2. Academic Validation
  3. Tetramethylpyrazine inhibits neutrophil extracellular traps formation and alleviates hepatic ischemia/reperfusion injury in rat liver transplantation

Tetramethylpyrazine inhibits neutrophil extracellular traps formation and alleviates hepatic ischemia/reperfusion injury in rat liver transplantation

  • Exp Cell Res. 2021 Sep 1;406(1):112719. doi: 10.1016/j.yexcr.2021.112719.
Yanyao Liu 1,  Xiaoyan Qin 2,  Zilun Lei 1,  Hao Chai 1,  Zuotian Huang 1,  Zhongjun Wu 3
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of General Surgery of Yuzhong District, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
  • 3 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: wzjtcy@126.com.
PMID: 34273405 DOI: 10.1016/j.yexcr.2021.112719
Abstract

Hepatic ischemia/reperfusion injury (IRI) is an adverse effect for liver transplantation which is characterized by immune response mediated inflammation. Recent studies report that neutrophil extracellular traps (NETs) are implicated in hepatic IRI. The aim of this study was to explore the mechanism of action of tetramethylpyrazine (TMP), the main chemical composition of Ligusticum chuanxiong in treatment of ischemic related diseases. Data showed that hepatic IRI increases the leak of alanine aminotransferase (ALT) and aspartate transaminase (AST), and stimulates formation of NETs. Extracellular DNA/NETs assay, hematoxylin-eosin (HE) staining, immunofluorescence assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and Western blot assay, showed that TMP significantly reduces formation of NETs and alleviates hepatic IRI. Moreover, TMP and Diphenyleneiodonium (DPI) suppressed ROS production in neutrophils. In addition, analysis showed that activation of NADPH Oxidase plays a role in formation of NETs triggered by hepatic IRI. Notably, TMP inhibited formation of NETs though inhibition of NADPH Oxidase. Additionally, Combination treatment using TMP and DPI was more effective compared with monotherapy of either of the two drugs. These findings show that combination therapy using TMP and DPI is a promising method for treatment hepatic IRI.

Keywords

Hepatic ischemia reperfusion injury; Liver transplantation; NADPH oxidase; Neutrophil extracellular traps (NETs); Tetramethylpyrazine (TMP).

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