Dysmorphogenic effects of some fungicides derived from the imidazole on rat embryos cultured in vitro.
Like triazole-derivatives, imidazole-derivatives exert their antifungal and toxicological properties by inhibiting P450 enzymes (Cyps). At the embryonic level, Cyp enzymes are involved also in the catabolism of the retinoic acid. Specific effects of triazole-derivatives have been reported on developing rodent embryos, and were correlated to an imbalance of the retinoid homeostasis. The aim of this work was to investigate if imidazole-derivatives are able to induce specific malformations similar to those observed after triazole-derivative exposure. Post implantation rat embryos were exposed in vitro to 1,000 microM Imidazole and to 5-100 microM of the imidazole-derivatives Ketoconazole and Enilconazole. After 48 h in culture, the embryos exposed to the imidazole-derivatives showed specific malformations, quite similar to those observed after triazole-derivative exposure. The common dysmorphogenic effects of the azole-derivatives of the two classes could be due to the inhibition of retinoid catabolism. From this point of view, the contemporaneous exposure to these substances or their therapeutic use could be considered as potentially dangerous for human conceptuses.
Menegola
Elena
E
Department of Biology, University of Milan, Via Celoria 26, 20133 Milan, Italy. elena.menegola@unimi.it
Broccia
Maria L
ML
Di Renzo
Francesca
F
Giavini
Erminio
E
D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D047108:Embryonic Development / Q000187:drug effects*; D005659:Fungicides, Industrial / Q000633:toxicity; D007093:Imidazoles / Q000633:toxicity*; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens / Q000633:toxicity
D000935:Antifungal Agents; D005659:Fungicides, Industrial; D007093:Imidazoles; D013723:Teratogens; C017435:enilconazole; C029899:imidazole; D007654:Ketoconazole