Mitigation of arsenic induced developmental cardiotoxicity by ferulic acid in zebrafish

Abstract

We investigated whether ferulic acid (FA), a nutraceutical could mitigate the arsenic (As) induced cardiotoxicity. Zebrafish larvae (60 and 72 h post-fertilization [hpf]) were used to study the effect of FA on As at different time points (24 and 48 h after exposure). The FA exposure was given as pre-treatment (60 hpf) and simultaneous treatment (72 hpf) to translate the results for As contaminated areas. To accomplish this, the lethality assay was done, and based on the results, the dosage for As (1 mM) and FA (30 μM) was fixed. The FA intervention (30 μM) as 12 h pre-treatment (60 hpf) and simultaneous treatment along with As (72 hpf) decreased the As content in zebrafish larvae as evidenced by inductively coupled plasma-mass spectrometry. As exposure showed congenital deformities especially cardiac malformations in zebrafish larvae after 24 and 48 h. These teratogenic effects induced by As were reduced by FA supplementation in both groups. Also, o-dianisidine staining demonstrated that As treated larvae encountered abnormal cardiac function with reduced blood circulation, while FA supplementation reversed these effects. The acetylcholinesterase activity, a biomarker of As-induced cardiotoxicity was also found to be decreased in As group, which was rescued by FA. The modulation in the expression of the genes involved in cardiogenesis (nkx2.5, bmp2b, gata4, gata5, myh6, myl7, and tnnt2) further confirmed the ameliorative effect of FA on As induced malformations.