Postulated pathogenic pathway in triazole fungicide induced dysmorphogenic effects.
Triazole fungicides are used in medicine as well as in agricultural treatment of mycoses. The pharmacological mechanism is related to the inhibition of CYP enzymes involved in the formation of the fungal walls. A similar inhibition of human CYP enzymes has been suggested as the cause of triazole side effects in humans. An important role of some CYP isoforms (CYP26 isoforms) expressed during mammalian development is the catabolism of retinoic acid, a known morphogen in vertebrates and invertebrates. The adverse effects on morphogenesis, observed after exposure of mammalian, amphibian and ascidiacea, are compared to the reported effects of triazole in humans. The possible pathogenic pathway in triazole-related teratogenesis is discussed on the basis of different experimental approaches.
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; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000633:toxicity; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D013723:Teratogens / Q000633:toxicity; D014212:Tretinoin / Q000378:metabolism; D014230:Triazoles / Q000633:toxicity*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005659:Fungicides, Industrial; D013723:Teratogens; D014230:Triazoles; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System