Molecular aspects of azoles-induced teratogenesis.
BACKGROUND
Antifungal azole compounds are widely used as antimycotics in plant, veterinary and human therapies. Their pharmacological action is based on the inhibition of the CYP450 enzyme catalyzing the synthesis of steroids required for the synthesis and integrity of fungal cell wall. Azoles are teratogenic in animal models and are under investigation for potential human developmental toxic effects. Rational approaches to prevent teratogenic effects require knowledge of the underlying mechanisms.


METHODS
This review highlights the current knowledge on the molecular mechanisms that are potentially involved in the teratogenic response to azoles.


RESULTS
A comprehensive review of the literature on this subject including experimental and clinical studies. Particular attention is focused on the mechanistic role played by CYP26 family inhibition.


CONCLUSIONS
Significant advancements have been made in the comprehension of molecular mechanisms underlying teratogenic effects mediated by azole derivatives. Increasing evidence is linking disruption of embryonic retinoic acid homeostasis as a crucial determinant of azole-mediated teratogenesis.
Marotta
Francesca
F
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Facoltà di Medicina e Chirurgia, Università G. d'Annunzio Chieti-Pescara, Ospedale SS. Annunziata, Via dei Vestini, 66013 Chieti, Italy.
Tiboni
Gian Mario
GM
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects; D001393:Azoles / Q000009:adverse effects*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D011247:Pregnancy; D000072516:Retinoic Acid 4-Hydroxylase
D000935:Antifungal Agents; D001393:Azoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase