{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:15:08Z","timestamp":1793830508846,"version":"4.6.1"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012541","name":"Herculesstichting","doi-asserted-by":"publisher","award":["AUHA\/13\/006"],"award-info":[{"award-number":["AUHA\/13\/006"]}],"id":[{"id":"10.13039\/501100012541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Asphyxiated neonates often undergo therapeutic hypothermia (TH) to reduce morbidity and mortality. As perinatal asphyxia and TH impact neonatal physiology, this could also influence enzyme functionality. Therefore, this study aimed to unravel the impact of age, hypothermia and hypoxia on porcine hepatic cytochrome P450 (CYP) gene expression, protein abundance and activity. Hepatic CYP expression, protein abundance and activity were assessed in naive adult and neonatal G\u00f6ttingen minipigs, alongside those from an (non\u2010survival) in vivo study, where four conditions\u2014control (C), therapeutic hypothermia (TH), hypoxia (H), hypoxia and TH (H\u2009+\u2009TH)\u2014were examined. Naive neonatal G\u00f6ttingen minipigs exhibited 75% lower general CYP activity and different gene expression patterns than adults. In vitro hypothermia (33\u00b0C) decreased general CYP activity in adult liver microsomes by 36%. Gene expression was not different between TH and C while hypoxia up\u2010regulated several genes (i.e., <jats:italic>CYP3A29<\/jats:italic> [expression ratio; <jats:italic>E<\/jats:italic><jats:sub><jats:italic>R<\/jats:italic><\/jats:sub>\u00a0=\u20095.1472] and CYP2C33 [<jats:italic>E<\/jats:italic><jats:sub><jats:italic>R<\/jats:italic><\/jats:sub>\u00a0=\u20093.2292] in the H group and CYP2C33 [<jats:italic>E<\/jats:italic><jats:sub><jats:italic>R<\/jats:italic><\/jats:sub>\u00a0=\u20092.4914] and CYP2C42 [<jats:italic>E<\/jats:italic><jats:sub><jats:italic>R<\/jats:italic><\/jats:sub>\u00a0=\u20094.0197] in the H\u2009+\u2009TH group). The medical treatment and the interventions over 24\u2009h, along with hypoxia and TH, affected the protein abundance. These data on CYP expression, abundance and activity in young animals can be valuable in building physiologically\u2010based pharmacokinetic models for neonatal drug dose predictions.<\/jats:p>","DOI":"10.1111\/bcpt.14081","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:08:44Z","timestamp":1727183324000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of hypothermia and hypoxia on cytochrome P450\u2010mediated drug metabolism in neonatal G\u00f6ttingen minipigs"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-9458","authenticated-orcid":false,"given":"Marina\u2010Stefania","family":"Stroe","sequence":"first","affiliation":[{"name":"Comparative Perinatal Development University of Antwerp  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"De Clerck","sequence":"additional","affiliation":[{"name":"ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Dhaenens","sequence":"additional","affiliation":[{"name":"ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel Si\u00e2n","family":"Dennis","sequence":"additional","affiliation":[{"name":"ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Deforce","sequence":"additional","affiliation":[{"name":"ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences Ghent University  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Carpentier","sequence":"additional","affiliation":[{"name":"Facility for Systems Biology Mass Spectrometry KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-7351","authenticated-orcid":false,"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"},{"name":"BioNotus GCV  Niel Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4931-6562","authenticated-orcid":false,"given":"Karen","family":"Leys","sequence":"additional","affiliation":[{"name":"Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Smits","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"},{"name":"Department of Pharmaceutical and Pharmacological Sciences KU Leuven  Leuven Belgium"},{"name":"Department of Hospital Pharmacy Erasmus MC  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Van Ginneken","sequence":"additional","affiliation":[{"name":"Comparative Perinatal Development University of Antwerp  Antwerp 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