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Fig. 2 Characterization of the combined LAP and DOX exposure-induced cardiotoxicity phenotype in zebrafish embryos. (A) Representative fluorescence images of embryonic hearts immune-stained with the anti-α-actinin antibody in the combined LAP and DOX exposure-induced cardiotoxicity model and the DMSO control. A, atrium; V, ventricle. (B) Representative fluorescence images of embryonic hearts in the Tg(cmlc2:DsRed) transgenic fish after combined LAP and DOX exposure compared to the DMSO control at 72 hpf. (C) Representative images outlining cross-sectional area of cardiomyocytes by immunostaining with anti–β-catenin (red) and anti–myocyte enhancer factor-2 (Mef2, green) antibodies in the LAP and DOX combination-induced cardiotoxicity model and DMSO control at 72 hpf. (D) Representative fluorescence images of TUNEL-stained embryonic hearts in the LAP and DOX combination-induced cardiotoxicity model and DMSO control. (E) Upper panels, shown are Masson’s trichrome stain images to detect fibrosis from the heart chambers of LAP and DOX treated embryos compared to DMSO control at 72 hpf. Lower panels, transmission electron microscopy (TEM) images confirmed the disruption of sarcomere structure and empty mitochondrial defects in the combined LAP and DOX exposure-induced cardiotoxicity model. The arrow indicates degenerative sarcomeres. The asterisks point to empty mitochondrial defects. (F-H) Quantification of cardiomyocyte numbers (F), cardiomyocyte cross-section area (G) and the TUNEL index (H) in the LAP and DOX combination-induced cardiotoxicity model and DMSO control at 72 hpf. N=4–5, Student’s t test. *P<0.05，**P<0.01. A, atrium; V, ventricle.