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

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 in...

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Autores principales:	W Bradley Rittase, Elizabeth A McCart, Jeannie M Muir, Roxane M Bouten, John E Slaven, Ognoon Mungunsukh, Michelle A Bylicky, W Louis Wilkins, Sang-Ho Lee, Kristbjorn O Gudmundsson, Tiziana Di Pucchio, Cara H Olsen, Yang Du, Regina M Day
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ddb9782493e040cfaf8fd3f494b19c8e
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spelling	oai:doaj.org-article:ddb9782493e040cfaf8fd3f494b19c8e2021-12-02T20:17:31ZEffects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.1932-620310.1371/journal.pone.0256208https://doaj.org/article/ddb9782493e040cfaf8fd3f494b19c8e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256208https://doaj.org/toc/1932-6203Our 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.W Bradley RittaseElizabeth A McCartJeannie M MuirRoxane M BoutenJohn E SlavenOgnoon MungunsukhMichelle A BylickyW Louis WilkinsSang-Ho LeeKristbjorn O GudmundssonTiziana Di PucchioCara H OlsenYang DuRegina M DayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0256208 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q W Bradley Rittase Elizabeth A McCart Jeannie M Muir Roxane M Bouten John E Slaven Ognoon Mungunsukh Michelle A Bylicky W Louis Wilkins Sang-Ho Lee Kristbjorn O Gudmundsson Tiziana Di Pucchio Cara H Olsen Yang Du Regina M Day Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
description	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.
format	article
author	W Bradley Rittase Elizabeth A McCart Jeannie M Muir Roxane M Bouten John E Slaven Ognoon Mungunsukh Michelle A Bylicky W Louis Wilkins Sang-Ho Lee Kristbjorn O Gudmundsson Tiziana Di Pucchio Cara H Olsen Yang Du Regina M Day
author_facet	W Bradley Rittase Elizabeth A McCart Jeannie M Muir Roxane M Bouten John E Slaven Ognoon Mungunsukh Michelle A Bylicky W Louis Wilkins Sang-Ho Lee Kristbjorn O Gudmundsson Tiziana Di Pucchio Cara H Olsen Yang Du Regina M Day
author_sort	W Bradley Rittase
title	Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
title_short	Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
title_full	Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
title_fullStr	Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
title_full_unstemmed	Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.
title_sort	effects of captopril against radiation injuries in the göttingen minipig model of hematopoietic-acute radiation syndrome.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ddb9782493e040cfaf8fd3f494b19c8e
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Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome.

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