Back to Search
Start Over
Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
- Source :
-
PloS one [PLoS One] 2021 Aug 27; Vol. 16 (8), pp. e0256208. Date of Electronic Publication: 2021 Aug 27 (Print Publication: 2021). - Publication Year :
- 2021
-
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.<br />Competing Interests: KOG is currently employed by Leidos Biomedical Research Inc. KOG was not employed by Leidos Biomedical Research Inc at the time this study was conducted. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Subjects :
- Acute Radiation Syndrome pathology
Animals
Disease Models, Animal
Erythropoietin genetics
Gene Expression Regulation drug effects
Gene Expression Regulation radiation effects
Granulocyte-Macrophage Colony-Stimulating Factor genetics
Hematopoietic System injuries
Hematopoietic System pathology
Hematopoietic System radiation effects
Humans
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear radiation effects
Mice
Oxidation-Reduction drug effects
Radiation Injuries, Experimental pathology
Swine
Swine, Miniature
Whole-Body Irradiation adverse effects
Acute Radiation Syndrome drug therapy
Captopril pharmacology
Hematopoietic System drug effects
Radiation Injuries, Experimental drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 16
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 34449797
- Full Text :
- https://doi.org/10.1371/journal.pone.0256208