Urolithin A alleviates acute kidney injury induced by renal ischemia reperfusion through the p62-Keap1-Nrf2 signaling pathway

被引:21
|
作者
Zhang, Yi [1 ,2 ]
Liu, Mengmeng [2 ]
Zhang, Yaoyuan [1 ]
Tian, Mi [2 ]
Chen, Peng [1 ]
Lan, Yu [2 ]
Zhou, Benhong [1 ,2 ]
机构
[1] Wuhan Univ, Dept Pharm, Renmin Hosp, Wuhan 430071, Hubei, Peoples R China
[2] Wuhan Univ, Sch Pharmaceut Sci, Wuhan, Peoples R China
基金
中国国家自然科学基金;
关键词
acute kidney injury; antioxidant; p62-Keap1-Nrf2 signaling pathway; renal ischemia reperfusion; Urolithin A; CISPLATIN-INDUCED NEPHROTOXICITY; AUTOPHAGY; APOPTOSIS; ELLAGITANNINS; ANTIOXIDANT; INFLAMMATION; METABOLISM; DISEASE; HEALTH;
D O I
10.1002/ptr.7370
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Acute kidney injury (AKI) induced by renal ischemia reperfusion (RIR) is typically observed in renal surgeries and is a leading cause of renal failure. However, there is still an unmet medical need currently in terms of clinical treatments. Herein, we report the effect of Urolithin A (UA) in a mouse RIR model, wherein we demonstrated its underlying mechanism both in vitro and in vivo. The expression levels of p62 and Keap1 significantly decreased, while that of nuclear Nrf2 increased in vitro in a hypoxia cell model after UA treatment. Furthermore, the apoptosis of tubular cells was attenuated and the reactive oxygen species (ROS) levels were reduced in the kidneys in a mouse RIR model after UA administration. In this study, we demonstrated that UA can alleviate oxidative stress and promote autophagy by activating the p62-Keap1-Nrf2 signaling pathway, which could protect the kidneys from ischemia reperfusion injury.
引用
收藏
页码:984 / 995
页数:12
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