2. Academic Validation
  3. Celastrol alleviated acute kidney injury by inhibition of ferroptosis through Nrf2/GPX4 pathway

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

  • Biomed Pharmacother. 2023 Aug 18;166:115333. doi: 10.1016/j.biopha.2023.115333.
Minling Pan 1,  Zhen Wang 2,  Yiyi Wang 1,  Xianqin Jiang 2,  Yali Fan 1,  Fanghua Gong 3,  Yunpeng Sun 4,  Dezhong Wang 5
Affiliations

Affiliations

  • 1 School of Life and Environmental Science, Wenzhou University, Wenzhou, Zhejiang 325035, China.
  • 2 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • 3 School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: gongwenheng@163.com.
  • 4 The First Affiliated Hospital of Wenzhou Medical University, China. Electronic address: sunyunpeng504@163.com.
  • 5 School of Life and Environmental Science, Wenzhou University, Wenzhou, Zhejiang 325035, China; The First Affiliated Hospital of Wenzhou Medical University, China. Electronic address: dzwang2022@gmail.com.
PMID: 37598476 DOI: 10.1016/j.biopha.2023.115333
Abstract

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 Anticancer 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.

Keywords

Acute kidney injury; Celastrol; Cisplatin; Ferroptosis; GPX4.

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