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Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo

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Murphy, Michael P., Bayir, Hülya, Belousov, Vsevolod, Chang, Christopher J., Davies, Kelvin J. A., Davies, Michael J., Dick, Tobias P., Finkel, Toren +17 more·2022·Nature Metabolism
DOI 10.1038/s42255-022-00591-zPMC PMC9711940
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Abstract

Multiple roles of reactive oxygen species (ROS) and their consequences for health and disease are emerging throughout biological sciences. This development has led researchers unfamiliar with the complexities of ROS and their reactions to employ commercial kits and probes to measure ROS and oxidative damage inappropriately, treating ROS (a generic abbreviation) as if it were a discrete molecular entity. Unfortunately, the application and interpretation of these measurements are fraught with challenges and limitations. This can lead to misleading claims entering the literature and impeding progress, despite a well-established body of knowledge on how best to assess individual ROS, their reactions, role as signalling molecules and the oxidative damage that they can cause. In this consensus statement we illuminate problems that can arise with many commonly used approaches for measurement of ROS and oxidative damage, and propose guidelines for best practice. We hope that these strategies will be useful to those who find their research requiring assessment of ROS, oxidative damage and redox signalling in cells and in vivo.

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  • The DCF readout is an indicator of total reactive species levels (ROS/NOS) in tissues.

    “The DCF readout of the samples was used as an indicator of the total reactive species levels (ROS/NOS) present in the tissues.”

    From Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice (2026) · cites this paper as [36]

    The ‘Guidelines and limitations of the detection and measurement of ROS’ section (page not provided) says DCFH can be oxidized to fluorescent DCF by several ROS, supporting its use as a nonspecific signal. But it restricts the readout to an initial assessment of changes in cellular redox state and warns that fluorescence may not increase linearly with ROS. It does not support interpreting DCF as a measure of total ROS/NOS levels in tissues. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

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Authors
Murphy, M. P., Bayir, H., Belousov, V., Chang, C. J., Davies, K. J. A., Davies, M. J., Dick, T. P., Finkel, T., Forman, H. J., Janssen-Heininger, Y., Gems, D., Kagan, V. E., Kalyanaraman, B., Larsson, N.-G., Milne, G. L., Nyström, T., Poulsen, H. E., Radi, R., Van Remmen, H., Schumacker, P. T., Thornalley, P. J., Toyokuni, S., Winterbourn, C. C., Yin, H., & Halliwell, B.
Affiliations
  • University of Cambridge (GB)
  • University of California, Berkeley (US)
  • University of Southern California (US)
  • University of Copenhagen (DK)
  • German Cancer Research Center (DE)
  • University of Pittsburgh (US)
  • University College London (GB)
  • University of Vermont (US)
  • Medical College of Wisconsin (US)
  • Karolinska Institutet (SE)
  • Vanderbilt University Medical Center (US)
  • University of Gothenburg (SE)
  • Copenhagen University Hospital (DK)
  • Northwestern University (US)
  • Hamad bin Khalifa University (QA)
  • Nagoya University (JP)
  • University of Otago (NZ)
  • Chinese Academy of Sciences (CN)
  • National University of Singapore (SG)
Corresponding author
  • Murphy, Michael P.
  • Halliwell, Barry
ORCID
Venue
Nature Metabolism
Publisher
Springer Science and Business Media LLC
Published
2022-06-27
Volume
4
Issue
6
Pages
651-662
ISSN
2522-5812 (ISSN-L)
DOI
10.1038/s42255-022-00591-z
PMC
PMC9711940
OpenAlex
W4283701282
Cited by
1,514
References
5
Citations by year
2026: 442 · 2025: 413 · 2024: 381 · 2023: 238 · 2022: 39 · 2017: 1
FWCI
87.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion)
  • Apollo
Funders
  • U.S. Department of Veterans Affairs (IK6BX005234)
  • Canadian Institute for Advanced Research
  • Wellcome Trust (220257/Z/20/Z, 220257)
  • Swedish Cancer Foundation
  • National Research Foundation
  • National University of Singapore
  • National Research Foundation Singapore
  • Deutsche Forschungsgemeinschaft (SPP2306)
  • National Natural Science Foundation of China (32150710522, 32030053)
  • Knut och Alice Wallenbergs Stiftelse
  • Novo Nordisk (NNF13OC0004294)
  • Vetenskapsrådet (2015-00418)
  • Universidad de la República Uruguay (CSIC_2018, EI_2020)
  • Princess Takamatsu Cancer Research Fund (19-25126, JP16H06276)
  • Novo Nordisk Fonden (NNF19OC0058493, NNF13OC0004294, NNF 20SA0064214)
  • National Institutes of Health (79465, ES003598, HL114453, NS061817)
  • Medical Research Council (220257/Z/20/Z, MC_UU_00015/3)
  • National Medical Research Council
  • Japan Society for the Promotion of Science (JP20H05502, JP19H05462 and JP20H05502, 742039, JPMJCR19H4, 19H05462, CREST, #JP16H06276)
  • National Institute on Aging (# AG052374, ES003598, T32AG052374)
  • National Heart, Lung, and Blood Institute (R35HL135828, P01HL114453)
  • National Cancer Institute (R01CA165065, R01CA266342)
  • National Institute of General Medical Sciences (R01GM139245, R01GM079465)
  • National Institute of Allergy and Infectious Diseases (U01AI156924, U01AI156923, R01AI145406)
  • National Institute of Neurological Disorders and Stroke (R01NS061817, R01NS117000, R37NS061817, R01NS076511)
  • National Institute of Environmental Health Sciences (R56ES003598, ES28096, #ES003598, R01ES003598, 28096, R01ES028096)
  • Core Research for Evolutional Science and Technology (JP19H05462, JPMJCR19H4, JP20H05502)
  • H2020 European Research Council (741366)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
reactive oxygen species, oxidative damage, redox signaling, oxidation, measurement guidelines, cell-based assays
MeSH terms
Antioxidants, Oxidation-Reduction, Signal Transduction, Reactive Oxygen Species, Oxidative Stress

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