![]() ![]() First recognized as a distinct entity in 2008, and named in 2012, ferroptosis is a form of inflammatory cell death, characterized by excessive iron-dependent lipid peroxidation in the plasma membrane. In recent years, it has become evident that the cell death form ferroptosis is the most pathophysiologically relevant form of cell death in acute tubular necrosis during AKI. Despite major scientific efforts, there is currently no established therapy that can halt pathological cell death in the kidney, as it occurs during acute tubular necrosis in AKI. Therapy for AKI currently consists of supportive measures in addition to removal of trigger factors. Since the safety, tolerability, pharmacokinetics, and pharmacodynamics of vitamin K1 formulations are well documented, this drug is primed for clinical application, and provides a new strategy for pharmacological control of ferroptosis and diseases associated with this mode of cell death.Īcute kidney injury (AKI) occurs in up to 20% of hospitalized patients and is a major clinical problem that is associated with high mortality and morbidity. We therefore assign vitamin K1 a novel role in preventing ferroptotic cell death in acute tubular necrosis during acute kidney injury. Our findings are strengthened by the fact that the vitamin K antagonist phenprocoumon significantly exacerbated ferroptotic cell death in vitro and also massively worsened the course of acute kidney injury in vivo, which is of utmost clinical importance. In the context of drug repurposing, a strategy for identifying new uses for approved drugs outside the original medical application, we discovered that vitamin K1 is an efficient inhibitor of ferroptosis. ![]() However, despite its involvement in pathological conditions, there are no pharmacologic inhibitors of ferroptosis in clinical use. Therefore, ferroptosis has become a major focus for translational research. ![]() ![]() Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types of cell death, is characterized by lipid peroxidation, reactive oxygen species production, and mitochondrial dysfunction. ![]()
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