2. Academic Validation
  3. CoQ10 alleviates hepatic ischemia reperfusion injury via inhibiting NLRP3 activity and promoting Tregs infiltration

CoQ10 alleviates hepatic ischemia reperfusion injury via inhibiting NLRP3 activity and promoting Tregs infiltration

  • Mol Immunol. 2023 Jan 12;155:7-16. doi: 10.1016/j.molimm.2023.01.005.
Shaopeng Zhang 1,  Xiaojie Gan 2,  Ji Gao 3,  Jie Duan 4,  Aidong Gu 5,  Changhao Chen 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing university of Chinese Medicine, Nanjing, China; Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 2 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
  • 3 Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing university of Chinese Medicine, Nanjing, China.
  • 5 Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing university of Chinese Medicine, Nanjing, China. Electronic address: xzgad@163.com.
  • 6 Department of Hepatobiliary Surgery, The Second Hospital of Nanjing, Nanjing university of Chinese Medicine, Nanjing, China. Electronic address: chenchanghao0514@163.com.
PMID: 36640727 DOI: 10.1016/j.molimm.2023.01.005
Abstract

Hepatic ischemia-reperfusion injury (IRI) has been concerned as a main complication of liver surgery and transplantation. Previous studies show that Reactive Oxygen Species (ROS) associated inflammation response and contribute to the liver damage during IRI. Coenzyme Q10 (CoQ10) has shown many beneficial effects on abrogating ROS production and ameliorating liver injury. This study found lower CoQ10 level in the process of liver IRI in a mouse model of hepatic IRI. Meanwhile, our results showed that CoQ10 administration significantly attenuate hepatic IRI proved by HE staining, serum ALT/AST. The NOD-like Receptor protein 3 (NLRP3) inflammasome is activated by ROS which triggers the activation of inflammatory caspases. In this study, NLRP3 was significantly suppressed by CoQ10 while Foxp3 exhibited increased expression in liver. Furthermore, Kupffer cells (KCs) pretreated with CoQ10 under the condition of hypoxia and reoxygenation contributed to improved CD4+CD25+Foxp3+ regulatory T cells (Tregs) ratio in co-culture system. Furthermore, NLRP3 inflammasome activator treatment in vivo resulted in higher expression of Caspase-1 and NLRP3 and reduction of Tregs in liver, which reversed the protection of CoQ10 in the liver injury. Taken together, our study discovered that CoQ10 can suppress NLRP3 activity in KCs and improves Foxp3+ Tregs differentiation depending on M2 macrophage polarization of KCs to ameliorate hepatic IRI.

Keywords

CoQ10; IRI; NLRP3; ROS; Tregs.

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