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Enalapril mitigates focal alveolar lesions, a histological marker of late pulmonary injury by radiation to the lung. Radiat Res 2013 Apr;179(4):465-74 PMID: 23480564 PMCID: PMC3697111

Pubmed ID

23480564

Abstract

The goal of our study was to identify a histological marker for testing countermeasures for mitigation of late radiation injury to the lung. Pulmonary fibrosis is currently the best described "late effect" in survivors of acute radiation pneumonitis. However, robust fibrosis does not develop in some rodent strains for years after a single dose of radiation to the whole thorax. We observed radiation-associated focal alveolar lesions that were rich in giant cells and macrophages containing cholesterol clefts in the lungs of irradiated WAG/RijCmcr rats. These lesions were first observed after pneumonitis, around 21 weeks after receiving a radiation dose of 13 Gy to the thorax but not until 71 weeks in unirradiated rats. The number of cholesterol clefts increased with time after irradiation through 64 weeks of observation, and at 30 weeks after 13 Gy, cholesterol clefts were associated with several indices of deterioration in lung function. The number of cholesterol clefts in irradiated lung sections were reduced by the angiotensin converting enzyme (ACE) inhibitor enalapril (25-42 mg/m²/day) from 18.7 ± 4.2/lung section to 6.8 ± 2.4 (P = 0.029), 5.2 ± 1.9 (P = 0.0051) and 6.7 ± 1.9 (P = 0.029) when the drug was started at 1 week, 5 or 15 weeks after irradiation, respectively, and continued. Similar lesions have been previously observed in the lungs of one strain of irradiated mice and in patients following radiotherapy. We propose that alveolar lesions with cholesterol clefts may be used as a histological marker of the severity of radiation lung injury and to study its mitigation in WAG/RijCmcr rats.

Author List

Gao F, Narayanan J, Joneikis C, Fish BL, Szabo A, Moulder JE, Molthen RC, Jacobs ER, Rao RN, Medhora M

Authors

Elizabeth R. Jacobs MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin
Meetha M. Medhora PhD Professor in the Radiation Oncology department at Medical College of Wisconsin
Aniko Szabo PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-84876241819   8 Citations

MESH terms used to index this publication - Major topics in bold

Angiotensin-Converting Enzyme Inhibitors
Animals
Antigens, CD
Antigens, Differentiation, Myelomonocytic
Cholesterol
Enalapril
Female
Immunohistochemistry
Lung
Lung Injury
Peroxidase
Pulmonary Alveoli
Radiation Injuries
Rats
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6