{
  "abstract": "Macrophage migration inhibitory factor (MIF) is an early mediator of ischemia–reperfusion injury (IRI), however, the evidence on its role in orthotopic liver transplantation (OLT), particularly with donation after circulatory death (DCD) grafts is limited. Given its key regulatory function, this study investigated the effects of IRI on graft injury and assessed whether the use of ISO-1, a small-molecule MIF-inhibitor, affect IRI in a rat DCD-OLT model. 196 male Lewis rats were randomized into DBD control, DCD-30 min, DCD-60 min, DCD-30 + ISO-1, and DCD-30 + vehicle groups (n = 7/group/time-point). ISO-1 was administered before controlled cardiac arrest (0–60 min) and 3 h cold preservation before arterialized OLT. Animals were sacrificed at 1, 3, 24, and 168 h post-reperfusion. DCD grafts showed marked injury, with the DCD-60 group exhibiting lethal IRI. ISO-1 significantly reduced early hepatocellular injury compared with vehicle (AST:294 ± 63 vs 867 ± 211 IU/L, p = 0.017) and resulted in values comparable to DBD controls. Serum HMGB-1 (11 ± 2.8 vs 26 ± 6.2 pg/mL, p = 0.045) and MIF (45 ± 5.3 vs 144 ± 27.5 ng/mL, p = 0.034) levels were similarly decreased following ISO-1 application. ISO-1 improved graft microcirculation at 24 h, attenuated histological injury, and was associated with an altered time course of CD163 + macrophage infiltration. ISO-1 pre-treatment attenuated hepatocellular injury and was associated with improved graft microcirculation and reduced DAMP release, supporting further mechanistic and translational evaluation in DCD liver transplantation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria.",
    "Institute for Laboratory Animal Science and Experimental Surgery, Faculty of Medicine, University Hospital RWTH Aachen, Aachen, Germany.",
    "Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital, Würzburg, Germany.",
    "Department of Cardiac Anaesthesiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Berlin, Germany.",
    "Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.",
    "Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.",
    "Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Aachen, Germany.",
    "Cardiovascular Critical Care & Anesthesia research and evaluation (3CARE), University Hospital RWTH Aachen, Aachen, Germany.",
    "Department of Intensive Care Medicine, RWTH Aachen University, Aachen, Germany.",
    "Department of General, Visceral, Vascular, and Transplantation Surgery, University Hospital Essen, Essen, Germany.",
    "Faculty of Medicine, University Duisburg-Essen, Essen, Germany."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Deniz Uluk"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjia Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Decan Jiang",
      "orcid": "0000-0003-0535-9488"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Christian Stoppe",
      "orcid": "0000-0002-2028-2039"
    },
    {
      "affs": [
        5
      ],
      "name": "Franziska Alexandra Meister"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Sandra Kraemer"
    },
    {
      "affs": [
        8
      ],
      "name": "Christian Beckers"
    },
    {
      "affs": [
        8
      ],
      "name": "Alexander Theissen"
    },
    {
      "affs": [
        8
      ],
      "name": "Christian Bleilevens"
    },
    {
      "affs": [
        9
      ],
      "name": "Jan Bednarsch",
      "orcid": "0000-0001-8143-6452"
    },
    {
      "affs": [
        9
      ],
      "name": "Ulf Peter Neumann"
    },
    {
      "affs": [
        1
      ],
      "name": "Rene Hany Tolba"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Zoltan Czigany",
      "orcid": "0009-0004-9327-6440"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/558vhzk7ehf6k.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0361214",
  "fulltext_url": "https://europepmc.org/articles/PMC13704867",
  "id": "558vhzk7ehf6k",
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    "1932-6203"
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  "landing_url": "https://doi.org/10.1371/journal.pone.0361214",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "2746|Organ Transplantation Techniques and Outcomes"
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    ],
    [
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      "/Medicine and health sciences/Surgical and invasive medical procedures/Digestive system procedures/Liver transplantation"
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    [
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    ],
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  "pdf_url": "https://europepmc.org/articles/PMC13704867?pdf=render",
  "pmcid": "PMC13704867",
  "pmid": "42932262",
  "published": "2026-10-26",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/558vhzk7ehf6k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:17Z",
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  "subjects": [
    {
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      "origin": "plos:cell biology",
      "subfield": "cell-biology"
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      "field": "medicine",
      "origin": "plos:anatomy",
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  ],
  "title": "MIF inhibitor ISO-1 attenuates ischemia-reperfusion injury in a rat model of donation after circulatory death liver transplantation",
  "title_text": "MIF inhibitor ISO-1 attenuates ischemia-reperfusion injury in a rat model of donation after circulatory death liver transplantation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:51Z",
  "url": "https://research.draconitic.com/paper/558vhzk7ehf6k",
  "venue": "PLOS One",
  "versions": []
}