Vitamin K1 inhibits ferroptosis and counteracts a detrimental effect of phenprocoumon in experimental acute kidney injury

• DOI: 10.1007/s00018-022-04416-w
• Publication Date: 2022-06-28T14:03:01Z
• Authors: Benedikt Kolbrink; Friedrich Alexand...; Maja Lucia Messtorff; Theresa Riebeling; Raphael Nische; Jessica Schmitz; Jan Hinrich Bräsen; Ulrich Kunzendorf; Stefan Krautwald
• Keywords: 0303 health sciences; 03 medical and health sciences; Iron; Phenprocoumon; Ferroptosis; Humans; Original Article; Vitamin K 1; Acute Kidney Injury; 3. Good health

Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types death, is characterized by lipid peroxidation, reactive oxygen species production, mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Therefore, become major focus translational research. However, despite its involvement pathological conditions, there are no pharmacologic inhibitors clinical use. In the context drug repurposing, strategy identifying new uses approved drugs outside original medical application, we discovered that vitamin K1 an efficient inhibitor ferroptosis. Our findings strengthened fact K antagonist phenprocoumon significantly exacerbated ferroptotic vitro also massively worsened course injury vivo, which utmost importance. We therefore assign novel role preventing tubular necrosis during Since safety, tolerability, pharmacokinetics, pharmacodynamics formulations well documented, this primed provides pharmacological control diseases associated with mode death.