Effects of hypothermia and hypoxia on cytochrome P450-mediated drug metabolism in neonatal Göttingen minipigs.
Göttingen minipigs
cytochrome P450
hypothermia
hypoxia
neonatal
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
24 Sep 2024
24 Sep 2024
Historique:
revised:
14
08
2024
received:
21
05
2024
accepted:
06
09
2024
medline:
24
9
2024
pubmed:
24
9
2024
entrez:
24
9
2024
Statut:
aheadofprint
Résumé
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 Göttingen minipigs, alongside those from an (non-survival) in vivo study, where four conditions-control (C), therapeutic hypothermia (TH), hypoxia (H), hypoxia and TH (H + TH)-were examined. Naive neonatal Göttingen minipigs exhibited 75% lower general CYP activity and different gene expression patterns than adults. In vitro hypothermia (33°C) decreased general CYP activity in adult liver microsomes by 36%. Gene expression was not different between TH and C while hypoxia up-regulated several genes (i.e., CYP3A29 [expression ratio; E
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Research Scientific Foundation-Flanders
ID : G0D0520N
Organisme : Herculesstichting
ID : AUHA/13/006
Informations de copyright
© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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