Principles for integrating reactive species into in vivo biological processes: examples from exercise physiology

Nikos V. Margaritelis, James N. Cobley, Vassilis Paschalis, Aristidis S. Veskoukis, Anastasios A. Theodorou, Antonios Kyparos, Michalis G. Nikolaidis

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)
207 Downloads (Pure)


The equivocal role of reactive species and redox signaling in exercise responses and adaptations is an example clearly showing the inadequacy of current redox biology research to shed light on fundamental biological processes in vivo. Part of the answer probably relies on the extreme complexity of the in vivo redox biology and the limitations of the currently applied methodological and experimental tools. We propose six fundamental principles that should be considered in future studies to mechanistically link reactive species production to exercise responses or adaptations: 1) identify and quantify the reactive species, 2) determine the potential signaling properties of the reactive species, 3) detect the sources of reactive species, 4) locate the domain modified and verify the (ir)reversibility of post-translational modifications, 5) establish causality between redox and physiological measurements, 6) use selective and targeted antioxidants. Fulfilling these principles requires an idealized human experimental setting, which is certainly a utopia. Thus, researchers should choose to satisfy those principles, which, based on scientific evidence, are most critical for their specific research question.
Original languageEnglish
Pages (from-to)256-271
Number of pages16
JournalCellular Signalling
Issue number4
Early online date23 Dec 2015
Publication statusPublished - Apr 2016


  • Free radicals
  • Hydrogen peroxide
  • Oxidative stress
  • Physiology
  • Redox signaling


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