Ferroptosis inhibition enhances liver and lung graft function
Summary
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,
Content
# Ferroptosis inhibition enhances liver and lung graft function
*Published: 2026 May 8*
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.
DOI: 10.1016/j.cell.2026.04.024