An enzyme-mimicking reactive oxygen species scavenger targeting oxidative stress-inflammation cycle ameliorates IR-AKI by inhibiting pyruvate dehydrogenase kinase 4

被引:1
作者
He, Wenfang [1 ]
Ding, Chenguang [2 ]
Lin, Ting [1 ]
Wang, Binqi [1 ]
Wang, Wenjing [3 ,4 ]
Deng, Zhichao [5 ]
Jin, Taian [1 ]
Shang, Yiwei [1 ]
Zheng, Danna [6 ]
Bai, Ting [7 ]
Zhang, Mingzhen [5 ]
Li, Runqing [8 ]
Jin, Juan [1 ]
He, Qiang [1 ]
机构
[1] Zhejiang Chinese Med Univ, Zhejiang Prov Hosp Chinese Med, Affiliated Hosp 1, Dept Nephrol, Hangzhou 310003, Zhejiang, Peoples R China
[2] Xi An Jiao Tong Univ, Nephropathy Hosp, Affiliated Hosp 1, Dept Kidney Transplantat, Xian 710061, Shaanxi, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Wenzhou 325024, Zhejiang, Peoples R China
[4] Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou 325024, Zhejiang, Peoples R China
[5] Xi An Jiao Tong Univ, Sch Basic Med Sci, Xian 710061, Shaanxi, Peoples R China
[6] Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Hangzhou Med Coll, Urol & Nephrol Ctr, Hangzhou 310003, Zhejiang, Peoples R China
[7] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Cardiovasc Med, Xian 710077, Shaanxi, Peoples R China
[8] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Radiol, Xian 710061, Shaanxi, Peoples R China
来源
THERANOSTICS | 2024年 / 14卷 / 19期
基金
中国国家自然科学基金;
关键词
Acute kidney injury; ROS scavenger; Antioxidant; Anti-Inflammatory; Pyruvate dehydrogenase kinase 4; ACUTE KIDNEY INJURY; CURCUMIN; COMPLEX;
D O I
10.7150/thno.101229
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Rationale: Ischemia-reperfusion-induced acute kidney injury (IR-AKI), characterized by the abrupt decline in renal function, is distinguished by the intricate interplay between oxidative stress and inflammation. In this study, a reactive oxygen species (ROS) scavenger-CF@PDA was developed to effectively target antioxidant and anti-inflammatory pathways to disrupt the oxidative stress-inflammation cycle in IR-AKI. Methods: UV-vis absorption spectra, FTIR spectra, and TEM were employed to determine the successful construction of CF@P. ABTS, TMB, and NBT analyses were performed to detect the antioxidant ability and enzyme-mimicking ability of CF@P. In vitro and in vitro, the antioxidant/anti-inflammatory effect of CF@P was detected by MTT, qPCR, fluorescence, and flow cytometry. Multi-omics revealed the mechanism of CF@P in IR-AKI therapy, and molecular docking was further used to determine the mechanism. MRI and photoacoustic imaging were employed to explore the dual-mode imaging capacity of CF@P in IR-AKI management. Results: CF@P could disrupt the oxidative stress-inflammatory cascade by scavenging ROS, reducing pro-inflammatory cytokines, and modulation of macrophage polarization. Subsequent multi-omics indicated that the renal protective effects may be attributed to the inhibition of pyruvate dehydrogenase kinase 4 (PDK4). Metabolomics demonstrated that CF@P could improve the production of antioxidant compounds and reduce nephrotoxicity. Additionally, CF@P exhibited promising capabilities in T1-MRI and photoacoustic imaging for AKI management. Conclusions: Collectively, CF@P, possessing antioxidant/anti-inflammatory properties by inhibiting PDK4, as well as imaging capabilities and superior biocompatibility, holds promise as a therapeutic strategy for IR-AKI.
引用
收藏
页码:7534 / 7553
页数:20
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