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Ontogeny of CYP 3 A and P ‐Glycoprotein in the Liver and the Small Intestine of the Göttingen Minipig: An Immunohistochemical Evaluation
Author(s) -
Van Peer Els,
Verbueken Evy,
Saad Moayad,
Casteleyn Christophe,
Van Ginneken Chris,
Van Cruchten Steven
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12173
Subject(s) - ontogeny , cyp3a , biology , immunohistochemistry , cytochrome p450 , p glycoprotein , jejunum , small intestine , pathology , endocrinology , immunology , biochemistry , medicine , metabolism , antibiotics , multiple drug resistance
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 ( P gp) and the metabolizing cytochrome P 450 ( CYP ) 3 A subfamily in the livers (n = 115) and the small intestines (n = 74) of foetal, neonatal, juvenile and adult G öttingen minipigs. P gp was expressed in the liver in all age groups, whereas its presence in the jejunum was detected from 86 days of gestation onwards. Low expression of CYP 3 A was detected in the jejunums and livers from foetal and neonatal piglets. During postnatal development, the immunoreactivity for CYP 3 A increased in both organs. A centrilobular pattern, with a more intense staining for CYP 3 A 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 CYP 3 A in minipigs corresponds to that in man, in which a similar spatio‐temporal expression has been reported.