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普鲁士蓝纳米酶通过减轻氧化应激和调节炎症来预防蒽环类药物诱导的肝损伤。

Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation.

机构信息

State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210096, P. R. China.

Department of Head & Neck Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210029, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2021 Sep 15;13(36):42382-42395. doi: 10.1021/acsami.1c09838. Epub 2021 Sep 2.

Abstract

Anthracycline-induced liver injury (AILI) is becoming an increasingly serious and potential clinical complication and is linked to reactive oxygen species (ROS) production and subsequent inflammatory response. Herein, we demonstrated that artificial Prussian blue nanozymes (PBZs) prevented daunorubicin-induced liver injury, a prototype of AILI, by attenuating ROS production and regulating inflammation. PBZs exhibited multienzyme activity and could scavenge ROS and free radicals. At the cellular level, PBZs could effectively eliminate ROS, suppress hepatocyte apoptosis, reduce deoxyribonucleic acid damage, and decrease the levels of inflammatory cytokines and chemokines. According to the results of the in vivo study, pretreatment with PBZs also resulted in a desirable protective effect against AILI, as indicated by both a decrease in biochemical indicator levels and hepatocyte necrosis. PBZs upregulated antioxidative genes by activating the Nrf2 pathway to reduce oxidative stress. Meanwhile, PBZs counteracted the inflammatory response based on the decreased expression levels of myeloperoxidase and F4/80 in the liver. Collectively, our findings indicate that PBZ-based nanotherapy is a novel strategy for protecting against AILI.

摘要

蒽环类药物诱导的肝损伤 (AILI) 正成为一种日益严重且潜在的临床并发症,与活性氧 (ROS) 产生及随后的炎症反应有关。在此,我们证明了人工普鲁士蓝纳米酶 (PBZs) 通过减轻 ROS 产生和调节炎症反应,预防了蒽环类药物诱导的肝损伤,即 AILI 的原型。PBZs 具有多种酶活性,可清除 ROS 和自由基。在细胞水平上,PBZs 可以有效清除 ROS,抑制肝细胞凋亡,减少脱氧核糖核酸损伤,并降低炎症细胞因子和趋化因子的水平。根据体内研究结果,PBZs 预处理对 AILI 也具有良好的保护作用,表现在生化指标水平降低和肝细胞坏死减少。PBZs 通过激活 Nrf2 通路上调抗氧化基因,减少氧化应激。同时,PBZs 基于肝脏中髓过氧化物酶和 F4/80 表达水平的降低来对抗炎症反应。综上所述,我们的研究结果表明,基于 PBZ 的纳米疗法是一种预防 AILI 的新策略。

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