2. Academic Validation
  3. Ticlopidine protects hepatic ischemia-reperfusion injury via suppressing ferroptosis

Ticlopidine protects hepatic ischemia-reperfusion injury via suppressing ferroptosis

  • Biochem Biophys Res Commun. 2024 Jul 23:733:150436. doi: 10.1016/j.bbrc.2024.150436.
Yanni Ma 1,  Xintong Yao 1,  Yunding Zou 1,  Baiping Liu 2,  Yuanze Zhou 1,  Zhenzhen Guo 3,  Qi Yao 4,  Shuangnian Xu 5,  Hui Li 6
Affiliations

Affiliations

  • 1 Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400030, China.
  • 2 Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401120, China.
  • 3 Hunan University of Humanities, Science and Technology, Loudi, Hunan province, 417000, China.
  • 4 Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400030, China. Electronic address: yaoqiwh@tmmu.edu.cn.
  • 5 Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400030, China. Electronic address: xushuangnian@tmmu.edu.cn.
  • 6 Department of Hematology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400030, China; Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children (Women and Children's Hospital of Chongqing Medical University), Chongqing, 401120, China. Electronic address: lihui1983@tmmu.edu.cn.
PMID: 39053102 DOI: 10.1016/j.bbrc.2024.150436
Abstract

Hepatic ischemia-reperfusion injury (IRI) is a major cause of liver damage during hepatic resection, transplantation, and Other surgical procedures, often leading to graft failure and liver dysfunction. Recent studies have identified Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, as a key contributor to IRI. In this study, we investigated the protective effects of Ticlopidine, a thienopyridine compound and platelet aggregation inhibitor, on hepatic IRI. Using a C57BL/6J mouse model, we demonstrated that prophylactic Ticlopidine treatment significantly reduced necrotic and fibrotic areas in liver tissues, as well as serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST). Prussian Blue staining revealed that Ticlopidine pretreatment decreased iron accumulation in hepatic tissues, whereas markers of lipid peroxidation (malondialdehyde and 4-hydroxynonenal) and Ferroptosis (PTGS2) were significantly downregulated. Additionally, Ticlopidine ameliorated inflammatory infiltration as indicated by reduced Gr-1 staining. In vitro, Ticlopidine dose-dependently inhibited Ferroptosis induced by various inducers in liver Cancer cell lines HUH7 and fibrosarcoma cells HT1080. The protective effects involved partial rescue of lipid peroxidation, significant reduction of ferrous iron levels, and strong protection against mitochondrial damage. These findings suggested that Ticlopidine acts as a broad-spectrum Ferroptosis inhibitor, offering a promising therapeutic approach for protecting the liver against IRI.

Keywords

Ferroptosis; Hepatic ischemia-reperfusion injury; Ticlopidine.

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