Fluconazole alters CYP26 gene expression in mouse embryos.
Disruption of embryonal retinoic acid homeostasis has been postulated to represent an etiological factor involved in the onset of fluconazole-induced teratogenesis. In the present study the impact of a teratogenic pulse of fluconazole on the gene expression of cytochrome P450 (CYP) 26 isoforms, which plays a central role in maintaining proper retinoic acid levels by mediating its degradation, was investigated. ICR pregnant mice were orally administered with 0 (vehicle) or 700mg/kg of fluconazole on gestation day 8. Embryos were collected 12, 24 and 48h after treatment. Quantitative real-time reverse-transcription polymerase chain reaction (quantitative real-time RT-PCR) assay was used to quantify the mRNA expression of CYP26a1, CYP26b1 and CYP26c1 in embryos. As result, fluconazole exposure was associated to an up-regulation of CYP26a1, CYP26b1, whereas no significant change was identified for the CYP26c1 isoform. This study demonstrates the capacity of fluconazole to alter CYP26 gene expression in mouse embryos.
Tiboni
Gian Mario
GM
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università G. d'Annunzio di Chieti-Pescara, Italy. tiboni@unich.it
Marotta
Francesca
F
Carletti
Erminia
E
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D000072500:Cytochrome P450 Family 26; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000378:metabolism
D000935:Antifungal Agents; D012333:RNA, Messenger; D014212:Tretinoin; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; C000607081:Cyp26b1 protein, mouse; C495026:Cyp26c1 protein, mouse; D000072500:Cytochrome P450 Family 26; D000072516:Retinoic Acid 4-Hydroxylase