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.
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Status | Finished |
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Effective start/end date | 12/1/06 → 7/31/08 |
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