Embryonic protective role of folate in arsenic-induced cardiac malformations in rats

作者：Lin, Yuan^*; Zhuang, Lingzi; Yi, Huan; Xu, Liangpu; Huang, Hailong; He, Deqin; Zhao, Xiumei; Ma, Hong; Wu, Lixiang

来源：International Journal of Clinical and Experimental Pathology, 2018, 11(4): 1946-1955.

• Arsenic
• folate
• congenital heart disease
• Nkx2.5
• GATA-4
• TBX5

Background: To investigate impacts of sodium arsenic (NaAsO2) on embryonic cardiac development in rats and evaluate the protective role of folate in NaAsO2 exposure rats. Methods: We divided 90 female rats randomly into 9 groups. Group A was the control; group B-F were the animals fed with NaAsO2 in a series of increased doses, corresponding to 9.4 mg/L, 18.8 mg/L, 37.5 mg/L, 75 mg/L and 150 mg/L, respectively; group G-I were fed with 75 mg/L of NaAsO2, in addition of folate with doses of 0.53 mg/kg, 5.3 mg/kg, and 10.6 mg/kg, respectively. Their fetus' general development and cardiovascular systems were examined. Nkx2.5, GATA4, TBX5 gene and protein expression were measured. Results: Relatively to group A, arsenic treated group C-F rats generated significantly lower weight of fetus and placenta (P<0.05), whereas the folate-treated groups H and I were significantly heavier than the arsenic-treated group E (P<0.05). We observed that incidences of cardiac malformations were significantly greater in arsenic-treated group E and F than group A (P<0.05). We found that the Nkx2.5 and GATA4 protein expression in the fetal hearts were downregulated in group B-F compared to group A. But the expression of them was significantly upregulated in group H-I relatively to group E (P<0.05). Moreover, the TBX5 gene expression was increased in both group D-F and G-I when they were compared to group A or group E, respectively (P<0.05). Conclusion: NaAsO2 induce embryonic cardiac defection and folate supplement alleviate this impairment through modulation of the Nkx2.5, GATA4 and TBX5 gene expression.

• 出版日期2018
• 单位福建医科大学; 福建省妇幼保健院