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Targeting the Renin-angiotensin system combined with an antioxidant is highly effective in mitigating radiation-induced lung damage.

International journal of radiation oncology, biology, physics (2014-05-29)
Javed Mahmood, Salomeh Jelveh, Asif Zaidi, Susan R Doctrow, Meetha Medhora, Richard P Hill
ABSTRACT

To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Captopril, meets USP testing specifications
Sigma-Aldrich
Captopril, ≥98% (HPLC), powder
USP
Captopril, United States Pharmacopeia (USP) Reference Standard
Captopril, European Pharmacopoeia (EP) Reference Standard
Supelco
Captopril, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
8-Hydroxy-2′-deoxyguanosine, ≥98% (TLC)
Captopril for system suitability, European Pharmacopoeia (EP) Reference Standard