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

Samya Van Coillie (UGent) , Emily Van San (UGent) , Ines Goetschalckx, Bartosz Wiernicki (UGent) , Banibrata Mukhopadhyay, Wulf Tonnus, Sze Men Choi (UGent) , Ria Roelandt (UGent) , Catalina Dumitrascu, Ludwig Lamberts, et al.
(2022) NATURE COMMUNICATIONS. 13(1).
Author
Organization
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.
Keywords
General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, GLUTATHIONE-PEROXIDASE 4, PLASMA CATALYTIC IRON, CELL-DEATH, ANTIOXIDANT STATUS, OXIDATIVE STRESS, RENAL-FAILURE, MICE, GLUTATHIONE-PEROXIDASE-4, REGULATOR, MORTALITY

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MLA
Van Coillie, Samya, et al. “Targeting Ferroptosis Protects against Experimental (Multi)Organ Dysfunction and Death.” NATURE COMMUNICATIONS, vol. 13, no. 1, 2022, doi:10.1038/s41467-022-28718-6.
APA
Van Coillie, S., Van San, E., Goetschalckx, I., Wiernicki, B., Mukhopadhyay, B., Tonnus, W., … Vanden Berghe, T. (2022). Targeting ferroptosis protects against experimental (multi)organ dysfunction and death. NATURE COMMUNICATIONS, 13(1). https://doi.org/10.1038/s41467-022-28718-6
Chicago author-date
Van Coillie, Samya, Emily Van San, Ines Goetschalckx, Bartosz Wiernicki, Banibrata Mukhopadhyay, Wulf Tonnus, Sze Men Choi, et al. 2022. “Targeting Ferroptosis Protects against Experimental (Multi)Organ Dysfunction and Death.” NATURE COMMUNICATIONS 13 (1). https://doi.org/10.1038/s41467-022-28718-6.
Chicago author-date (all authors)
Van Coillie, Samya, 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. 2022. “Targeting Ferroptosis Protects against Experimental (Multi)Organ Dysfunction and Death.” NATURE COMMUNICATIONS 13 (1). doi:10.1038/s41467-022-28718-6.
Vancouver
1.
Van Coillie S, Van San E, Goetschalckx I, Wiernicki B, Mukhopadhyay B, Tonnus W, et al. Targeting ferroptosis protects against experimental (multi)organ dysfunction and death. NATURE COMMUNICATIONS. 2022;13(1).
IEEE
[1]
S. Van Coillie et al., “Targeting ferroptosis protects against experimental (multi)organ dysfunction and death,” NATURE COMMUNICATIONS, vol. 13, no. 1, 2022.
@article{8743037,
  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.}},
  articleno    = {{1046}},
  author       = {{Van Coillie, Samya and Van San, Emily and Goetschalckx, Ines and Wiernicki, Bartosz and Mukhopadhyay, Banibrata and Tonnus, Wulf and Choi, Sze Men and Roelandt, Ria and Dumitrascu, Catalina and Lamberts, Ludwig and Dams, Geert and Weyts, Wannes and Huysentruyt, Jelle and Hassannia, Behrouz and Ingold, Irina and Lele, Suhas and Meyer, Evelyne and Berg, Maya and Seurinck, Ruth and Saeys, Yvan and Vermeulen, An and van Nuijs, Alexander L. N. and Conrad, Marcus and Linkermann, Andreas and Rajapurkar, Mohan and Vandenabeele, Peter and Hoste, Eric and Augustyns, Koen and Vanden Berghe, Tom}},
  issn         = {{2041-1723}},
  journal      = {{NATURE COMMUNICATIONS}},
  keywords     = {{General Physics and Astronomy,General Biochemistry,Genetics and Molecular Biology,General Chemistry,GLUTATHIONE-PEROXIDASE 4,PLASMA CATALYTIC IRON,CELL-DEATH,ANTIOXIDANT STATUS,OXIDATIVE STRESS,RENAL-FAILURE,MICE,GLUTATHIONE-PEROXIDASE-4,REGULATOR,MORTALITY}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{14}},
  title        = {{Targeting ferroptosis protects against experimental (multi)organ dysfunction and death}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-28718-6}},
  volume       = {{13}},
  year         = {{2022}},
}
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