2. Academic Validation
  3. Protective effect of taraxasterol on ischemia/reperfusion-induced acute kidney injury via inhibition of oxidative stress, inflammation, and apoptosis

Protective effect of taraxasterol on ischemia/reperfusion-induced acute kidney injury via inhibition of oxidative stress, inflammation, and apoptosis

  • Int Immunopharmacol. 2020 Dec;89(Pt A):107169. doi: 10.1016/j.intimp.2020.107169.
Chuanlei Li 1,  Zhihuang Zheng 2,  Yun Xie 3,  Nan Zhu 4,  Jinfang Bao 5,  Qing Yu 6,  Zhigang Zhou 7,  Jun Liu 8
Affiliations

Affiliations

  • 1 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: lichuanlei@sjtu.edu.cn.
  • 2 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: 851124zzh@sjtu.edu.cn.
  • 3 Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: yun.xie@shgh.cn.
  • 4 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: znnancy@yeah.net.
  • 5 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: bamboobao@163.com.
  • 6 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: yuqingsl0618@163.com.
  • 7 Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: zhou_zhigang1980@163.com.
  • 8 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic address: liujun-sgh@sjtu.edu.cn.
PMID: 33183976 DOI: 10.1016/j.intimp.2020.107169
Abstract

Ischemia/reperfusion injury (IRI), the most common cause of acute kidney injury (AKI), is correlated with oxidative stress and subsequent inflammation. Taraxasterol, a natural product, has been shown to exert anti-oxidative and anti-inflammatory effects. However, the role of taraxasterol in renal IRI remains unknown. In this study, mice were subjected to 30 min of bilateral renal ischemia-reperfusion to induce AKI. Cellular hypoxia/reoxygenation (H/R) was used to mimic IRI in vitro. Western blotting, immunochemistry, immunofluorescence, TUNEL staining, ELISA, and flow cytometry were performed to evaluate kidney damage, oxidative stress, inflammation, and Apoptosis in vivo and in vitro. Treatment with taraxasterol attenuated the following in a dose-dependent manner: tubular damage; infiltration of F4/80-positive macrophages; renal interstitial fibrosis; myeloperoxidase (MPO) activity; and expression of the inflammatory cytokines tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1). Moreover, taraxasterol treatment remarkably ameliorated Apoptosis in the kidney by decreasing Bax expression and conserving Bcl2. Notably, MitoSOX assay revealed that treatment with taraxasterol suppressed the production of mitochondrial Reactive Oxygen Species. Furthermore, taraxasterol suppressed phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signaling pathways in vivo and in vitro. In conclusion, these findings indicate that taraxasterol has a protective effect on IRI-induced AKI via inhibition of oxidative stress, inflammation, and Apoptosis.

Keywords

Acute kidney injury; Apoptosis; Inflammation; Oxidative stress; Taraxasterol.

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