprotein (Pgp) and the metabolizing cytochrome P450 (CYP) 3A subfamily in the livers (n=115) and the small intestines (n=74) of foetal, neonatal, juvenile and adult Gottingen minipigs. Pgp was expressed in the liver in all age groups, whereas its presence in the jejunum was detected from 86days of gestation onwards. Low expression of CYP3A was detected in the jejunums and livers from foetal and neonatal piglets. During postnatal development, the immunoreactivity for CYP3A increased in both organs. A centrilobular pattern, with a more intense staining for CYP3A of the hepatocytes surrounding the central vein, was noticed in the postnatal livers. In conclusion, the presented data suggest that the intestinal and hepatic ontogeny of P-glycoprotein and CYP3A in minipigs corresponds to that in man, in which a similar spatio-temporal expression has been reported.