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TBBPA and lead co-exposure induces grass carp liver cells apoptosis via ROS/JAK2/STAT3 signaling axis

四溴双酚A 细胞凋亡 氧化应激 草鱼 活性氧 流式细胞术 生物 毒性 分子生物学 化学 内科学 内分泌学 生物化学 渔业 医学 有机化学 阻燃剂
作者
Lu Li,Li Wan,Yufeng Liu,Xin Jin,Yanbo Yu,Hongjin Lin
出处
期刊:Fish & Shellfish Immunology [Elsevier BV]
卷期号:142: 109100-109100 被引量:16
标识
DOI:10.1016/j.fsi.2023.109100
摘要

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.
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