Introduction: Ischemia-Reperfusion (I/R) injury is a result of restoration of blood flow after a period of ischemia, which results in more tissue damage due to oxidative stress, inflammation, mitochondrial dysfunction, and Ca2+ overload. Various organs like the heart, brain, liver, and kidneys are highly sensitive to I/R injury, which results in apoptosis, necroptosis, and ferroptosis. Methodology: The literature review on “Retinoid X Receptors Signaling in Multiple-Organ Ischemia/ Reperfusion Injury” was conducted using strategic search terms including cerebral, hepatic, I/R injury, myocardial, renal, and Retinoid X Receptors (RXRs). Peer-reviewed sources like PubMed, ScienceDirect, and Google Scholar were used, and only recent studies that were peer-reviewed and published in English were found in order to maintain consistency, reliability, and scientific rigor. Results: Recent studies proved that RXRs have a critical role in the regulation of genes responsible for ROS production, inflammation, and cell survival. Activation of RXRs showed protection in preclinical models of myocardial, cerebral, hepatic, and renal I/R injury. Discussion: Mechanisms mediated by RXR in various I/R injuries are by inhibition of the TGF-β/Smad signaling pathway, inhibition of neuroinflammation and ferroptosis, and the downregulation of NF-κB and NLRP3 activation. In addition, renal repair and the reduction of oxidative stress are also facilitated by the RXRs, underscoring their multifaceted protective roles. Conclusion: RXRs have great potential as therapeutic targets for I/R injury. Further study of the role of RXR signaling may lead to new therapeutic approaches and biomarkers that will enhance the outcome of I/R injury.
Isha et al. (2026) studied this question.