Renin-Angiotensin System Suppression Mitigates Experimental Radiation Pneumonitis

Abstract

Purpose To find mitigators of pneumonitis induced by moderate doses of thoracic radiation (10–15 Gy). Materials and Methods Unanesthetized WAG/RijCmcr female rats received single doses of X-irradiation (10, 12 or 15 Gy at 1.615 Gy/minute) to the thorax. Captopril (an angiotensin converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating breathing rate, ex vivo vascular reactivity and histopathology. Survival analysis was undertaken on all animals except those scheduled for sacrifice. Results Survival following a dose of 10 Gy to the thorax was not different from unirradiated rats up to one year. Survival decreased to less than 50%, by 45 weeks after 12 Gy and by 8–9 weeks after 15 Gy. Captopril (17–56 mg/kg/day) improved survival and reduced radiation-induced increases in breathing rate, changes in vascular reactivity and histopathological evidence of injury. Radiation-induced increases in breathing rate were prevented even if captopril was started 1 week following irradiation or if it was discontinued after 5 weeks. Losartan, though effective in reducing mortality was not as efficacious as captopril in mitigating radiation-induced increases in breathing rate or altered vasoreactivity. Conclusions In rats, a moderate thoracic dose of radiation induced pneumonitis and morbidity. These injuries were mitigated by captopril even when it was commenced 1 week after irradiation or if discontinued after 5 weeks following exposure. Losartan was less effective in protecting against radiation-induced changes in vascular reactivity or tachypnea.

Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

“…Based on the propensity score matched analysis and the EORTC and RTOG grading classification our findings suggest that the use of ACEIs during prostate radical radiotherapy is significantly associated with a low grade proctitis. Our findings are in keeping with other studies that have identified the beneficial effects of concurrent use of ACEIs on reducing radiation induced injuries including radiation induced pneumonitis (12), nephritis (29), GI tract toxicity (37) and brain injury (30). A key advantage of our study was that propensity score matched analysis and the EORTC and RTOG grading classification of toxicity was used.…”

Decreasing the Adverse Effects of Cancer Therapy: National Cancer Institute Guidance for the Clinical Development of Radiation Injury Mitigators

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A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

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