Ferroptosisand Its Role in the Treatment of Sepsis-Related Organ Injury: Mechanisms and Potential Therapeutic Approaches

Abstract

Pengyu Zhang,1 Wendi Liu,2 Shu Wang,2 Yuan Wang,3 Han Han2 1The Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2School of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3Department of Histology and Embryology, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yuan Wang, Email [email protected]: Sepsis is a complicated clinical disease caused by a defective host response to infection, leading to elevated morbidity and fatality globally. Sepsis patients have a significant risk of life-threatening organ damage, including hearts, brains, lungs, kidneys, and livers. Nevertheless, the molecular pathways driving organ injury in sepsis are not well known. Ferroptosis, a non-apoptotic cell death, occurs due to iron metabolism disturbance and lipid peroxide buildup. Multiple studies indicate that ferroptosis has a significant role in decreasing inflammation and lipid peroxidation during sepsis. Ferroptosis inhibitors and medications, aimed at the most studied ferroptosis process, including Xc−system, Nrf2/GPX4 axis, and NCOA4-FTH1-mediated ferritinophagy, alleviating sepsis effectively. However, few clinical trials demonstrated ferroptosis-targeted drugs’s effectiveness in sepsis. Our study examines ferroptosis-targeted medicinal agents and their potential benefits for treating sepsis-associated organ impairment. This review indicates that ferroptosis suppression by pharmaceutical means may be a useful therapy for sepsis-associated organ injury.Keywords: sepsis, ferroptosis, sepsis-associated organ injury, ferroptosis inhibitor, medications

Keywords

• sepsis
• ferroptosis
• sepsis-associated organ injury
• ferroptosis inhibitor
• medications