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Review
. 2022 Sep;289(18):5463-5479.
doi: 10.1111/febs.16336. Epub 2022 Jan 19.

Nrf2 and oxidative stress in liver ischemia/reperfusion injury

Raquel G Bardallo  1 , Arnau Panisello-Roselló  2 , Sergio Sanchez-Nuno  1 , Norma Alva  1 , Joan Roselló-Catafau  2 , Teresa Carbonell  1
Affiliations
Free article
Review

Nrf2 and oxidative stress in liver ischemia/reperfusion injury

Raquel G Bardallo et al. FEBS J. 2022 Sep.
Free article

Abstract

In response to stress signal, nuclear factor-erythroid 2-related factor 2 (Nrf2) induces the expression of target genes involved in antioxidant defense and detoxification. Nrf2 activity is strictly regulated through a variety of mechanisms, including regulation of Keap1-Nrf2 stability, transcriptional regulation (NF-ĸB, ATF3, ATF4), and post-transcriptional regulation (miRNA), evidencing that transcriptional responses of Nrf2 are critical for the maintenance of homeostasis. Ischemia-reperfusion (IR) injury is a major cause of graft loss and dysfunction in clinical transplantation and organ resection. During the IR process, the generation of reactive oxygen species (ROS) leads to damage from oxidative stress, oxidation of biomolecules, and mitochondrial dysfunction. Oxidative stress can trigger apoptotic and necrotic cell death. Stress factors also result in the assembly of the inflammasome protein complex and the subsequent activation and secretion of proinflammatory cytokines. After Nrf2 activation, the downstream antioxidant upregulation can act as a primary cellular defense against the cytotoxic effects of oxidative stress and help to promote hepatic recovery during IR. The complex crosstalk between Nrf2 and cellular pathways in liver IR injury and the potential therapeutic target of the Nrf2 inducers will be discussed in the present review.

Keywords: Nrf2; antioxidant; inflammation; ischemia-reperfusion injury; liver; redox.

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References

    1. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190:255-66.
    1. Raedschelders K, Ansley DM, Chen DDY. The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion. Pharmacol Ther. 2012;133:230-55. https://doi.org/10.1016/j.pharmthera.2011.11.004.
    1. Zaouali MA, Abdennebi HB, Padrissa-Altés S, Mahfoudh-Boussaid A, Roselló-Catafau J. Pharmacological strategies against cold ischemia reperfusion injury. Expert Opin Pharmacother. 2010;11:537-55. https://doi.org/10.1517/14656560903547836.
    1. Alva N, Bardallo RG, Basanta D, Palomeque J, Carbonell T. Preconditioning-like properties of short-term hypothermia in isolated perfused rat liver (IPRL) system. Int J Mol Sci. 2018;19:doi:https://doi.org/10.3390/ijms19041023.
    1. Jaeschke H, Woolbright BL. Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transplant Rev. 2012;26:103-14. https://doi.org/10.1016/j.trre.2011.10.006.

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