Delta Opioid Mediated Radioprotection

  • Brown, Stephen (PI)
  • Oeltgen, Peter (CoI)

Grants and Contracts Details

Description

We have developed a unique deltorphin opioid, Deltorphin-D variant that exhibits radioprotective properties when administered after total body irradiation. Our prior studies have identified deltorphin and opioid activities that are shared with known radioprotective agents. Specifically, selected deltorphins and opioids are protective against endotoxin shock, inhibit caspase activation, inhibit nitric oxide release, induce hibernation, inhibit p38 MAPK activation, are protective in cardiac ischemia/reperfusion injury and confer radioprotection. Thus, the potent anti-oxidative stress and anti-inflammatory properties of deltorphin opioids support our hypothesis that they are a new class of radioprotective agents. Two Aims are proposed. Aim 1 is to optimize Deltorphin-D variant radioprotection in a murine model system. Deltorphin-Dvar will be used to determine the most effective treatment regimen for radioprotection, the dose reduction factor (DRF) and the window of opportunity for radioprotection. Aim 2 is to investigate the mechanism of Deltorphin-D variant opioid mediated radioprotection. This Aim will determine a) the tissue specificity of Deltorphin- 0 variant radioprotection, b) its ability to modulate radiation-induced radioprotective and inflammatory cytokines and growth factors, c) its ability to inhibit radiation-induced intrinsic and extrinsic apoptosis and d) its ability to reduce the number of radiation-induced DNA double-stranded breaks (DSB). This approach to radioprotection may identify a new class of opioid based radioprotective compounds. _-1_-
StatusFinished
Effective start/end date12/1/067/31/08

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.