Kelch-like ech-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element pathway alleviates ferroptosis in sepsis by regulating oxidative stress

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and has a high morbidity and mortality worldwide. The characteristic of sepsis is the inflammatory reaction. Cytokines produced by the severe inflammatory reaction can activate neutrophils and cause excessive production of reactive oxygen species (ROS), thus damage cells and tissue, and further develop into organ dysfunction and failure. Ferroptosis is an iron-dependent form of nonapoptotic cell death discovered recently. Its main mechanism is the intracellular lipid peroxidation induced by iron and the low expression of antioxidant systems [glutathione (GSH) and glutathione peroxidase 4 (GPX4)]. Recently, many studies have shown that Kelch-like ech-associated protein 1/nuclear factor E2-related factor 2/antioxidant response element (Keap1/Nrf2/ARE) signal pathway can improve oxidative stress and alleviate ferroptosis in sepsis. This article reviews the molecular mechanism and research of Nrf2 inhibiting ferroptosis in sepsis, in order to innovate prevention and treatments for the intervention of sepsis.