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Dose-modifying factor for captopril for mitigation of radiation injury to normal lung. J Radiat Res 2012 Jul;53(4):633-40 PMID: 22843631 PMCID: PMC3393339

Pubmed ID

22843631

Abstract

Our goal is to develop countermeasures for pulmonary injury following unpredictable events such as radiological terrorism or nuclear accidents. We have previously demonstrated that captopril, an angiotensin converting enzyme (ACE) inhibitor, is more effective than losartan, an angiotensin type-1 receptor blocker, in mitigating radiation-pneumopathy in a relevant rodent model. In the current study we determined the dose modifying factors (DMFs) of captopril for mitigation of parameters of radiation pneumonitis. We used a whole animal model, irradiating 9-10-week-old female rats derived from a Wistar strain (WAG/RijCmcr) with a single dose of irradiation to the thorax of 11, 12, 13, 14 or 15 Gy. Our study develops methodology to measure DMFs for morbidity (survival) as well as physiological endpoints such as lung function, taking into account attrition due to lethal radiation-induced pneumonitis. Captopril delivered in drinking water (140-180 mg/m(2)/day, comparable with that given clinically) and started one week after irradiation has a DMF of 1.07-1.17 for morbidity up to 80 days (survival) and 1.21-1.35 for tachypnea at 42 days (at the peak of pneumonitis) after a single dose of ionizing radiation (X-rays). These encouraging results advance our goals, since DMF measurements are essential for drug labeling and comparison with other mitigators.

Author List

Medhora M, Gao F, Fish BL, Jacobs ER, Moulder JE, Szabo A

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-s2.0-84872114086   19 Citations

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

Angiotensin-Converting Enzyme Inhibitors
Animals
Captopril
Dose-Response Relationship, Radiation
Female
Humans
Lung
Lung Injury
Proportional Hazards Models
Radiation Injuries
Radiation Pneumonitis
Rats
Rats, Wistar
Respiration
Tachypnea
Time Factors
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6