Personalized redox medicine in inflammatory bowel diseases: an emerging role for HIF-1 alpha and NRF2 as therapeutic targets: an emerging role for HIF-1α and NRF2 as therapeutic targets
Personalized redox medicine in inflammatory bowel diseases: an emerging role for HIF-1 alpha and NRF2 as therapeutic targets: an emerging role for HIF-1α and NRF2 as therapeutic targets
Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are intimately associated with inflammation and overproduction of reactive oxygen species (ROS). Temporal and inter-individual variabilities in disease activity and response to therapy pose significant challenges to diagnosis and patient care. Discovery and validation of truly integrative biomarkers would benefit from embracing redox metabolomics approaches with prioritization of central regulatory hubs. We here make a case for applying a personalized redox medicine approach that aims to selectively inhibit pathological overproduction and/or altered expression of specific enzymatic sources of ROS without compromising physiological function. To this end, improved 'clinical-omics integration' may help to better understand which particular redox signaling pathways are disrupted in what patient. Pharmacological interventions capable of activating endogenous antioxidant defense systems may represent viable therapeutic options to restore local/systemic redox status, with HIF-1α and NRF2 holding particular promise in this context. Achieving the implementation of clinically meaningful mechanism-based biomarkers requires development of easy-to-use, robust and cost-effective tools for secure diagnosis and monitoring of treatment efficacy. Ultimately, matching redox-directed pharmacological interventions to individual patient phenotypes using predictive biomarkers may offer new opportunities to break the therapeutic ceiling in IBD.
Biomarkers/metabolism, Humans, Inflammatory Bowel Diseases/drug therapy, NF-E2-Related Factor 2/genetics, Oxidation-Reduction, Reactive Oxygen Species/metabolism, Inflammatory bowel disease, Oxidative stress, NRF2, Redox medicine, HIF-1α
Bourgonje, Arno R
115e3b3a-f1b0-4d6f-ace1-8329514fa17a
Kloska, Damian
cbae5732-28d9-4c11-ab0a-03260708e903
Grochot-Przęczek, Anna
d5c39354-ed8a-4795-9dda-7b532bc0e8df
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Cuadrado, Antonio
6e8f853a-598d-459c-baba-9ceb8b49a324
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
1 April 2023
Bourgonje, Arno R
115e3b3a-f1b0-4d6f-ace1-8329514fa17a
Kloska, Damian
cbae5732-28d9-4c11-ab0a-03260708e903
Grochot-Przęczek, Anna
d5c39354-ed8a-4795-9dda-7b532bc0e8df
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Cuadrado, Antonio
6e8f853a-598d-459c-baba-9ceb8b49a324
van Goor, Harry
6e4f96a5-c749-43b6-a488-6af71f932dc3
Bourgonje, Arno R, Kloska, Damian, Grochot-Przęczek, Anna, Feelisch, Martin, Cuadrado, Antonio and van Goor, Harry
(2023)
Personalized redox medicine in inflammatory bowel diseases: an emerging role for HIF-1 alpha and NRF2 as therapeutic targets: an emerging role for HIF-1α and NRF2 as therapeutic targets.
Redox Biology, 60, [102603].
(doi:10.1016/j.redox.2023.102603).
Abstract
Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are intimately associated with inflammation and overproduction of reactive oxygen species (ROS). Temporal and inter-individual variabilities in disease activity and response to therapy pose significant challenges to diagnosis and patient care. Discovery and validation of truly integrative biomarkers would benefit from embracing redox metabolomics approaches with prioritization of central regulatory hubs. We here make a case for applying a personalized redox medicine approach that aims to selectively inhibit pathological overproduction and/or altered expression of specific enzymatic sources of ROS without compromising physiological function. To this end, improved 'clinical-omics integration' may help to better understand which particular redox signaling pathways are disrupted in what patient. Pharmacological interventions capable of activating endogenous antioxidant defense systems may represent viable therapeutic options to restore local/systemic redox status, with HIF-1α and NRF2 holding particular promise in this context. Achieving the implementation of clinically meaningful mechanism-based biomarkers requires development of easy-to-use, robust and cost-effective tools for secure diagnosis and monitoring of treatment efficacy. Ultimately, matching redox-directed pharmacological interventions to individual patient phenotypes using predictive biomarkers may offer new opportunities to break the therapeutic ceiling in IBD.
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More information
e-pub ahead of print date: 10 January 2023
Published date: 1 April 2023
Additional Information:
Funding Information:
All authors would like to express their gratitude toward scientific and medical illustrator Nikola Kolundzic (King's College London, UK) for his valuable help in the graphical design of the figures. ARB, AGP, AC and HvG are members of the COST (European Cooperation in Science and Technology) Action CA20121 (Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases, BenBedPhar).
Publisher Copyright:
© 2023 The Authors
Keywords:
Biomarkers/metabolism, Humans, Inflammatory Bowel Diseases/drug therapy, NF-E2-Related Factor 2/genetics, Oxidation-Reduction, Reactive Oxygen Species/metabolism, Inflammatory bowel disease, Oxidative stress, NRF2, Redox medicine, HIF-1α
Identifiers
Local EPrints ID: 475949
URI: http://eprints.soton.ac.uk/id/eprint/475949
ISSN: 2213-2317
PURE UUID: 6b660921-17d5-4663-af7b-27531f8822e5
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Date deposited: 31 Mar 2023 16:51
Last modified: 17 Mar 2024 03:27
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Contributors
Author:
Arno R Bourgonje
Author:
Damian Kloska
Author:
Anna Grochot-Przęczek
Author:
Antonio Cuadrado
Author:
Harry van Goor
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