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

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 Bmitigation^). 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.

Effects of Diet on Late Radiation Injuries in Rats

“…In preparation for studies of the mitigation efficacy of dietary antioxidants we placed rats on this type of diet, specifically a modified version of AIN-76A. In a radiation nephropathy model (Cohen et al 2015) we found that, compared to our standard diet (Teklad 8904), use of the AIN-76A diet after irradiation significantly decreased the incidence and severity of radiation nephropathy. Further studies were then conducted to confirm this unexpected effect, to attempt to determine its mechanistic basis, and to test whether the effect also extended to radiation pneumonitis.…”