Fig. 1. Protective effects of FA or RSV at different concentrations on EOM-induced heart defects in zebrafish embryos at 72 hpf. (A, C) Representative images of zebrafish embryos; dotted lines encircle the atrium (red) or ventricle (blue). (B, D) Heart malformation rates. Different letters (a,b) indicate significant differences.

Fig. 2. RSV plus FA synergistically protected EOM-induced heart defects in zebrafish embryos at 72 hpf. (A) Representative images; dotted lines encircle the atrium (red) or ventricle (blue). (B) Heart malformation rate. (C) Survival rate. (D) Synergistic interaction analysis. Different letters (a,b) indicate significant differences.

Fig. 3. The effect of RSV, FA and RSV plus FA on EOM-induced AHR activity in the hearts of zebrafish embryos at 72 hpf. (A) EROD signals and the quantification results; the white dashed-line squares indicate heart area; (B) Synergistic interaction illustrated by interaction plots; (C) mRNA expression levels. Different letters (a,b) indicate significant differences.

Fig. 4. ROS signals in the hearts of zebrafish embryos at 72 hpf and the quantification results. (A) The effect of RSV, FA and RSV plus FA on EOM-induced ROS production; the white dashed-line squares indicate heart area; (B) The effect of FA at different concentrations. Different letters (a,b) indicate significant differences.

Fig. 5. The effect of RSV, FA and RSV plus FA on EOM-induced apoptosis in the hearts of zebrafish embryos at 72 hpf. (A) AO staining, the quantification results and synergistic interaction; (B) Cleaved caspase-3 staining of isolated hearts, the quantification results and synergistic interaction; (C) mRNA expression from isolated hearts. Different letters (a-c) indicate significant differences.

Fig. 6. Protective effects of VC at different concentrations or VC plus FA on EOM-induced heart defects in zebrafish embryos at 72 hpf. (A, B) Representative images of zebrafish embryos exposed to VC at different concentrations and heart malformation rates; dotted lines encircle atrium (red) or ventricle (blue). (C, D). Representative images of zebrafish embryos exposed to VC, FA and VC plus FA and the relevant heart malformation rates; E) Synergistic interaction illustrated by interaction plots; different letters (a,b) indicate significant differences.

Fig. 7. The effect of RSV, FA and RSV plus FA on EOM-induced AHR activity, ROS production and apoptosis in the hearts of zebrafish embryos at 72 hpf. (A) ROS production and the quantification result; the white dashed-line squares indicate heart area. (B) EROD signals for AHR activity and the quantification result. (C) AO staining, quantification result, and synergistic interaction; (D) Cleaved caspase-3 staining of isolated hearts, quantification result, and synergistic interaction; different letters (a-c) indicate significant differences.

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