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

Samya Van Coillie, Emily Van San, Ines Goetschalckx, Bartosz Wiernicki, Banibrata Mukhopadhyay, Wulf Tonnus, Sze Men Choi, Ria Roelandt, Catalina Dumitrascu, Ludwig Lamberts, Geert Dams, Wannes Weyts, Jelle Huysentruyt, Behrouz Hassannia, Irina Ingold, Suhas Lele, Evelyne Meyer, Maya Berg, Ruth Seurinck, Yvan Saeys, An Vermeulen, Alexander L. N. van Nuijs, Marcus Conrad, Andreas Linkermann, Mohan Rajapurkar, Peter Vandenabeele, Eric Hoste, Koen Augustyns and Tom Vanden Berghe ()
Additional contact information
Samya Van Coillie: VIB-UGent Center for Inflammation Research
Emily Van San: VIB-UGent Center for Inflammation Research
Ines Goetschalckx: University of Antwerp
Bartosz Wiernicki: VIB-UGent Center for Inflammation Research
Banibrata Mukhopadhyay: Muljibhai Patel Society for Research in Nephro-Urology
Wulf Tonnus: University Hospital Carl Gustav Carus, the Technische Universität Dresden
Sze Men Choi: VIB-UGent Center for Inflammation Research
Ria Roelandt: VIB-UGent Center for Inflammation Research
Catalina Dumitrascu: University of Antwerp
Ludwig Lamberts: University of Antwerp
Geert Dams: University of Antwerp
Wannes Weyts: VIB-UGent Center for Medical Biotechnology
Jelle Huysentruyt: VIB-UGent Center for Inflammation Research
Behrouz Hassannia: VIB-UGent Center for Inflammation Research
Irina Ingold: German Research Center for Environmental Health
Suhas Lele: Muljibhai Patel Society for Research in Nephro-Urology
Evelyne Meyer: Ghent University
Maya Berg: University of Antwerp
Ruth Seurinck: VIB-UGent Center for Inflammation Research
Yvan Saeys: VIB-UGent Center for Inflammation Research
An Vermeulen: Ghent University
Alexander L. N. van Nuijs: University of Antwerp
Marcus Conrad: German Research Center for Environmental Health
Andreas Linkermann: University Hospital Carl Gustav Carus, the Technische Universität Dresden
Mohan Rajapurkar: Muljibhai Patel Society for Research in Nephro-Urology
Peter Vandenabeele: VIB-UGent Center for Inflammation Research
Eric Hoste: Ghent University Hospital; Ghent University
Koen Augustyns: University of Antwerp
Tom Vanden Berghe: VIB-UGent Center for Inflammation Research

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28718-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28718-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28718-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().