Enalapril Mitigates Focal Alveolar Lesions, a Histological Marker of Late Pulmonary Injury by Radiation to the Lung

Authors

Feng Gao, Medical College of Wisconsin
Jayashree Narayanan, Medical College of Wisconsin
Cortney Joneikis, Medical College of Wisconsin
Brian L. Fish, Medical College of Wisconsin
Aniko Szabo, Medical College of Wisconsin
John E. Moulder, Medical College of Wisconsin
Robert C. Molthen, Marquette UniversityFollow
Elizabeth R. Jacobs, Medical College of Wisconsin
R. Nagarjun Rao, Medical College of Wisconsin
Meetha Medhora, Medical College of Wisconsin

Document Type

Article

Language

eng

Publication Date

4-2013

Publisher

Radiation Research Society

Source Publication

Radiation Research

Source ISSN

0033-7587

Original Item ID

DOI: 10.1667/RR3127.1

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.

Comments

Radiation Research, Vol. 179, No. 4 (April 2013): 465-474. DOI.

Recommended Citation

Gao, Feng; Narayanan, Jayashree; Joneikis, Cortney; Fish, Brian L.; Szabo, Aniko; Moulder, John E.; Molthen, Robert C.; Jacobs, Elizabeth R.; Rao, R. Nagarjun; and Medhora, Meetha, "Enalapril Mitigates Focal Alveolar Lesions, a Histological Marker of Late Pulmonary Injury by Radiation to the Lung" (2013). Biomedical Engineering Faculty Research and Publications. 118.
https://epublications.marquette.edu/bioengin_fac/118