Antioxidant Approaches to Management of Ionizing Irradiation Injury

Abstract

Ionizing irradiation induces acute and chronic injury to tissues and organs. Applications of antioxidant therapies for the management of ionizing irradiation injury fall into three categories: (1) radiation counter measures against total or partial body irradiation; (2) normal tissue protection against acute organ specific ionizing irradiation injury; and (3) prevention of chronic/late radiation tissue and organ injury. The development of antioxidant therapies to ameliorate ionizing irradiation injury began with initial studies on gene therapy using Manganese Superoxide Dismutase (MnSOD) transgene approaches and evolved into applications of small molecule radiation protectors and mitigators. The understanding of the multiple steps in ionizing radiation-induced cellular, tissue, and organ injury, as well as total body effects is required to optimize the use of antioxidant therapies, and to sequence such approaches with targeted therapies for the multiple steps in the irradiation damage response.

Mechanisms of Normal Tissue Injury From Irradiation

“…Unfortunately, some studies have also failed to show a benefit and have reported allergic reactions 11 . Based on extensive preclinical data supporting SOD gene therapy as a potential therapeutic to prevent radiation injury 12 , alternative methods of SOD delivery, such as an SOD plasmid liposome, have successfully been delivered in Phase I trials 13 . The difficulty in effective and efficient delivery of SOD to irradiated tissue has spurred the development of alternative agents that can act similarly, also known as SOD mimetics.…”

Liquid chromatography–tandem mass spectrometric assay for the quantitation of the novel radiation protective agent and radiation mitigator JP4-039 in murine plasma

“…The oxoammonium cation is highly oxidizing and therefore unlikely to exist for long in biologicals samples if generated [1]. There is strong evidence that JP4-039 can prevent the acute effects of ionizing irradiation and mitigate chronic effects of ionizing irradiation when administered after irradiation [2–8]. Thus, targeted nitroxides such as JP4-039 could be used to protect normal tissue during clinical radiotherapy as well as to serve as a countermeasure to mitigate damage after radiation exposure.…”

“Only a Life Lived for Others Is Worth Living”: Redox Signaling by Oxygenated Phospholipids in Cell Fate Decisions

“…Another enhancing cascade, breach of the intestinal epithelial barrier, designates the transition from ''sterile'' to infectious inflammation, ultimately leading to sepsis and multiple organ failure and thus worsening the overall prognosis and decreasing survival (46,48). In spite of the calamitous nature of radiation inflammatory disease, its sequential development with characteristic phases and dominating cell death pathways gives an encouraging promise for multiple therapeutic approaches within the newly developed concept of precision medicine-accurately timed application of specific regulators targeting selective pathogenic mechanisms and pathways.…”