Hemorrhage Exacerbates Radiation Effects on Survival, Leukocytopenia, Thrombopenia, Erythropenia, Bone Marrow Cell Depletion and Hematopoiesis, and Inflammation-Associated microRNAs Expression in Kidney

• Published in: PloS one Vol. 10; no. 9; p. e0139271
• Main Authors: Kiang, Juliann G, Smith, Joan T, Anderson, Marsha N, Swift, Joshua M, Christensen, Christine L, Gupta, Paridhi, Balakathiresan, Nagaraja, Maheshwari, Radha K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.09.2015; Public Library of Science (PLoS)
• Subjects: Anemia - etiology; Anemia - metabolism; Anesthesia; Animals; Armed forces; Blood; Blood volume; Body Weight; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Bone Marrow Cells - radiation effects; Caspase; Caspase 3 - metabolism; Caspase-3; Cell survival; Complications and side effects; Cytokines - metabolism; Depletion; Disease-Free Survival; Erythropoietin; Erythropoietin - metabolism; Euthanasia; Exposure; Gene expression; Health aspects; Health sciences; Hematopoiesis; Hematopoiesis - radiation effects; Hemorrhage; Hemorrhage - complications; Hemorrhage - mortality; Hemorrhage - pathology; Hypoxia; Ileum; Inflammation; Inflammation - metabolism; Injuries; Interleukin 6; Kidney - blood supply; Kidney - metabolism; Kidney - pathology; Kidney - radiation effects; Kidneys; Laboratory animals; Lethal Dose 50; Leukopenia; Leukopenia - etiology; Life assessment; Male; Mice; MicroRNA; MicroRNAs; MicroRNAs - metabolism; miRNA; Mortality; NF-kappa B - metabolism; Nuclear accidents & safety; Pathology; Physiological aspects; Radiation; Radiation dosage; Radiation effects; Radiation injuries; Radiation Injuries - complications; Radiotherapy; Spleen; Survival; Thrombocytopenia; Thrombocytopenia - etiology; Thrombocytopenia - metabolism; Thrombopenia; Transcription factors; Trauma; Tumor necrosis factor-α; Water - metabolism; γ Radiation; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139271

Exposure to high-dose radiation results in detrimental effects on survival. The effects of combined trauma, such as radiation in combination with hemorrhage, the typical injury of victims exposed to a radiation blast, on survival and hematopoietic effects have yet to be understood. The purpose of this study was to evaluate the effects of radiation injury (RI) combined with hemorrhage (i.e., combined injury, CI) on survival and hematopoietic effects, and to investigate whether hemorrhage (Hemo) enhanced RI-induced mortality and hematopoietic syndrome. Male CD2F1 mice (10 weeks old) were given one single exposure of γ- radiation (60Co) at various doses (0.6 Gy/min). Within 2 hr after RI, animals under anesthesia were bled 0% (Sham) or 20% (Hemo) of total blood volume via the submandibular vein. In these mice, Hemo reduced the LD50/30 for 30-day survival from 9.1 Gy (RI) to 8.75 Gy (CI) with a DMF of 1.046. RI resulted in leukocytopenia, thrombopenia, erythropenia, and bone marrow cell depletion, but decreased the caspase-3 activation response. RI increased IL-1β, IL-6, IL-17A, and TNF-α concentrations in serum, bone marrow, ileum, spleen, and kidney. Some of these adverse alterations were magnified by CI. Erythropoietin production was increased in kidney and blood more after CI than RI. Furthermore, CI altered the global miRNAs expression in kidney and the ingenuity pathway analysis showed that miRNAs viz., let-7e, miR-30e and miR-29b that were associated with hematopoiesis and inflammation. This study provides preliminary evidence that non-lethal Hemo exacerbates RI-induced mortality and cell losses associated with high-dose γ-radiation. We identified some of the initial changes occurring due to CI which may have facilitated in worsening the injury and hampering the recovery of animals ultimately resulting in higher mortality.