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. 2018 Apr 1;11(4):1946-1955.
eCollection 2018.

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

Affiliations

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

Yuan Lin et al. Int J Clin Exp Pathol. .

Abstract

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.

Keywords: Arsenic; GATA-4; Nkx2.5; TBX5; congenital heart disease; folate.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Effects of NaAsO2 exposure on embryonic heart development during Pregestation/gestation. ×40. A: Normal heart; B-D: ↑VSD; E: ↑ASD; F: ↑ASD; G: ↑Thin ventricular wall; H: Large atrial cavity; I, J: ↑Pulmonary stenosis. LV: left ventricular; RV: right ventricular; LA: left atrium; RA: right atrium; IVS: interventricular septum; IAS: interatrial septum; MV: mitral valve; TV: tricuspid valve; Ao: aorta; AoV: aortic valve; LVOT: left ventricular outflow tract; PA: pulmonary arterial; ↑: anomalous structure.
Figure 2
Figure 2
PCR amplification curve (left) and dissolution curve (right).
Figure 3
Figure 3
Relative mRNA levels of Nkx2.5, GATA4, TBX5 in each group’s embryonic heart. (▲Compared with group A, P>0.05; *Compared with group A, P<0.05; #Compared with group E, P>0.05; ΔCompared with group E, P<0.05).
Figure 4
Figure 4
Relative protein levels of Nkx2.5, GATA4 and TBX5 in embryonic heart of each group. (▲Compared with group A, P>0.05; *Compared with group A, P<0.05; #Compared with group E, P>0.05; ΔCompared with group E, P<0.05).
Figure 5
Figure 5
Results of Western Blot.

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