2. Academic Validation
  3. 25-Hydroxycholesterol mitigates hepatic ischemia reperfusion injury via mediating mitophagy

25-Hydroxycholesterol mitigates hepatic ischemia reperfusion injury via mediating mitophagy

  • Int Immunopharmacol. 2021 Jul;96:107643. doi: 10.1016/j.intimp.2021.107643.
Qin Cao 1,  Jun Luo 1,  Yan Xiong 1,  Zhongzhong Liu 2,  Qifa Ye 3
Affiliations

Affiliations

  • 1 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Engineering Research Center of Natural Polymer-based Medical Materials in Hubei Province, Wuhan 430071, China.
  • 2 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Engineering Research Center of Natural Polymer-based Medical Materials in Hubei Province, Wuhan 430071, China. Electronic address: liuzhongzhong28@163.com.
  • 3 Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Engineering Research Center of Natural Polymer-based Medical Materials in Hubei Province, Wuhan 430071, China; The Third Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, China. Electronic address: yqf_china@163.com.
PMID: 33878616 DOI: 10.1016/j.intimp.2021.107643
Abstract

Hepatic ischemia reperfusion (I/R) injury remains a major obstacle in liver transplantation, however an effective treatment to mitigate this injury is lacking. 25-Hydroxycholesterol (25HC) is a kind of oxysterol involved in inflammatory and immune responses. However, its function and the underlying mechanism on rat hepatic I/R injury has not been explored. A well-established rat model of partial warm ischemia reperfusion injury was performed. 25HC was intraperitoneally administrated 4 h before ischemia. The results verified that 25HC pretreatment effectively mitigated liver I/R injury, which was demonstrated by lower serum levels of transaminases, histology injury score and less Apoptosis. Mechanistically, 25HC pretreatment activated PINK1/Parkin dependent Mitophagy and inhibited the NLRP3 inflammasome. Via using Mitophagy inhibitor 3-methyladenine (3-MA), we further found that 3-MA counteracted the protective effect of 25HC on hepatic I/R injury and the NLRP3 inflammasome. In conclusion, 25HC pretreatment ameliorates rat hepatic I/R injury, and this protective effect may be dependent on activating Mitophagy and inhibiting NLRP3 inflammasome activation.

Keywords

25-Hydroxycholesterol; Hepatic I/R injury; Mitophagy; NLRP3 inflammasome.

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