Comparative Study of Folic Acid and alpha-Naphthoflavone on Reducing TCDD-Induced Cleft Palate in Fetal Mice.

OBJECTIVE: Tocompare the effect of folic acid (FA) and alpha-naphthoflavone on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate in fetal mice. DESIGN: Pregnant mice were randomly divided into seven groups. The mice treated with corn oil were used as a negative control. The mice in the other six groups were given a single dose of 28 mug/kg TCDD on GD 10 by gavage. For FA treatment, TCDD-treated mice were also dosed with 5, 10, and 15 mg/kg FA on GD 10, while for alpha-naphthoflavone treatment, the mice received a single dose of 50 mug/kg or 5 mg/kg alpha-naphthoflavone on GD 10. MAIN OUTCOME MEASURES: Fetal mice palates were imaged using light and scanning electron microscopy on GD 13.5, GD 14.5, and GD 15.5, and cleft palate were recorded on GD 17.5. The expression of guanosine diphosphate dissociation inhibitor (GDI) in fetal mice palate on GD 15.5 was examined by immunohistochemistry. RESULTS: TCDD successfully induced cleft palate. Ten mg/ml FA and 5 mg/ml alpha-naphthoflavone significantly reduced TCDD-induced cleft palate. FA and alpha-naphthoflavone partly reduced TCDD-induced cleft palate but did not affect the expression of Rho GDI. CONCLUSIONS: FA and alpha-naphthoflavone may reduce the generation of reactive oxygen species, inhibit MEE apoptosis through anti-oxidation, and increase filopodia and MEE movement. This may result in restoration of the ultrastructure of the palatal surface to a normal state, leading to the fusion and formation of complete palate in TCDD-treated fetal mice.