2. Academic Validation
  3. 4-octyl Itaconate Attenuates Acute Pancreatitis and Associated Lung Injury by Suppressing Ferroptosis in Mice

4-octyl Itaconate Attenuates Acute Pancreatitis and Associated Lung Injury by Suppressing Ferroptosis in Mice

  • Inflammation. 2025 Feb 7. doi: 10.1007/s10753-025-02256-x.
Shimin Lu # 1 2,  Yang Gong # 2 3,  Pengzhan He 2 4,  Mingming Qi 5,  Weiguo Dong 6 7
Affiliations

Affiliations

  • 1 Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
  • 2 Central Laboratory of Renmin Hospital, Wuhan, 430060, Hubei Province, China.
  • 3 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
  • 4 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.
  • 5 Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang Province, China.
  • 6 Central Laboratory of Renmin Hospital, Wuhan, 430060, Hubei Province, China. dongweiguo@whu.edu.cn.
  • 7 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China. dongweiguo@whu.edu.cn.
  • # Contributed equally.
PMID: 39920558 DOI: 10.1007/s10753-025-02256-x
Abstract

Acute pancreatitis (AP) is a common gastrointestinal emergency requiring hospitalization. In recent years, several studies have demonstrated a role for 4-octyl itaconate (4-OI) in anti-inflammatory and oxidative stress injury. However, the potential effects of 4-OI in AP have not been investigated. Caerulein and LPS were used to induce experimental AP models in mice and AR42J cells and then studied by histopathology, biochemical, and molecular analysis. Ferroptosis inhibitor ferrostatin-1 effectively improves pancreatic injury and reduces lipid peroxidation products in experimental AP mice. 4-OI treatment significantly alleviated pancreatic and AP-associated lung injury and inflammation in experimental AP mice by inhibiting Ferroptosis. The Ferroptosis Activator Erastin blocked the protective effect of 4-OI against pancreatic injury in AP, validating that 4-OI alleviates pancreatitis injury through Ferroptosis. In vitro experiments further confirmed that 4-OI treatment ameliorated AP-induced pancreatic injury by inhibiting Ferroptosis. Our study, for the first time, found that 4-OI ameliorates AP and AP-related lung injury by inhibiting Ferroptosis in experimental AP mice, providing a new therapeutic target for alleviating AP.

Keywords

4-octyl itaconate; Acute pancreatitis; Ferroptosis; Inflammation.

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