The overall goal of this project is to develop a new strategy to protect, ameliorate and treat radiation induced normal tissue injury by using novel synthetic manganese (Mn)-porphyrin mimetics of superoxide dismutase (SOD) as potent scavengers of reactive oxygen species (ROS). The strategy is based on: a) our current mechanistic studies implicating chronic oxidative stress as an important contributing factor in the development of radiation-induced normal tissue injury (NIH grant RO1 CA 098452, P.I. Z Vujaskovic), and b) our established expertise and experience in developing and testing catalytic Mn-porphyrin mimetics of SOD (NIH SBIR grant Aeolus / Duke).

 

This proposal is designed to test two already established Mn porphyrins and further develop, optimize and test three new catalytic Mn-porphyrin compounds and to document their ability to prevent/ameliorate or treat radiation-induced lung tissue injury after accidental or deliberate exposure to ionizing radiation. With the growing threats from radiation exposure as a result of terrorist attack, the development of effective radioprotective compounds as proposed in this project will be an important contribution for the establishment of effective medical countermeasures against radiation. The project is specifically focusing on pulmonary toxicity shown to be potentially fatal in radiation exposure victims who were able to overcome hematopoietic and gastrointestinal syndromes.