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    Targeting Nrf2 in ischemia-reperfusion alleviation: From signaling networks to therapeutic targeting
    (Elsevier Inc., 2022) Sadrkhanloo, Mehrdokht; Entezari, Maliheh; Orouei, Sima; Zabolian, Amirhossein; Mirzaie, Amirreza; Maghsoudloo, Amin; Raesi, Rasoul; Asadi, Neda; Hashemi, Mehrdad; Zarrabi, Ali; Khan, Haroon; Mirzaei, Sepideh; Samarghandian, Saeed
    The nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of redox balance and it responds to various cell stresses that oxidative stress is the most well-known one. The Nrf2 should undergo nuclear translocation to exert its protective impacts and decrease ROS production. On the other hand, ischemic/reperfusion (I/R) injury is a pathological event resulting from low blood flow to an organ and followed by reperfusion. The I/R induces cell injury and organ dysfunction. The present review focuses on Nrf2 function in alleviation of I/R injury. Stimulating of Nrf2 signaling ameliorates I/R injury in various organs including lung, liver, brain, testis and heart. The Nrf2 enhances activity of antioxidant enzymes to reduce ROS production and prevent oxidative stress-mediated cell death. Besides, Nrf2 reduces inflammation via decreasing levels of pro-inflammatory factors including IL-6, IL-1? and TNF-?. Nrf2 signaling is beneficial in preventing apoptosis and increasing cell viability. Nrf2 induces autophagy to prevent apoptosis during I/R injury. Furthermore, it can interact with other molecular pathways including PI3K/Akt, NF-?B, miRNAs, lncRNAs and GSK-3? among others, to ameliorate I/R injury. The therapeutic agents, most of them are phytochemicals such as resveratrol, berberine and curcumin, induce Nrf2 signaling in I/R injury alleviation. © 2022