The Emerging Role of Ferroptosis in Sepsis, Opportunity or Challenge?

Abstract

Qigang Huang, Yingwei Ding, Chao Fang, Hao Wang, Laifa Kong Department of Emergency Medicine, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, Zhejiang, People’s Republic of ChinaCorrespondence: Laifa Kong, Department of Emergency Medicine, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, Zhejiang, People’s Republic of China, Email [email protected]: Sepsis is a syndrome in multi-organ dysfunction triggered by a deleterious immunological reaction of the body to a condition caused by infection, surgery, or trauma. Currently, sepsis is thought to be primarily associated with abnormal immune responses resulting in organ microcirculatory disturbances, cellular mitochondrial dysfunction, and induced cell death, although the exact pathogenesis of sepsis is still inconclusive. In recent years, the role of abnormal metabolism of trace nutrients in the pathogenesis of sepsis has been investigated. Ferroptosis is a type of cell death that relies on iron and is characterized by unique morphological, biochemical, and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily driven by lipid peroxidation. Ferroptosis cells may be immunogenic, amplify inflammatory responses, cause more cell death, and ultimately induce multi-organ failure. An increasing number of studies have indicated the significance of ferroptosis in sepsis and its role in reducing inflammation. The effectiveness of sepsis treatment has been demonstrated by the use of drugs that specifically target molecules associated with the ferroptosis pathway, including ferroptosis inhibitors. Nevertheless, there is a scarcity of studies investigating the multi-organ dysfunction caused by ferroptosis in sepsis. This article presents a summary and evaluation of recent progress in the role of ferroptosis through molecularly regulated mechanisms and its potential mechanisms of action in the multi-organ dysfunction associated with sepsis. It also discusses the current challenges and prospects in understanding the connection between sepsis and ferroptosis, and proposes innovative ideas and strategies for the treatment of sepsis.Keywords: sepsis, ferroptosis, organ damage, lipid peroxidation, treatment

Keywords

• sepsis
• ferroptosis
• organ damage
• lipid peroxidation
• treatment