Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis

This graphic illustrates the role of the Nrf2-mediated pathway in salidroside (Sal)-mediated protection against LIRI ferroptosis. LIRI induces ferroptosis by increasing iron accumulation and lipid peroxidation as well as inhibiting System Xc-. Nonetheless, ferroptosis cells produce chemokines like CCL2 and CCL12, which cause macrophage migration and, ultimately, inflammation in LIRI. Sal activates Nrf2 signaling and causes Keap1-Nrf2 dissociation and the stabilization of Nrf2 proteins. This stabilized Nrf2 protein translocates to the cell nucleus, where it binds to antioxidant response elements (AREs) and stimulates the expression of SLC7A11 and GPX4, thus inhibiting ferroptosis.