Quercetin antagonizes apoptosis, autophagy and immune dysfunction induced by di(2-ethylhexyl) phthalate via ROS/ASK1/JNK pathway

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Comparative Biochemistry and Physiology C-toxicology & Pharmacology Pub Date : 2024-08-03 DOI:10.1016/j.cbpc.2024.109991
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Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that can damage various organizations and physiques through oxidative stress. Quercetin (Que) is a rich polyphenol flavonoid with good anti-inflammatory and antioxidant effects. However, the protection mechanism of Que against DEHP exposure-induced IPEC-J2 cell injury and the implication of autophagy, apoptosis and immunity are still unclear. In this experiment, we looked into the toxicity regime of DEHP exposure on IPEC-J2 cells and the antagonistic function of Que on DEHP. In the experiment, 135 μM DEHP and/or 80 μM Que were used to treat the IPEC-J2 cells for 24h. Experiments indicated that DEHP exposure can cause increased reactive oxygen species (ROS) levels leading to oxidative stress, decreased CAT, T-AOC and GSH-Px activities, increased MDA and H2O2 accumulation, activated the ASK1/JNK signalling pathway, and further increases in the levels of apoptosis markers Bax, Caspase3, Caspase9, and Cyt-c, while reduced the Bcl-2 expression. DEHP also increased the expression of genes linked to autophagy (ATG5, Beclin1, LC3), while decreasing the expression of P62. Additionally, DEHP exposure led to elevated levels of IL1-β, IL-6, MCP-1, and TNF expression. When exposed to Que alone, there were no significant changes in cellular oxidative stress level, ASK1/JNK signalling pathway expression level, apoptosis, autophagy and cellular immune function. The combination of DEHP and Que treatment remarkably decreased the proportion of autophagy and apoptosis, and recovered cellular immunity. In summary, Que can attenuate DEHP-induced apoptosis and autophagy in IPEC-J2 cells by regulating the ROS/ASK1/JNK signalling pathway and improving the immune dysfunction of IPEC-J2 cells.

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槲皮素可通过 ROS/ASK1/JNK 通路拮抗邻苯二甲酸二(2-乙基己基)酯诱导的细胞凋亡、自噬和免疫功能紊乱。
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种增塑剂,可通过氧化应激损害各种组织和身体。槲皮素(Que)是一种丰富的多酚类黄酮,具有良好的抗炎和抗氧化作用。然而,槲皮素对DEHP暴露诱导的IPEC-J2细胞损伤的保护机制以及自噬、细胞凋亡和免疫的影响尚不清楚。在本实验中,我们研究了 DEHP 暴露对 IPEC-J2 细胞的毒性机制以及 Que 对 DEHP 的拮抗作用。实验中,使用 135 μM DEHP 和/或 80 μM Que 处理 IPEC-J2 细胞 24 小时。实验表明,暴露于 DEHP 会导致活性氧(ROS)水平升高,导致氧化应激,降低 CAT、T-AOC 和 GSH-Px 活性,增加 MDA 和 H2O2 的积累,激活 ASK1/JNK 信号通路,进一步提高细胞凋亡标志物 Bax、Caspase3、Caspase9 和 Cyt-c 的水平,同时降低 Bcl-2 的表达。DEHP 还增加了与自噬相关的基因(ATG5、Beclin1、LC3)的表达,同时降低了 P62 的表达。此外,暴露于 DEHP 会导致 IL1-β、IL-6、MCP-1 和 TNF 表达水平升高。单独暴露于 Que 时,细胞氧化应激水平、ASK1/JNK 信号通路表达水平、细胞凋亡、自噬和细胞免疫功能均无明显变化。DEHP和Que联合处理可显著降低自噬和细胞凋亡的比例,恢复细胞免疫功能。综上所述,Que能通过调节ROS/ASK1/JNK信号通路减轻DEHP诱导的IPEC-J2细胞凋亡和自噬,改善IPEC-J2细胞的免疫功能障碍。
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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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