College of Life Science, Henan Normal University, Xinxiang, Henan, 453007, China.
College of Life Science, Henan Normal University, Xinxiang, Henan, 453007, China.
Environ Pollut. 2018 Nov;242(Pt B):1337-1345. doi: 10.1016/j.envpol.2018.08.003. Epub 2018 Aug 11.
Ionic liquids (ILs) as a green replacement for volatile organic solvents are increasingly used in large-scale commercial applications. A good understanding of the toxic mechanisms and environmental impact of ILs is neede to reduce the risk for human health and the environment. For this purpose, we aimed to evaluate the possible impacts of 1-methyl-3-octylimidazolium bromide ([Cmim]Br) exposure on human hepatocellular carcinoma (HepG2) cells as to elucidate the cytotoxic mechanism of [Cmim]Br. Biochemical assays revealed that [Cmim]Br exposure altered the protein levels of heat shock protein 70 (HSP70) and HSP90, generally inhibiting total antioxidative capacity (T-AOC), depleting heme oxygenase-1 (HO-1) and increasing transcription and activity of inducible nitric oxide synthase (iNOS) in HepG2 cells. These results indicated that [Cmim]Br may induce biochemical disturbances and cause oxidative stress in HepG2 cells. Moreover, increased phosphorylation of p53, mitochondrial membrane disruption, cyclooxygenase-2 activation, Bcl-2 family protein modulation, cytochrome c and Smac/DIABLO release, and inhibition of apoptosis inhibitory protein-2 (c-IAP2) and survivin were also observed in [Cmim]Br-treated cells, suggesting that [Cmim]Br-induced apoptosis might be mediated by the mitochondrial pathway. Further research showed that [Cmim]Br exposure increased tumour necrosis factor α (TNF-α) transcription and content and promoted the expression of Fas and FasL, indicating that TNF-α and Fas/FasL are involved in the apoptosis induced by [Cmim]Br. Additionally, [Cmim]Br cytotoxicity was partly inhibited by N-acetyl-cysteine (NAC), and NAC reversed [Cmim]Br-mediated mitochondrial dysfunction and blocked apoptotic events by inhibiting the generation of reactive oxygen species (ROS). This work first demonstrated that the ROS-mediated mitochondrial and death receptor-initiated apoptotic pathway is involved in [Cmim]Br-induced HepG2 cell apoptosis.
离子液体（ILs）作为挥发性有机溶剂的绿色替代品，越来越多地被应用于大规模商业应用。为了降低对人类健康和环境的风险，需要更好地了解 ILs 的毒性机制和环境影响。为此，我们旨在评估 1-甲基-3-辛基咪唑溴 ([Cmim]Br) 暴露对人肝癌细胞（HepG2）的可能影响，以阐明 [Cmim]Br 的细胞毒性机制。生化测定表明，[Cmim]Br 暴露改变了热休克蛋白 70（HSP70）和 HSP90 的蛋白水平，普遍抑制总抗氧化能力（T-AOC），耗竭血红素加氧酶-1（HO-1），并增加诱导型一氧化氮合酶（iNOS）在 HepG2 细胞中的转录和活性。这些结果表明，[Cmim]Br 可能在 HepG2 细胞中诱导生化紊乱并引起氧化应激。此外，还观察到 p53 磷酸化增加、线粒体膜破坏、环氧化酶-2 激活、Bcl-2 家族蛋白调节、细胞色素 c 和 Smac/DIABLO 释放，以及凋亡抑制蛋白-2（c-IAP2）和 survivin 的抑制，表明 [Cmim]Br 诱导的细胞凋亡可能是通过线粒体途径介导的。进一步的研究表明，[Cmim]Br 暴露增加了肿瘤坏死因子 α（TNF-α）的转录和含量，并促进了 Fas 和 FasL 的表达，表明 TNF-α 和 Fas/FasL 参与了 [Cmim]Br 诱导的细胞凋亡。此外，[Cmim]Br 的细胞毒性部分被 N-乙酰半胱氨酸（NAC）抑制，NAC 通过抑制活性氧（ROS）的产生逆转了 [Cmim]Br 介导的线粒体功能障碍并阻断了凋亡事件。这项工作首次表明，ROS 介导的线粒体和死亡受体起始的凋亡途径参与了 [Cmim]Br 诱导的 HepG2 细胞凋亡。
