PMID- 33183976
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20210603
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 89
IP  - Pt A
DP  - 2020 Dec
TI  - Protective effect of taraxasterol on ischemia/reperfusion-induced acute kidney 
      injury via inhibition of oxidative stress, inflammation, and apoptosis.
PG  - 107169
LID - S1567-5769(20)33636-5 [pii]
LID - 10.1016/j.intimp.2020.107169 [doi]
AB  - 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), 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.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Li, Chuanlei
AU  - Li C
AD  - Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong 
      University, School of Medicine, Shanghai 201620, China. Electronic address: 
      lichuanlei@sjtu.edu.cn.
FAU - Zheng, Zhihuang
AU  - Zheng Z
AD  - Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong 
      University, School of Medicine, Shanghai 201620, China. Electronic address: 
      851124zzh@sjtu.edu.cn.
FAU - Xie, Yun
AU  - Xie Y
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic 
      address: yun.xie@shgh.cn.
FAU - Zhu, Nan
AU  - Zhu N
AD  - Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong 
      University, School of Medicine, Shanghai 201620, China. Electronic address: 
      znnancy@yeah.net.
FAU - Bao, Jinfang
AU  - Bao J
AD  - Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong 
      University, School of Medicine, Shanghai 201620, China. Electronic address: 
      bamboobao@163.com.
FAU - Yu, Qing
AU  - Yu Q
AD  - Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong 
      University, School of Medicine, Shanghai 201620, China. Electronic address: 
      yuqingsl0618@163.com.
FAU - Zhou, Zhigang
AU  - Zhou Z
AD  - Department of Critical Care Medicine, Shanghai General Hospital, Shanghai 
      Jiaotong University, School of Medicine, Shanghai 201620, China. Electronic 
      address: zhou_zhigang1980@163.com.
FAU - Liu, Jun
AU  - Liu J
AD  - Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong 
      University, School of Medicine, Shanghai 201620, China. Electronic address: 
      liujun-sgh@sjtu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20201110
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Sterols)
RN  - 0 (Triterpenes)
RN  - 64SK2ERN9P (taraxasterol)
SB  - IM
MH  - Acute Kidney Injury/*drug therapy/pathology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Humans
MH  - Inflammation/*drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress/*drug effects
MH  - Reperfusion Injury/*pathology
MH  - Sterols/*pharmacology
MH  - Triterpenes/*pharmacology
OTO - NOTNLM
OT  - Acute kidney injury
OT  - Apoptosis
OT  - Inflammation
OT  - Oxidative stress
OT  - Taraxasterol
EDAT- 2020/11/14 06:00
MHDA- 2021/06/04 06:00
CRDT- 2020/11/13 05:38
PHST- 2020/06/19 00:00 [received]
PHST- 2020/10/15 00:00 [revised]
PHST- 2020/10/29 00:00 [accepted]
PHST- 2020/11/14 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2020/11/13 05:38 [entrez]
AID - S1567-5769(20)33636-5 [pii]
AID - 10.1016/j.intimp.2020.107169 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2020 Dec;89(Pt A):107169. doi: 10.1016/j.intimp.2020.107169. 
      Epub 2020 Nov 10.