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Mitigation of normal tissue radiation injury: evidence from rat radiation nephropathy models

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  • Published:
Journal of Radiation Oncology

Abstract

Normal tissue radiation injury is a common complication of radiation therapy and is also a major concern after accidental or belligerent radiation exposure, and until recently, it was deemed untreatable. Both experimental and clinical evidence now show that radiation injury can be alleviated by agents started after irradiation but before manifestation of that injury (a therapeutic approach called “mitigation”). Mitigation of normal tissue injuries would improve clinical radiation therapy, and it will be an essential medical countermeasure for accidental or belligerent radiation exposures. In rat radiation nephropathy models over 30 potential mitigators have been tested, some (e.g., angiotensin converting enzyme inhibitors and angiotensin II receptor blockers) have been found to be quite effective, but many others appear ineffective, and a few have actually made injury worse. For the most part, work with the successful agents, and the agents that made radiation injury worse, is in the peer-reviewed literature. However, we have found it difficult to publish information on the agents that were ineffective, although we suspect that others have tried some of the same agents and also found them ineffective. Here, we review all agents we know of that have been tested to date in rat radiation nephropathy models, with the goal of helping to prevent needless duplication of studies.

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Funding

These studies were supported by the Department of Veterans Affairs Office of Research and Development, by the Department of Veterans Affairs Merit Review grants to EPC, and by the National Institutes of Health grants CA24652 and AI067734 to JEM.

Conflict of interests

EPC, JEM, and BLF have no conflict of interests. JDI has patents and patent applications that cover the composition of matter for EET analogs.

Research involving animals

Although this is a review article, some previously unpublished animal studies are referenced. Nevertheless, all animal studies have been approved by the appropriate Animal Care and Use Committee, and all institutional and national guidelines for the care and use of laboratory animals were followed.

Research involving humans

Statement of informed consent was not applicable since the manuscript does not contain any patient data, although it does refer to the conclusions of previously published human data.

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Authors and Affiliations

  1. Nephrology Section, University of Maryland, Baltimore Veterans Administration Medical Center, Baltimore, MD, USA

    Eric P. Cohen

  2. Department of Radiation Oncology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA

    Brian L. Fish & John E. Moulder

  3. Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI, USA

    John D. Imig

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  1. Eric P. Cohen
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  2. Brian L. Fish
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  3. John D. Imig
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  4. John E. Moulder
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Correspondence to John E. Moulder.

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Cohen, E.P., Fish, B.L., Imig, J.D. et al. Mitigation of normal tissue radiation injury: evidence from rat radiation nephropathy models. J Radiat Oncol 5, 1–8 (2016). https://doi.org/10.1007/s13566-015-0222-7

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  • DOI: https://doi.org/10.1007/s13566-015-0222-7

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