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

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