Abstract
Our laboratory has demonstrated that captopril, an angiotensin converting enzyme inhibitor, mitigates hematopoietic injury following total body irradiation in mice. Improved survival in mice is correlated with improved recovery of mature blood cells and bone marrow, reduction of radiation-induced inflammation, and suppression of radiation coagulopathy. Here we investigated the effects of captopril treatment against radiation injuries in the Göttingen mini pig model of Hematopoietic-Acute Radiation Syndrome (H-ARS). Minipigs were given captopril orally (0.96 mg/kg) twice daily for 12 days following total body irradiation (60Co 1.79 Gy, 0.42–0.48 Gy/min). Blood was drawn over a time course following irradiation, and tissue samples were collected at euthanasia (32–35 days post-irradiation). We observed improved survival with captopril treatment, with survival rates of 62.5% in vehicle treated and 87.5% in captopril treated group. Additionally, captopril significantly improved recovery of peripheral blood mononuclear cells, and a trend toward improvement in recovery of red blood cells and platelets. Captopril significantly reduced radiation-induced expression of cytokines erythropoietin and granulocyte-macrophage colony-stimulating factor and suppressed radiation-induced acute-phase inflammatory response cytokine serum amyloid protein A. Using quantitative-RT-PCR to monitor bone marrow recovery, we observed significant suppression of radiation-induced expression of redox stress genes and improved hematopoietic cytokine expression. Our findings suggest that captopril activities in the Göttingen minipig model of hematopoietic-acute radiation syndrome reflect findings in the murine model.
Funder
Defense Medical Research and Development Program
Publisher
Public Library of Science (PLoS)
Reference27 articles.
1. An update on sargramostim for treatment of acute radiation syndrome;VK Singh;Drugs Today (Barc),2018
2. World Nuclear Association (2019) World Nuclear Energy Performance 2019, https://www.world-nuclear.org/getmedia/d77ef8a1-b720-44aa-9b87-abf09f474b43/performance-report-2019.pdf.aspx.
3. Romiplostim (Nplate((R))) as an effective radiation countermeasure to improve survival and platelet recovery in mice;DI Bunin;Int J Radiat Biol,2020
4. Working with the U.S. Food and Drug Administration to obtain approval of products under the Animal Rule;GD Park;Ann N Y Acad Sci,2016
5. Guidance Document. Product Development Under the Animal Rule. Rockville, MD. Food And Drug Administration. 2015 November. Docket Number FDA-2009-D-0007.
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