Journal Article

Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome

McCart, Elizabeth A., Slaven, John E., Day, Regina M., Bouten, Roxane M., Du, Yang, Lee, Sang-Ho, Rittase, W. Bradley, Di Pucchio, Tiziana, Wilkins, W. Louis, Gudmundsson, Kristbjorn O., Olsen, Cara H., Mungunsukh, Ognoon, Bylicky, Michelle A., Muir, Jeannie M.

2021

Overview

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 ( 60 Co 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acute Radiation Syndrome - drug therapy / Acute Radiation Syndrome - pathology / Alliances / Amyloid / Angiotensin / Angiotensin-converting enzyme inhibitors / Animal models / Animals / Armed forces / Auroral kilometric radiation / Biology and Life Sciences / Blood / Blood cells / Bone marrow / Cancer therapies / Captopril / Captopril - pharmacology / Care and treatment / Colony-stimulating factor / Complications and side effects / Cytokines / Disease Models, Animal / Drug dosages / Enzyme inhibitors / Erythrocytes / Erythropoietin / Erythropoietin - genetics / Euthanasia / Experiments / FDA approval / Gene expression / Gene Expression Regulation - drug effects / Gene Expression Regulation - radiation effects / Granulocyte-macrophage colony stimulating factor / Granulocyte-Macrophage Colony-Stimulating Factor - genetics / Granulocytes / Health aspects / Health sciences / Hematopoietic System - drug effects / Hematopoietic System - injuries / Hematopoietic System - pathology / Hematopoietic System - radiation effects / Humans / Inflammation / Inflammatory response / Injuries / Irradiation / Laboratory animals / Leukocytes (mononuclear) / Leukocytes, Mononuclear - drug effects / Leukocytes, Mononuclear - radiation effects / Medical research / Medicine and health sciences / Mice / Oxidation-Reduction - drug effects / Pathology / Patient outcomes / Pediatrics / Peptidyl-dipeptidase A / Peripheral blood mononuclear cells / Pharmacology / Platelets / Polymerase chain reaction / Post-irradiation / Preventive medicine / Protein A / Radiation / Radiation effects / Radiation injuries / Radiation Injuries, Experimental - drug therapy / Radiation Injuries, Experimental - pathology / Recovery / Research and Analysis Methods / Semiconductors / Survival / Swine / Swine, Miniature / Whole-Body Irradiation - adverse effects