Antagonistic effect of nano-selenium on hepatocyte apoptosis induced by DEHP via PI3K/AKT pathway in chicken liver
Antagonistic effect of nano-selenium on hepatocyte apoptosis induced by DEHP via PI3K/AKT pathway in chicken liver
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DOI：
10.1016/j.ecoenv.2021.112282
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发表时间：
2021-04-29
影响因子：
6.8
通讯作者：
Zhou, Donghai
中科院分区：
文献类型：
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作者：
Li, Hao;Zhang, Jiabin;Zhou, Donghai
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常用的增塑剂，主要用作塑料添加剂，以增加塑料制品的柔韧性。由于塑料制品的广泛使用，DEHP作为一种无所不在的人工污染物，广泛存在于环境中。此外，DEHP可通过氧化应激引起各器官的生物损伤。纳米硒是硒的一种新形式，作为抗氧化剂、抗癌剂和抗炎剂在生物医学上有着广泛的应用。然而，DEHP对鸡肝细胞系的毒性研究尚不充分。特别是在鸡细胞中对DEHP与纳米硒的相互作用研究不足。因此，本研究的创新之处在于探索DEHP对肝细胞毒性的理论机制，以及纳米硒对DEHP对鸡肝细胞一系列损伤的拮抗作用。我们的研究结果显示，DEHP暴露后，肝细胞氧化应激水平升高，凋亡相关基因p53、Capsase9、Caspase3和Bax mRNA和蛋白水平除Bcl-2外显著升高。凋亡标志物切割caspase9和切割caspase3的蛋白水平也显著升高。此外，TUNEL实验结果也显示DEHP暴露后凋亡细胞水平升高。同时，PI3K、AKT、p-AKT mRNA和蛋白水平降低。因此，DEHP能够增强鸡肝细胞的氧化损伤程度和凋亡程度。然而，纳米硒的加入可以逆转上述变化。实验结果表明，纳米硒通过PI3K/AKT通路拮抗DEHP的毒性作用。
Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer which is mainly used as a kind of plastic additive to increase the flexibility of plastic products. Given the widespread use of plastic products, DEHP, as a ubiquitous artificial pollutant, are widely present in the environment. In addition, DEHP could cause biological damage in various organs through oxidative stress. Nano-Selenium, a novel form of selenium, has a wide variety of biomedical applications as an antioxidant, anticancer and anti-inflammatory agent. Nevertheless, researches on the toxicity of DEHP in chicken hepatocyte lines is insufficient. In particular, researches on the interaction between DEHP and nano-selenium is insufficient in chicken cell. Therefore, the innovation of this study is to explore the theoretical mechanism of DEHP toxicity in hepatocytes and the antagonistic effect of nano-selenium on a series of damage in chicken hepatocytes caused by DEHP. Our results showed that, after DEHP exposure, oxidative stress levels in hepatocytes increased, and the mRNA and protein levels of apoptosis-related genes p53, Capsase9, Caspase3 and Bax increased significantly except Bcl-2. The protein levels of apoptosis markers cleavedCaspase9 and cleaved-Caspase3 also increased significantly. Moreover, the result of TUNEL assay also showed that the level of apoptotic cells increased after DEHP exposure. Meanwhile, the mRNA and protein levels of PI3K, AKT and p-AKT decreased. Therefore, DEHP is able to enhance the degree of oxidative damage and apoptosis of chicken liver cells. Nevertheless, the addition of nano-selenium can reverse the above changes. Experimental results revealed that nano-selenium antagonizes the toxic effects of DEHP via the PI3K/AKT pathway.