Clinical and Translational Oncology

, Volume 20, Issue 8, pp 975–988 | Cite as

Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics

  • R. Yahyapour
  • E. Motevaseli
  • A. Rezaeyan
  • H. Abdollahi
  • B. Farhood
  • M. Cheki
  • S. Rezapoor
  • D. Shabeeb
  • A. E. Musa
  • M. NajafiEmail author
  • V. Villa
Review Article


Every year, millions of cancer patients undergo radiation therapy for treating and destroying abnormal cell growths within normal cell environmental conditions. Thus, ionizing radiation can have positive therapeutic effects on cancer cells as well as post-detrimental effects on surrounding normal tissues. Previous studies in the past years have proposed that the reduction and oxidation metabolism in cells changes in response to ionizing radiation and has a key role in radiation toxicity to normal tissue. Free radicals generated from ionizing radiation result in upregulation of cyclooxygenases (COXs), nitric oxide synthase (NOSs), lipoxygenases (LOXs) as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and their effected changes in mitochondrial functions are markedly noticeable. Each of these enzymes is diversely expressed in multiple cells, tissues and organs in a specific manner. Overproduction of reactive oxygen radicals (ROS), reactive hydroxyl radical (ROH) and reactive nitrogen radicals (RNS) in multiple cellular environments in the affected nucleus, cell membranes, cytosol and mitochondria, and other organelles, can specifically affect the sensitive and modifying enzymes of the redox system and repair proteins that play a pivotal role in both early and late effects of radiation. In recent years, ionizing radiation has been known to affect the redox functions and metabolism of NADPH oxidases (NOXs) as well as having destabilizing and detrimental effects on directly and indirectly affected cells, tissues and organs. More noteworthy, chronic free radical production may continue for years, increasing the risk of carcinogenesis and other oxidative stress-driven degenerative diseases as well as pathologies, in addition to late effect complications of organ fibrosis. Hence, knowledge about the mechanisms of chronic oxidative damage and injury in affected cells, tissues and organs following exposure to ionizing radiation may help in the development of treatment and management strategies of complications associated with radiotherapy (RT) or radiation accident victims. Thus, this medically relevant phenomenon may lead to the discovery of potential antioxidants and inhibitors with promising results in targeting and modulating the ROS/NO-sensitive enzymes in irradiated tissues and organ injury systems.


Radiation Redox Normal tissue injury Inflammation NADPH oxidase 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


All opinions are the personal and professional opinions of the authors and are not the opinions of their respective academic affiliations and agencies. Masoud Najafi and Vilmar Villa share both senior authorship.


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.School of MedicineJiroft University of Medical SciencesJiroftIran
  2. 2.Department of Molecular Medicine, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  3. 3.Department of Medical Physics, School of MedicineIran University of Medical SciencesTehranIran
  4. 4.Departments of Medical Physics and Radiology, Faculty of Paramedical SciencesKashan University of Medical SciencesKashanIran
  5. 5.Department of Radiologic Technology, Faculty of ParamedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
  6. 6.Department of Radiology, Faculty of ParamedicalTehran University of Medical SciencesTehranIran
  7. 7.Department of Medical Physics and Biomedical Engineering, Faculty of MedicineTehran University of Medical SciencesTehranIran
  8. 8.Department of Physiology, College of MedicineUniversity of MisanAmarahIraq
  9. 9.Research Center for Molecular and Cellular ImagingTehran University of Medical SciencesTehranIran
  10. 10.Radiology and Nuclear Medicine Department, School of Paramedical SciencesKermanshah University of Medical ScienceKermanshahIran
  11. 11.Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI)Uniformed Services University of Health Sciences (USUHS)BethesdaUSA

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