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Tschuck, J. ; Tonnus, W.* ; Gavali, S.* ; Kolak, A. ; Mallais, M.* ; Maremonti, F.* ; Sato, M.* ; Rothenaigner, I. ; Friedmann Angeli, J.P.* ; Pratt, D.A.* ; Linkermann, A.* ; Hadian, K.

Seratrodast inhibits ferroptosis by suppressing lipid peroxidation.

Cell Death Dis. 15:853 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Ferroptosis is a regulated and non-apoptotic form of cell death mediated by iron-dependent peroxidation of polyunsaturated fatty acyl tails in phospholipids. Research of the past years has shed light on the occurrence of ferroptosis in organ injury and degenerative diseases of the brain, kidney, heart, and other tissues. Hence, ferroptosis inhibition may prove therapeutically beneficial to treat distinct diseases. In this study, we explored the ferroptosis-modulating activity of seratrodast, an inhibitor of thromboxane A2 (TXA2) receptor, which is approved in some countries for the treatment of asthma. Interestingly, seratrodast suppressed ferroptosis, but not apoptosis and necroptosis; thus, demonstrating selective anti-ferroptotic activity. While seratrodast itself does not inhibit lipid peroxidation, it exhibits potent radical-trapping antioxidant activity upon reduction to its corresponding hydroquinone form-analogously to ubiquinone and vitamin K. Importantly, seratrodast ameliorated the severity of renal ischemia-reperfusion injury in mice. Together, this study provides a drug repurposing case, where seratrodast-a marketed drug-can undergo fast-forward preclinical/clinical development for the inhibition of ferroptosis in distinct degenerative diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cell-death; Reactivity; Mechanisms
ISSN (print) / ISBN 2041-4889
e-ISSN 2041-4889
Zeitschrift Cell Death & Disease
Quellenangaben Band: 15, Heft: 11, Seiten: , Artikelnummer: 853 Supplement: ,
Verlag Nature Publishing Group
Verlagsort Campus, 4 Crinan St, London, N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
Förderungen Helmholtz Munich
Projekt DEAL
natural sciences and engineering research council of canada