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Van Coillie, S.* ; Van San, E.* ; Goetschalckx, I.* ; Wiernicki, B.* ; Mukhopadhyay, B.* ; Tonnus, W.* ; Choi, S.M.* ; Roelandt, R.* ; Dumitrascu, C.* ; Lamberts, L.E.* ; Dams, G.* ; Weyts, W.* ; Huysentruyt, J.* ; Hassannia, B.* ; Ingold, I. ; Lele, S.* ; Meyer, E.* ; Berg, M.* ; Seurinck, R.* ; Saeys, Y.* ; Vermeulen, A.* ; van Nuijs, A.L.N.* ; Conrad, M. ; Linkermann, A.* ; Rajapurkar, M.* ; Vandenabeele, P.* ; Hoste, E.* ; Augustyns, K.* ; Vanden Berghe, T.*

Targeting ferroptosis protects against experimental (multi)organ dysfunction and death.

Nat. Commun. 13:1046 (2022)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
The most common cause of death in the intensive care unit (ICU) is the development of multiorgan dysfunction syndrome (MODS). Besides life-supporting treatments, no cure exists, and its mechanisms are still poorly understood. Catalytic iron is associated with ICU mortality and is known to cause free radical-mediated cellular toxicity. It is thought to induce excessive lipid peroxidation, the main characteristic of an iron-dependent type of cell death conceptualized as ferroptosis. Here we show that the severity of multiorgan dysfunction and the probability of death are indeed associated with plasma catalytic iron and lipid peroxidation. Transgenic approaches underscore the role of ferroptosis in iron-induced multiorgan dysfunction. Blocking lipid peroxidation with our highly soluble ferrostatin-analogue protects mice from injury and death in experimental non-septic multiorgan dysfunction, but not in sepsis-induced multiorgan dysfunction. The limitations of the experimental mice models to mimic the complexity of clinical MODS warrant further preclinical testing. In conclusion, our data suggest ferroptosis targeting as possible treatment option for a stratifiable subset of MODS patients.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 13, Issue: 1, Pages: , Article Number: 1046 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Grants German Research Foundation (DFG)
German Federal Ministry of Education and Research VIP+program
Ministry of Science and Higher Education of The Russian Federation
European Research Council (ERC)
FWO
Strategic Basic Research Foundation Flanders, IRONIX
Methusalem
Flemish Institute of Biotechnology VIB
FWO-SBO
iBOF20/IBF/039 ATLANTIS
VLIRUOS
Charcot Foundation
Foundation against cancer
UGent Special research fund
Industrial Research Fund from Ghent University
Industrial research Fund from University of Antwerp
Consortium of excellence at University of Antwerp INFLA-MED
EOS INFLADIS
Excellence of Science MODEL-IDI