Taxifolin alleviates apoptotic injury induced by DEHP exposure through cytochrome P450 homeostasis in chicken cardiomyocytes.

Di-2-ethylhexyl phthalate (DEHP), widely used as a plasticizer, is a ubiquitous artificial pollutant. DEHP can induce biological toxicity in various organs, with an especially high potential for toxicity to the cardiovascular system. Taxifolin (TAX) is used in the treatment of cardiovascular diseases due to its antioxidative capacities. However, it is not clear whether TAX can alleviate apoptosis induced by DEHP exposure through the cytochrome P450 (CYP) pathway in cardiomyocytes. To understand the role of TAX in attenuating cardiomyocyte toxicity induced by DEHP, primary cardiomyocytes were divided into 4 groups (control group, DEHP group, TAX group and DEHP + TAX group). The results showed that in the cardiomyocytes, DEHP initiated apoptosis by increasing the expression of caspase-3, caspase-9, cyt c, and Bax at both the mRNA and protein levels and by decreasing the Bcl-2 levels compared with that of the control group. In addition, the activities of catalase (CAT), superoxide dismutase (SOD), and total antioxidative capacity (T-AOC) were clearly decreased (P < 0.05), while in the DEHP group, the malondialdehyde (MDA) and hydrogen peroxide (HO) levels were observably increased (P < 0.05), compared with those in control group. Furthermore, compared with the control group, the DEHP group demonstrated a clear partial decrease in the expression of the mRNA levels of CYP1B1 and CYP2C18 (P < 0.05), and DEHP/TAX cotreatment partially prevented apoptosis and oxidative stress damage (P < 0.05). These results showed that exposure to DEHP induced apoptosis in chicken cardiomyocytes, while TAX could antagonize the toxicity of DEHP on cardiomyocytes by attenuating oxidative stress responses and modulating CYPs.