2. Academic Validation
  3. Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice

Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice

  • World J Hepatol. 2024 Oct 27;16(10):1188-1198. doi: 10.4254/wjh.v16.i10.1188.
Chun-Mei Li 1 2 3 4,  Tian Sun 1 2 3 4,  Mou-Jie Yang 1 2,  Zhi Yang 1 2 3 4,  Qing Li 1 2 3 4,  Jia-Lin Shi 1 2,  Chong Zhang 1 2 3 4,  Jun-Fei Jin 1 2 3 5
Affiliations

Affiliations

  • 1 Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China.
  • 2 Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China.
  • 3 China-United States Lipids in Health and Disease Research Center, Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China.
  • 4 Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China.
  • 5 Laboratory of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China. changliangzijin@163.com.
PMID: 39474574 DOI: 10.4254/wjh.v16.i10.1188
Abstract

Background: Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen (APAP). However, the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear.

Aim: To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation.

Methods: A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury. C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment. We detected the effects of C2-FH on liver function, inflammatory response and complement activation. Additionally, RNA-sequencing (RNA-Seq) analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury.

Results: C2-FH inhibited the increase in serum alanine aminotransferase activity, aspartate aminotransferase activity and Lactate Dehydrogenase, and reduced liver tissue necrosis caused by APAP. Moreover, it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury. RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury.

Conclusion: C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.

Keywords

Acetaminophen-induced liver injury; C2-FH; Complement; Complement activation; Inflammation.

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