Novel Tissue Protective Agents for the Treatment of Acute Radiation- induced BMF.

摘要

The threat of terrorist attacks involving radioactive material mandates the study and development of potential new treatments for bone marrow failure caused by acute radiation injury. A whole body dose of radiation even at levels as low as 1Gy can result in Bone Marrow Failure. Hematopoietic Acute Radiation Syndrome is characterized by bone marrow failure with life threatening neutropenia and thrombocytopenia. In addition to direct injury to hematopoietic cells, radiation is known to induce a pro-inflammatory cytokine storm in which various cell types produce cytokines, chemokines, growth factors and reactive oxygen species that can be especially detrimental to hematopoietic stem cells. Inflammation and oxidative damage induced by radiation exposure are significant contributors to bone marrow failure. We and our collaborators have recently shown that a short EPO-mimetic peptide improves survival in a murine model of acute radiation induced Bone Marrow Failure, however the peptide s molecular mechanism is unknown. The specific hypothesis behind the proposed research project is that the EPO- mimetic peptide decreases the mortality rate in a mouse model of radiation induced Bone Marrow Failure by directly inhibiting apoptosis in hematopoietic stem cells.