Kolbrink, Benedikt;
von Samson-Himmelstjerna, Friedrich Alexander;
Messtorff, Maja Lucia;
Riebeling, Theresa;
Nische, Raphael;
Schmitz, Jessica;
Bräsen, Jan Hinrich;
Kunzendorf, Ulrich;
Krautwald, Stefan
Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury
Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury
Beteiligte:
Kolbrink, Benedikt;
von Samson-Himmelstjerna, Friedrich Alexander;
Messtorff, Maja Lucia;
Riebeling, Theresa;
Nische, Raphael;
Schmitz, Jessica;
Bräsen, Jan Hinrich;
Kunzendorf, Ulrich;
Krautwald, Stefan
Erschienen:
Springer Science and Business Media LLC, 2022
Erschienen in:Cellular and Molecular Life Sciences
Sprache:
Englisch
DOI:
10.1007/s00018-022-04416-w
ISSN:
1420-682X;
1420-9071
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>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. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Therefore, ferroptosis has become a major focus for translational research. However, despite its involvement in pathological conditions, there are no pharmacologic inhibitors of ferroptosis in clinical use. 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. 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. We therefore assign vitamin K1 a novel role in preventing ferroptotic cell death in acute tubular necrosis during acute kidney injury. 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.</jats:p>