Pharmacological inhibition of ferroptosis as a therapeutic target for sepsis-associated organ damage

Sepsis is a complex clinical syndrome caused by dysfunctional host response to infection, which contributes to excess mortality and morbidity worldwide. The development of life-threatening sepsis-associated organ injury to the brain, heart, kidneys, lungs, and liver is a major concern for sepsis patients. However, the molecular mechanisms underlying sepsis-associated organ injury remain incompletely understood. Ferroptosis, an irondependent non-apoptotic form of cell death characterized by lipid peroxidation, is involved in sepsis and sepsis-related organ damage, including sepsis-associated encephalopathy, septic cardiomyopathy, sepsisassociated acute kidney injury, sepsis-associated acute lung injury, and sepsis-induced acute liver injury. Moreover, compounds that inhibit ferroptosis exert potential therapeutic effects in the context of sepsis-related organ damage. This review summarizes the mechanism by which ferroptosis contributes to sepsis and sepsisrelated organ damage. We focus on the emerging types of therapeutic compounds that can inhibit ferroptosis and delineate their beneficial pharmacological effects for the treatment of sepsis-related organ damage. The present review highlights pharmacologically inhibiting ferroptosis as an attractive therapeutic strategy for sepsisrelated organ damage.