Research Papers:

Nanoparticle-mediated dual delivery of resveratrol and DAP5 ameliorates kidney ischemia/reperfusion injury by inhibiting cell apoptosis and inflammation

Yong Xu, Bo Zhang, Da Xie, Yu Hu, Hai-Lun Li, Li-Li Zhong, Hong-Wu Wang, Wei Jiang, Zun-Ping Ke and Dong-Hui Zheng _

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Oncotarget. 2017; 8:39547-39558. https://doi.org/10.18632/oncotarget.17135

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Yong Xu1,*, Bo Zhang2,*, Da Xie3,*, Yu Hu1, Hai-Lun Li1, Li-Li Zhong1, Hong-Wu Wang1, Wei Jiang1, Zun-Ping Ke4 and Dong-Hui Zheng1

1Department of Nephrology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China

2Department of Dermatology, Hubei Provincial Hospital of TCM, Hongshan, Wuhan, China

3Department of Nephrology, The Secend Affiliated Hospital of Nanjing Medical University, Nanjing, China

4Department of Cardiology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, China

*These authors have contributed equally to this study and share first authorship

Correspondence to:

Dong-Hui Zheng, email: [email protected]

Zun-Ping Ke, email: [email protected]

Keywords: Res-DAP5 nanoparticles, apoptosis, inflammation, ischemia-reperfusion, acute renal injury

Received: December 01, 2016    Accepted: February 12, 2017    Published: April 17, 2017


Ischemia reperfusion (I/R) injury is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. NMDA receptor inhibitor (DAP5) and resveratrol (Res) could ameliorate kidney I/R injury, but their use is limited by low aqueous solubility and poor stability. Here, we examined the potential protective effects of Res-DAP5 nanoparticles (NP) against renal I/R injury. Mice were subjected to renal ischemia for 30 min followed by reperfusion for 24 h. The results showed that Res-DAP5-NP could decreased serum creatinine (Cr) and urea nitrogen (BUN), alleviated tubular damage and oxidative stress. In addition, Res-DAP5-NP suppressed cell apoptosis, promoted the expression of p-DAPK, and inhibited the expression of p-CaMK and p-AKT. Furthermore, Res-DAP5-NP decreased the production of pro-inflammatory cytokines such as tumor necrosis factor-α, IL-1β, IL-6, and p-IκBα induced by renal I/R injury. In addition, Res-DAP5-NP also attenuated renal I/R injury in vivo, as manifested by increase in cell viability, SOD level, and the expression of p-DAPK, decreases in intracellular Ca2+ concentration and the expression of p-CaMK. Taken together, our findings indicates that Res-DAP5-NP could effectively protect renal I/R injury by inhibiting apoptosis and inflammation responses, possibly through AKT/NMDA/CaMK/DAPK and NF-κB pathways.

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