Di-(2-ethyl hexyl)phthalate (DEHP) is a kind of plasticizer that can cause cardiovascular disorders in animals, but its specific mechanism of action has not been determined. We aimed to investigate whether taxifolin (TAX) can antagonize the cytotoxicity of DEHP on cardiomyocytes. Chicken cardiomyocytes were treated with DEHP (500 μM) and/or TAX (0.5 μM) for 24 h. Ca2+ staining showed that the concentration of Ca2+ in the cytoplasm of cardiomyocytes was significantly increased under DEHP stimulation. However, in the DEHP + TAX group, the Ca2+ concentration was largely restored. In addition, the results of necroptosis--fluorescent and flow cytometry analysis showed that the DEHP group had severe necroptosis compared with the control group. The necrotic rate in the DEHP + TAX group was significantly lower than that in the DEHP group. At the mRNA and protein levels, the expression of the necrotic-calcium pathway genes RIPK1, RIPK3, MLKL, FAS, Caspase-8, CAMKII, and SERCA in the DEHP group increased to varying degrees relative to the control group. However, TAX improved this injury. Compared with the DEHP group, the expression of these genes was significantly decreased in the DEHP + TAX group. The present study indicate that DEHP could trigger cardiomyocyte necroptosis through Ca2+ overload, which could be alleviated by TAX.
Keywords: Calcium; Cardiomyocytes; Di-(2-ethyl hexyl)phthalate; Necroptosis; Taxifolin.
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