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

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Abstract

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.

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Author notes

  1. M. Najafi and V. Villa both share the senior authorship.

Authors and Affiliations

  1. School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran

    R. Yahyapour

  2. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    E. Motevaseli

  3. Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    A. Rezaeyan & H. Abdollahi

  4. Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran

    B. Farhood

  5. Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    M. Cheki

  6. Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran

    S. Rezapoor

  7. Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    D. Shabeeb

  8. Department of Physiology, College of Medicine, University of Misan, Amarah, Iraq

    D. Shabeeb

  9. Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran

    A. E. Musa

  10. Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran

    M. Najafi

  11. Scientific Research Department, Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University of Health Sciences (USUHS), Bethesda, MD, 20889-5603, USA

    V. Villa

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Yahyapour, R., Motevaseli, E., Rezaeyan, A. et al. Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clin Transl Oncol 20, 975–988 (2018). https://doi.org/10.1007/s12094-017-1828-6

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