title: Pyridoxine might not have a preventive effect on the retinyl palmitate-induced viscerocranial anomalies.
abstract: Viscerocranial anomalies are induced in the presence of various teratogens. Vitamin A-induced cleft palate formation is one of the most frequently used experimental models in these studies. However, the underlying mechanisms are not yet fully understood. Several studies have shown that exogenous vitamin A disrupts the fusion of the palatal shelves by increasing the expression of epidermal growth factor receptor (EGFR). More recently, pyridoxine (vitamin B6) has been reported to have a potentially protective effect in regard to viscerocranial malformations. Therefore, in this study, we aimed to investigate whether pyridoxine has a preventive effect on retinyl palmitate-induced viscerocranial anomalies. The frequency of gross malformations induced by retinyl palmitate, the natural form of vitamin A, has been studied in a dose dependent manner. Low doses of retinyl palmitate (100 mg/kg) exposure on embryonic day (ED) 10 caused no gross anomalies in the rat fetuses. Teratogenic effects were observed only after exposure to higher dosages (1000 mg/kg) and primarily targeted the developing eyes and palates. On the other hand, co-administration of 10mg/kg pyridoxine, at ED 9 and 10, significantly increased the frequencies of anomalies, even in the moderate dosage (500 mg/kg) group. In all cleft palates, sustained expression of EGFR in the medial edge epithelium was detected by immunohistochemistry. These results show that co-administration of pyridoxine has an inductive rather than protective effect on the formation of viscerocranial malformations after exposure to hypervitaminosis-A.
authors.affiliation: Department of Anatomy, Faculty of Medicine, Eskişehir Osmangazi University, 26480 Eskişehir, Turkey. hakanay@ogu.edu.tr
authors.forename: Hakan
authors.initials: H
authors.lastname: Ay
authors.forename: Emel
authors.initials: E
authors.lastname: Ulupinar
authors.forename: Nedim
authors.initials: N
authors.lastname: Unal
mesh_terms: D000818:Animals; D001921:Brain / Q000002:abnormalities*; D002585:Cesarean Section; D019465:Craniofacial Abnormalities / Q000139:chemically induced* / Q000196:embryology / Q000517:prevention & control; D004065:Digestive System Abnormalities / Q000139:chemically induced* / Q000196:embryology / Q000517:prevention & control; D004224:Diterpenes; D005124:Eye Abnormalities / Q000139:chemically induced / Q000196:embryology / Q000517:prevention & control; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D011247:Pregnancy; D011736:Pyridoxine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000084562:Retinyl Esters; D013723:Teratogens / Q000633:toxicity; D014781:Viscera / Q000002:abnormalities* / Q000187:drug effects; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D004224:Diterpenes; D000084562:Retinyl Esters; D013723:Teratogens; D014801:Vitamin A; C014794:retinol palmitate; D011736:Pyridoxine