Ferroptosis inhibition enhances liver and lung graft function
Ischemia-reperfusion injury (IRI) is a major clinical challenge in transplantation, vascular surgeries, myocardial infarction, and stroke. Disruption of energy and redox homeostasis triggers ferroptosis, a regulated, iron-dependent form of cell death, leading to organ dysfunction. We identify an early and transient increase of lipid peroxidation in human liver transplants and validate it as a therapeutic target. FXT-001, a ferroptosis inhibitor with dual radical and iron-trapping activity, provides robust protection in preclinical models, including ex situ perfusion of porcine liver and lung grafts. In a split ex vivo machine perfusion setting using declined human donors, FXT-001 treatment preserves graft viability, whereas untreated lungs deteriorate. We also develop FXT-002 and FXT-003 with enhanced pharmacokinetic and safety profiles. These findings support the use of ferroptosis inhibitors as a therapeutic strategy in transplantation and other IRI-associated conditions.
Authors
- Koen Augustyns (ORCID: https://orcid.org/0000-0002-5203-4339)
- Christine Gaillet
- Greta Klejborowska (ORCID: https://orcid.org/0000-0001-9365-4238)
- Dieter Van Beersel (ORCID: https://orcid.org/0000-0001-6492-7989)
- Joris Blondeel (ORCID: https://orcid.org/0000-0001-8531-8365)
- Behrouz Hassannia
- Camilla Scarpellini (ORCID: https://orcid.org/0000-0002-1860-6532)
- Jan‐Michael Abicht (ORCID: https://orcid.org/0000-0001-7361-1249)
- Caroline Lanthier (ORCID: https://orcid.org/0000-0002-5814-3173)
- Nicholas Gilbo (ORCID: https://orcid.org/0000-0001-6456-7071)
- J. Pirenne
- Ina Jochmans (ORCID: https://orcid.org/0000-0003-4592-2810)
- Ludovic Colombeau (ORCID: https://orcid.org/0000-0001-5823-2603)
- Laurens J. Ceulemans (ORCID: https://orcid.org/0000-0002-4261-7100)
- Michele Wölk (ORCID: https://orcid.org/0000-0001-5558-4582)
- B Reichart
- Geraldine Veeckmans (ORCID: https://orcid.org/0000-0002-4597-9692)
- Lene Devos (ORCID: https://orcid.org/0000-0001-6247-3696)
- Magali Walravens
- H. Winter
- Sebastian Müller
- Matthias Längin
- Martin Bender
- Arne Neyrinck
- Diethard Monbaliu
- Maria Fedorova
- Raphaël Rodriguez
- Tom Vanden Berghe (ORCID: https://orcid.org/0000-0002-1633-0974)
Institutions
- Centre National de la Recherche Scientifique (FR)
- University of Antwerp (BE)
- Inserm (FR)
- University of Liège (BE)
- Université Paris Sciences et Lettres (FR)
- LMU Klinikum (DE)
- University Hospital Carl Gustav Carus (DE)
- Technische Universität Dresden (DE)
- Ludwig-Maximilians-Universität München (DE)
- KU Leuven (BE)
Publication Details
- Journal
- Cell
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1016/j.cell.2026.04.024
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Fonds Wetenschappelijk Onderzoek
- Stichting Tegen Kanker
- Universiteit Antwerpen