Qian Man, Geng Yuan, Wang Jing-Jing, Wang Hong-Ru, Luo Ji-Long, Gao Xue-Jiao
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
Aquat Toxicol. 2025 Feb;279:107190. doi: 10.1016/j.aquatox.2024.107190. Epub 2024 Dec 1.
Tetrabromobisphenol A (TBBPA) is an aquatic environment's prevalent pollutant, posing a great threat to the health of aquatic animals. The intestine is a key organ for nutrient absorption as well as an important barrier to prevent pollutants from invading the body of fish. Exploring the effects of pollutants on the intestine is of great significance for maintaining fish health. Therefore, the purpose of this study was to assess the toxic effects of TBBPA on the intestine of Cyprinus carpio L. (common carp) by establishing models of common carp and primary intestinal epithelial cells exposed to TBBPA. Histological observation revealed that TBBPA exposure led to damage in the intestinal mucosa and breakage of intestinal villi. Detection of oxidative stress levels showed that TBBPA increased the levels of ROS and MDA, and decreased the activity of SOD, CAT, GSH-PX, and T-AOC in intestinal tissue and cells. Observation of inflammatory factor levels revealed that TBBPA upregulated the mRNA levels of inflammatory factors (IL-6, TNF-α, IL-1β, NF-κB p65 and IκBα). ELISA and western blotting results were consistent with the mRNA results. Moreover, TBBPA induced cell death, as evidenced by TUNEL staining and flow cytometry and confirmed by increasing levels of Bax, Cas-3, Cyt C, RIP1, RIP3, and MLKL, together with decreasing the levels of Bcl-2. TBBPA also destroyed the intestinal tight junction by reducing the mRNA and protein levels of claudin-1, ZO-1, and occludin. In summary, this study reveals that TBBPA caused intestinal injuries, inducing oxidative stress, inflammation, cell death, and tight junction disruption via ROS/NF-κB signal in common carp.
四溴双酚A（TBBPA）是一种在水生环境中普遍存在的污染物，对水生动物的健康构成了巨大威胁。肠道是营养物质吸收的关键器官，也是防止污染物侵入鱼体的重要屏障。探究污染物对肠道的影响对于维持鱼类健康具有重要意义。因此，本研究的目的是通过建立暴露于TBBPA的鲤鱼和原代肠上皮细胞模型，评估TBBPA对鲤（鲤鱼）肠道的毒性作用。组织学观察显示，TBBPA暴露导致肠道黏膜损伤和肠绒毛断裂。氧化应激水平检测表明，TBBPA增加了肠道组织和细胞中活性氧（ROS）和丙二醛（MDA）的水平，并降低了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-PX）和总抗氧化能力（T-AOC）的活性。炎症因子水平观察显示，TBBPA上调了炎症因子（白细胞介素-6、肿瘤坏死因子-α、白细胞介素-1β、核因子-κB p65和IκBα）的mRNA水平。酶联免疫吸附测定（ELISA）和蛋白质印迹法结果与mRNA结果一致。此外，TBBPA诱导细胞死亡，这通过末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色和流式细胞术得到证实，并通过增加Bax、半胱天冬酶-3（Cas-3）、细胞色素C（Cyt C）、受体相互作用蛋白1（RIP1）、受体相互作用蛋白3（RIP3）和混合谱系激酶结构域样蛋白（MLKL）的水平以及降低Bcl-2的水平得到进一步确认。TBBPA还通过降低闭合蛋白-1（claudin-1）、紧密连接蛋白1（ZO-1）和闭合蛋白（occludin）的mRNA和蛋白质水平破坏了肠道紧密连接。综上所述，本研究表明，TBBPA通过ROS/核因子-κB信号通路导致鲤鱼肠道损伤，诱导氧化应激、炎症、细胞死亡和紧密连接破坏。
