Ghrelin therapy improves survival after whole-body ionizing irradiation or combined with burn or wound: amelioration of leukocytopenia, thrombocytopenia, splenomegaly, and bone marrow injury.
Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to (60)Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA ; Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA ; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Juliann G
JG
Kiang
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
Min
M
Zhai
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
Pei-Jyun
PJ
Liao
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
Thomas B
TB
Elliott
Radiation Combined Injury Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889, USA.
Nikolai V
NV
Gorbunov
D000818:Animals; D002056:Burns / Q000097:blood / Q000188:drug therapy*; D003037:Cobalt Radioisotopes; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D054439:Ghrelin / Q000494:pharmacology*; D007970:Leukopenia / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000097:blood* / Q000188:drug therapy*; D011897:Random Allocation; D013163:Splenomegaly / Q000188:drug therapy / Q000209:etiology; D013921:Thrombocytopenia / Q000188:drug therapy / Q000209:etiology; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects; D014947:Wounds and Injuries / Q000097:blood* / Q000188:drug therapy*
D003037:Cobalt Radioisotopes; D054439:Ghrelin