Celastrol alleviated acute kidney injury by inhibition of ferroptosis through Nrf2/GPX4 pathway

被引：20

作者：

Pan, Minling ^{[1
]}

Wang, Zhen ^{[2
]}

Wang, Yiyi ^{[1
]}

Jiang, Xianqin ^{[2
]}

Fan, Yali ^{[1
]}

Gong, Fanghua ^{[2
]}

Sun, Yunpeng ^{[3
]}

Wang, Dezhong ^{[1
,3
]}

机构：

[1] Wenzhou Univ, Sch Life & Environm Sci, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325035, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2023年 / 166卷

基金：

中国国家自然科学基金;

关键词：

Celastrol; Cisplatin; Acute kidney injury; Ferroptosis; GPX4; CELL-DEATH; MECHANISMS; APOPTOSIS; FAILURE; IRON;

D O I：

10.1016/j.biopha.2023.115333

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：

Ferroptosis is an important pathological process in acute kidney injury (AKI) which could lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). As an active ingredient of Chinese medicine Tripterygium wilfordii, celastrol has been reported to alleviate inflammation and preclinical studies have confirmed its anti-cancer effect. In the present study, we investigated the renal protective effects of celastrol against cisplatin induced AKI. Mice were administrated cisplatin by intraperitoneal injection and we found that celastrol reduced serum levels of BUN and creatinine, inhibited renal dysfunction, inflammation and oxidative stress. In addition, renal iron accumulation and ferroptosis were significantly reduced by celastrol treatment. Further mechanistic analyses suggested that Nrf2 is essential for celastrol upregulated GPX4 to alleviate ferroptosis and reduction of LDH release, intracellular iron accumulation and lipid peroxidation. These findings expand the potential uses of celastrol for treatment of various kinds of AKI associated with ferroptosis.

引用

页数：10

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