{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:43:15Z","timestamp":1790674995121,"version":"4.1.0"},"reference-count":123,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["P01 AI120944"],"award-info":[{"award-number":["P01 AI120944"]}]},{"name":"NIH","award":["R01 DK062357"],"award-info":[{"award-number":["R01 DK062357"]}]},{"name":"NIH","award":["R01 AI155856-01"],"award-info":[{"award-number":["R01 AI155856-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Reactive oxygen species (ROS) play a dual role as both essential signaling molecules and harmful mediators of damage. Imbalances in the redox state of the liver can overwhelm antioxidant defenses and promote mitochondrial dysfunction, oxidative damage, and inflammation. Complex feedback loops between ROS and immune signaling pathways are a hallmark of pathological liver conditions, such as hepatic ischemia\u2013reperfusion injury (IRI). This is a major cause of liver transplant failure and is of increasing significance due to the increased use of marginally discarded livers for transplantation. This review outlines the major enzymatic and metabolic sources of ROS in hepatic IRI, including mitochondrial reverse electron transport, NADPH oxidases, cytochrome P450 enzymes, and endoplasmic reticulum stress. Hepatocyte injury activates redox feedback loops that initiate immune cascades through DAMP release, toll-like receptor signaling, and cytokine production. Emerging regulatory mechanisms, such as succinate accumulation and cytosolic calcium\u2013CAMKII signaling, further shape oxidative dynamics. Pharmacological therapies and the use of antioxidant and immunomodulatory approaches, including nanoparticles and redox-sensitive therapeutics, are discussed as protective strategies. A deeper understanding of how redox and immune feedback loops interact is an exciting and active area of research that warrants further clinical investigation.<\/jats:p>","DOI":"10.3390\/antiox14080944","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Feedback Loops Shape Oxidative and Immune Interactions in Hepatic Ischemia\u2013Reperfusion Injury"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-4092","authenticated-orcid":false,"given":"Kenneth J.","family":"Dery","sequence":"first","affiliation":[{"name":"Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aanchal","family":"Kasargod","sequence":"additional","affiliation":[{"name":"Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy W.","family":"Kupiec-Weglinski","sequence":"additional","affiliation":[{"name":"Division of Liver and Pancreas Transplantation, Department of Surgery, The Dumont-UCLA Transplantation Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","first-page":"100176","article-title":"Targeting Ischemia-reperfusion injury in liver transplant rejuvenation","volume":"10","author":"Dery","year":"2025","journal-title":"Transplant. 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