Northeast Agricultural University, Harbin, 150030, PR China.
Heilongjiang Academy of Agricultural Sciences, Harbin, 150086, PR China.
Fish Shellfish Immunol. 2023 Nov;142:109100. doi: 10.1016/j.fsi.2023.109100. Epub 2023 Oct 2.
Tetrabromobisphenol A (TBBPA) and lead (Pb) are widely used in industrial field, which poses a serious threat to human and animal health. In particular, a large volume of wastewater containing TBBPA and Pb was discharged into the aquatic environment, causing a seriously negative impact on fish. Currently, whether TBBPA and Pb have a synergistic toxicity on fish remains unclear. In this study, we used the grass carp hepatocytes (L8824 cell line) exposed to either TBBPA or Pb, or both to determine their potential impacts on fish. The results showed that Pb or TBBPA induced oxidative stress and the loss of mitochondrial membrane potential in grass carp hepatocytes. In contrast to the control cells, the levels of JAK2, p-JAK2, STAT3 and p-STAT3 were significantly upregulated after exposure to TBBPA and Pb. Furthermore, the levels of Caspase3, Caspase9 and Bax were all increased while the level of Bcl2 was decreased in hepatocytes exposed to TBBPA or Pb. Results of flow cytometry and AO/EB staining reveled significant increases in the number of apoptotic cells in the TBBPA and Pb group compared to the controls. Notably, cells exposed to both TBBPA and Pb exhibited more severe damage than the single exposure, manifested by a higher number of apoptotic cells in the co-exposure group than the single exposure groups. Nevertheless, N-acetyl-l-cysteine (NAC) treatment could remarkably alleviate oxidative damage and loss of membrane potential in grass carp hepatocytes induced by TBBPA and Pb. Altogether, our study showed that combined exposure of TBBPA and Pb has a synergistic toxicity due to, inducing oxidative stress to activate JAK2/STAT3 signaling pathway, resulting in apoptosis of carp hepatocytes. This study shed a new light on the toxicological mechanism of exposure of TBBPA and Pb and provided a potential treatment of toxicity induced by TBBPA and Pb.
四溴双酚 A（TBBPA）和铅（Pb）广泛应用于工业领域，对人类和动物健康构成严重威胁。特别是含有 TBBPA 和 Pb 的大量废水被排放到水环 境中，对鱼类造成了严重的负面影响。目前，TBBPA 和 Pb 是否对鱼类具有协同毒性尚不清楚。在本研究中，我们使用草鱼肝细胞（L8824 细胞系）暴露于 TBBPA 或 Pb 或两者，以确定它们对鱼类的潜在影响。结果表明，Pb 或 TBBPA 诱导草鱼肝细胞氧化应激和线粒体膜电位丧失。与对照细胞相比，暴露于 TBBPA 和 Pb 后，JAK2、p-JAK2、STAT3 和 p-STAT3 的水平明显上调。此外，暴露于 TBBPA 或 Pb 的肝细胞中 Caspase3、Caspase9 和 Bax 的水平均升高，而 Bcl2 的水平降低。流式细胞术和 AO/EB 染色的结果表明，与对照组相比，TBBPA 和 Pb 组的凋亡细胞数量明显增加。值得注意的是，与单独暴露相比，同时暴露于 TBBPA 和 Pb 的细胞表现出更严重的损伤，表现为共暴露组的凋亡细胞数量高于单独暴露组。然而，N-乙酰-L-半胱氨酸（NAC）处理可显著减轻 TBBPA 和 Pb 诱导的草鱼肝细胞氧化损伤和膜电位丧失。总之，我们的研究表明，TBBPA 和 Pb 的联合暴露具有协同毒性，因为它会诱导氧化应激激活 JAK2/STAT3 信号通路，导致鲤鱼肝细胞凋亡。这项研究为 TBBPA 和 Pb 暴露的毒理学机制提供了新的见解，并为 TBBPA 和 Pb 诱导的毒性提供了一种潜在的治疗方法。
