Ten “Cheat Codes” for Measuring Oxidative Stress in Humans
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Abstract
Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, oxidative damage, and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code(s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.
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Cites
Sies, H. (2017) · Redox Biology · doi:10.1016/j.redox.2016.12.035 · Cited by 2,148 · see citing works
Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
Egan, B., & Zierath, J. R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.012 · Cited by 2,084 · see citing works
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968 · see citing works
Jones, D. P. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1865 · Cited by 1,726 · see citing works
Cellular Defenses against Superoxide and Hydrogen Peroxide
Imlay, J. A. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061606.161055 · Cited by 1,563 · see citing works
Proteoform: a single term describing protein complexity
The Consortium for Top Down Proteomics, Smith, L. M., & Kelleher, N. L. (2013) · Nature Methods · doi:10.1038/nmeth.2369 · Cited by 1,528 · cited 1× · see citing works
“N -hydroxysuccin-”
Oxidative stress and cancer: Have we moved forward?
Halliwell, B. (2007) · Biochemical Journal · doi:10.1042/bj20061131 · Cited by 1,302 · see citing works
Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine
Radi, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804932115 · Cited by 1,142 · see citing works
Large language models generate functional protein sequences across diverse families
Madani, A., Krause, B., Greene, E. R., Subramanian, S., Mohr, B. P., Holton, J. M., Olmos, J. L., Xiong, C., Sun, Z. Z., Socher, R., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01618-2 · Cited by 1,078 · see citing works
How many human proteoforms are there?
Aebersold, R., Agar, J. N., Amster, I. J., Baker, M. S., Bertozzi, C. R., Boja, E. S., Costello, C. E., Cravatt, B. F., Fenselau, C., Garcia, B. A., et al. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2576 · Cited by 907 · see citing works
Unraveling the biological roles of reactive oxygen species
Murphy, M. P., Holmgren, A., Larsson, N.-G., Halliwell, B., Chang, C. J., Kalyanaraman, B., Rhee, S. G., Thornalley, P. J., Partridge, L., Gems, D., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.010 · Cited by 836 · see citing works
Jones, D. P., & Sies, H. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6247 · Cited by 647 · see citing works
Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I
Chouchani, E. T., Methner, C., Nadtochiy, S. M., Logan, A., Pell, V. R., Ding, S., James, A. M., Cochemé, H. M., Reinhold, J., Lilley, K. S., et al. (2013) · Nature Medicine · doi:10.1038/nm.3212 · Cited by 619 · cited 1× · see citing works
“So far, we have presented cheat codes for measuring oxidative stress by using experimental methods in humans.”
MethodThe wanderings of a free radical
Halliwell, B. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.11.008 · Cited by 467 · see citing works
Antioxidants: Molecules, medicines, and myths
Gutteridge, J. M. C., & Halliwell, B. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.071 · Cited by 405 · see citing works
Goncalves, R. L. S., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M., & Brand, M. D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.619072 · Cited by 329 · cited 1× · see citing works
“As studies comparing rest with exercise attest [27], the dynamic variable rate of mitochondrial superoxide production is context-dependent [28,29].”
BackgroundKeeley, T. P., & Mann, G. E. (2019) · Physiological Reviews · doi:10.1152/physrev.00041.2017 · Cited by 329 · see citing works
Proteoforms as the next proteomics currency
Smith, L. M., & Kelleher, N. L. (2018) · Science · doi:10.1126/science.aat1884 · Cited by 322 · see citing works
Oxygen and Mammalian Cell Culture: Are We Repeating the experiment of Dr. Ox?
Ast, T., & Mootha, V. K. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0105-0 · Cited by 125 · see citing works
4-hydroxynonenal-mediated signaling and aging
Zhang, H., & Forman, H. J. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.11.032 · Cited by 114 · see citing works
Accelerating the search for the missing proteins in the human proteome
Baker, M. S., Ahn, S. B., Mohamedali, A., Islam, M. T., Cantor, D., Verhaert, P. D., Fanayan, S., Sharma, S., Nice, E. C., Connor, M., et al. (2017) · Nature Communications · doi:10.1038/ncomms14271 · Cited by 100 · see citing works
Tyrosine-nitrated proteins: Proteomic and bioanalytical aspects
Batthyány, C., Bartesaghi, S., Mastrogiovanni, M., Lima, A., Demicheli, V., & Radi, R. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6787 · Cited by 86 · see citing works
Carroll, L., Pattison, D. I., Davies, J. B., Anderson, R. F., Lopez-Alarcon, C., & Davies, M. J. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.02.033 · Cited by 48 · see citing works
Cobley, J. N., Margaritelis, N. V., Morton, J. P., Close, G. L., Nikolaidis, M. G., & Malone, J. K. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00182 · Cited by 43 · see citing works
Self-citationZatopek, K. M., Potapov, V., Maduzia, L. L., Alpaslan, E., Chen, L., Evans, T. C., Ong, J. L., Ettwiller, L. M., & Gardner, A. F. (2019) · DNA Repair · doi:10.1016/j.dnarep.2019.06.007 · Cited by 31 · cited 1× · see citing works
“While the redox regulation (see Box 1) literature dates back to at least 1966 [220], with reviews on the subject published in the 1980s [221], the turn of the millennium [222], marked a seismic shift in how the field interpreted exercise-induced oxidative stress [223].”
Background
Flagged first, then by citations
- Authors
- Cobley, J. N., Margaritelis, N. V., Chatzinikolaou, P. N., Nikolaidis, M. G., & Davison, G. W.
- Affiliations
- University of Ulster (GB)
- Aristotle University of Thessaloniki (GR)
- Corresponding author
- Cobley, James N.
- ORCID
- Venue
- Antioxidants
- Publisher
- MDPI AG
- Published
- 2024-07-22
- Volume
- 13
- Issue
- 7
- Pages
- 877
- ISSN
- 2076-3921 (ISSN-L)
- PMC
- PMC11273696
- OpenAlex
- W4400905504
- Cited by
- 17
- References
- 25
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 3
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Antioxidants (publishedVersion, cc-by)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
- Discovery Research Portal (University of Dundee) (submittedVersion, cc-by)
- Ulster University Research Portal (Ulster University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- reactive oxygen species, oxidative damage, redox regulation, lipid peroxidation, TBARS
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