Salen Manganese Complexes Mitigate Radiation Injury in Normal Tissues Through Modulation of Tissue Environment, Including Through Redox Mechanisms

Abstract

There is a need for therapeutic agents to reduce injury to normal tissues that can occur as a delayed consequence of not only radiation therapy, but also an accidental or terrorism-associated radiation exposure. While the mechanisms of delayed radia- tion injury are not well understood, there is evidence suggesting that oxidative stress is involved. Therefore, we and others have studied synthetic agents that scav- enge reactive oxygen species (ROS) such as superoxide and hydrogen peroxide as potential therapeutic agents to mitigate normal tissue injury resulting from ion- izing radiation. A wide range of antioxidant strategies has been studied for mitiga- tion of radiation-induced normal tissue injury, including: nutraceutical, free-radical scavengers, superoxide dismutase (SOD) mimetics, fl avones, mitochondrial-targeted nitroxides , iron chelators, NADPH oxidase inhibitors, and Mn porphyrins. This review focuses primarily on radia- tion mitigation studies employing one class of synthetic ROS scavenger, synthetic metal-containing compounds known as salen Mn complexes.