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Zinc oxide/graphene oxide nanocomposites efficiently inhibited cadmium-induced hepatotoxicity via releasing Zn ions and up-regulating MRP1 expression
Environment International ( IF 10.3 ) Pub Date : 2022-06-01 , DOI: 10.1016/j.envint.2022.107327
Yun Liu 1 , Xue Wang 2 , Bo Si 1 , Tong Wang 1 , Yun Wu 3 , Ying Liu 1 , Yemian Zhou 1 , Haiyang Tong 3 , Xinwei Zheng 3 , An Xu 4
Affiliation  

Environmental cadmium (Cd) pollution has been verified to associated with various hepatic diseases, as Cd has been classified as one of the TOP 20 Hazardous Substances and liver is the main target of Cd poisoning. However, to design efficient hepatic antidotes with excellent detoxification capacity and reveal their underlying mechanism(s) are still challenges in Cd detoxification. Herein, ZnO/GO nanocomposites with favorable biocompatibility was uncovered their advanced function against Cd-elicited liver damage at the in situ level in vivo by 9.4 T magnetic resonance imaging (MRI). To explore the cellular detoxification mechanism, ZnO/GO nanocomposites was found to effectively inhibit the cyto- and geno-toxicity of Cd with the maximum antagonistic efficiency to be approximately 90%. Mechanistically, ZnO/GO nanocomposites competitively inhibited the cellular Cd uptake through releasing Zn ions, and significantly promoted Cd excretion via targeting the efflux pump of multidrug resistance associated protein1 (MRP1), which was confirmed by mass spectra and immunohistochemical analysis in kidney, a main excretion organ of Cd. Our data provided a novel approach against Cd-elicited hepatotoxic responses by constructed ZnO/GO nanocomposites both in vitro and in vivo, which may have promising application in prevention and detoxification for Cd poisoning.



中文翻译:

氧化锌/氧化石墨烯纳米复合材料通过释放锌离子和上调MRP1表达有效抑制镉诱导的肝毒性

环境镉(Cd)污染已被证实与多种肝脏疾病有关,因为镉被列为20大有害物质之一,肝脏是镉中毒的主要目标。然而,设计具有优异解毒能力的高效肝脏解毒剂并揭示其潜在机制仍然是镉解毒的挑战。在此,揭示了具有良好生物相容性的 ZnO/GO 纳米复合材料在体内原位水平上对抗镉引起的肝损伤的先进功能通过 9.4 T 磁共振成像 (MRI)。为了探索细胞解毒机制,发现 ZnO/GO 纳米复合材料可有效抑制 Cd 的细胞毒性和基因毒性,最大拮抗效率约为 90%。从机理上讲,ZnO/GO 纳米复合材料通过释放 Zn 离子竞争性抑制细胞对 Cd 的吸收,并通过靶向多药耐药相关蛋白 1 (MRP1) 的外排泵显着促进 Cd 的排泄,这一点已通过肾脏的质谱和免疫组织化学分析得到证实。镉的排泄器官。我们的数据提供了一种通过在体外体内构建的 ZnO/GO 纳米复合材料来对抗 Cd 引发的肝毒性反应的新方法, 在镉中毒的预防和解毒方面可能具有广阔的应用前景。

更新日期:2022-06-05
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