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 iron-dependent 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, sepsis-associated 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 sepsis-related 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 sepsis-related organ damage.

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