Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Environ Pollut. 2022 Aug 1;306:119421. doi: 10.1016/j.envpol.2022.119421. Epub 2022 May 6.
Graphene oxide (GO) has been widely studied and applied in numerous industrial fields and biomedical fields for its excellent physical and chemical properties. Along with the production and applications of GO persist increasing, the environmental health and safety risk (EHS) of GO has been widely studied. However, previous studies almost focused on the biotoxicity of pristine GO under a relatively high exposure dose, without considering its transformation process within environmental and biological mediums. Meanwhile, its secondary toxicity or synergistic effects have not been taken seriously. Here, two different kinds of artificial lung fluids were adopted to incubate pristine GO to mimic the biotransformation process of GO in the lung fluids. And, we explored that biotransformation within the artificial lung fluids could significantly change the physicochemical properties of GO and could enhance its biotoxicity. To reveal the synergistic effects of GO and toxic metal ions, we uncovered that GO could enhance the intracellular content of metal ions by inhibiting the efflux function of ATP binding cassette (ABC) transporters which are distributed on the cellular membrane, and artificial lung fluids incubation of GO could enhance this synergistic effect. Finally, toxic metal ions induced a series of toxic reactions through oxidative stress response and promoted cell death. Moreover, consistent with the results of in vitro experiments, the lungs of mice exposed to GOs combined with Cd exhibited significant inflammation and oxidative stress compared with Cd treatment alone, and it was more remarkable within the mice which were treated with bio-transformed GOs. In summary, this study explored the impact and mechanism of biotransformation of GO in the lung fluids on the synergistic and secondary effects between GO and metal ions.
氧化石墨烯（GO）因其优异的物理化学性能而被广泛应用于众多工业领域和生物医学领域。随着 GO 的生产和应用的不断增加，GO 的环境健康和安全风险（EHS）已得到广泛研究。然而，以前的研究几乎都集中在高暴露剂量下原始 GO 的生物毒性上，而没有考虑其在环境和生物介质中的转化过程。同时，其二次毒性或协同效应也没有得到重视。在这里，我们采用了两种不同的人工肺液来孵育原始 GO，以模拟 GO 在肺液中的生物转化过程。并且，我们发现生物转化可以显著改变 GO 的物理化学性质，并增强其生物毒性。为了揭示 GO 和有毒金属离子的协同效应，我们发现 GO 可以通过抑制分布在细胞膜上的三磷酸腺苷结合盒（ABC）转运蛋白的外排功能来增强金属离子的细胞内含量，而人工肺液孵育 GO 可以增强这种协同效应。最后，有毒金属离子通过氧化应激反应引发一系列毒性反应，并促进细胞死亡。此外，与体外实验结果一致，与单独 Cd 处理相比，暴露于同时含有 GOs 和 Cd 的小鼠肺部表现出明显的炎症和氧化应激，而在接受生物转化 GOs 处理的小鼠中更为明显。综上所述，本研究探讨了 GO 在肺液中的生物转化对 GO 与金属离子之间协同和二次效应的影响和机制。
