Taxifolin alleviates apoptotic injury induced by DEHP exposure through cytochrome P450 homeostasis in chicken cardiomyocytes
Taxifolin alleviates apoptotic injury induced by DEHP exposure through cytochrome P450 homeostasis in chicken cardiomyocytes
复制标题
紫杉叶素通过细胞色素 P450 稳态减轻鸡心肌细胞 DEHP 诱导的细胞凋亡损伤
DOI：
10.1016/j.ecoenv.2019.109582
复制
发表时间：
2019
影响因子：
6.8
通讯作者：
Zhang Ziwei
中科院分区：
文献类型：
--
作者：
Zhang Yuan;Shi Guangliang;Cai Jingzeng;Yang Jie;Zheng Yingying;Yu Dahai;Liu Qi;Gong Yafan;Zhang Ziwei
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种普遍存在的人工污染物，广泛用作增塑剂. DEHP可在各种器官中诱导生物毒性，尤其是对心血管系统的潜在毒性。Taxifolin（TAX）由于其抗氧化能力而用于治疗心血管疾病。然而，尚不清楚TAX是否可以通过心肌细胞中的细胞色素P450（CYP）途径减轻DEHP暴露诱导的细胞凋亡。为了解TAX在减轻DEHP诱导的心肌细胞毒性中的作用，将原代心肌细胞分为4组（对照组、DEHP组、TAX组和DEHP + TAX组）。结果表明，DEHP通过增加caspase-3、caspase-9、cyt c和Bax在mRNA和蛋白水平的表达，降低Bcl-2水平，诱导心肌细胞凋亡。与对照组相比，DEHP组过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和总抗氧化能力（T-AOC）明显降低（P < 0.05），丙二醛（MDA）和过氧化氢（H2 O2）水平明显升高（P < 0.05）。与对照组相比，DEHP组细胞CYP 1B 1和CYP 2C 18 mRNA表达水平明显降低（P < 0.05），DEHP/TAX联合处理可部分抑制细胞凋亡和氧化应激损伤（P < 0.05）。以上结果表明，DEHP可诱导鸡心肌细胞凋亡，而TAX可通过减轻心肌细胞氧化应激反应和调节CYP活性来拮抗DEHP对心肌细胞的毒性作用。
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 (H2O2) 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.