Targeting the Renin-angiotensin system combined with an antioxidant is highly effective in mitigating radiation-induced lung damage.
Targeting the Renin-angiotensin system combined with an antioxidant is highly effective in mitigating radiation-induced lung damage.
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DOI：
10.1016/j.ijrobp.2014.03.048
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发表时间：
2014-07-15
影响因子：
7
通讯作者：
Hill, Richard P.
中科院分区：
文献类型：
--
作者：
Mahmood, Javed;Jelveh, Salomeh;Zaidi, Asif;Doctrow, Susan R.;Medhora, Meetha;Hill, Richard P.
我们研究了卡托普利联合抗氧化剂(EUKarion-207)抑制肾素血管紧张素系统(RAS)以减轻放射性肺损伤的结果。对雌性SD大鼠胸腔进行单次照射，剂量为11Gy.照射后1周开始给予卡托普利40 mg/kg/d，皮下注射EUK-207(8 mg/kg/d)，持续至照射后14周。监测大鼠的呼吸频率，直到32wks PI处死大鼠，以肺组织羟脯氨酸含量评估肺纤维化。免疫组织化学方法检测肺组织细胞因子转化生长因子-β-1和巨噬细胞活化情况。用8-羟基-2-脱氧鸟苷(8-OHdG)检测DNA氧化损伤，用T-bar法检测脂质过氧化反应。经药物治疗后，受照大鼠呼吸频率的增加明显减少。治疗后32周，8-羟色胺和丙二醛含量、活化巨噬细胞和细胞因子转化生长因子-β-1水平显著降低。通过联合使用卡托普利和EUK-207，可以观察到这些辐射效应几乎完全缓解。卡托普利和EUK-207在给药1-14周后，至少可减轻放射性肺损伤32周。总体而言，卡托普利和EUK-207联合使用比单独使用药物更有效。
We investigated the outcome of suppression of renin angiotensin system (RAS) using Captopril combined with an antioxidant (EUKarion-207) for mitigation of radiation-induced lung damage in rats. The thoracic cavity of female Sprague-Dawley (SD) rats was irradiated with single dose of 11 Gy. Treatment with Captopril at a dose of 40 mg/kg/day in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week (wk) post-irradiation (PI) and continuing until 14 wks PI. Breathing rate was monitored until the rats were sacrificed at 32 wks PI when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine, Transforming Growth Factor (TGF)-β1, and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG) 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-OHdG and malondialdehyde levels, and levels of activated macrophages and the cytokine TGF-β1 at 32 wks. 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 wks PI following treatment given 1–14 wks PI. Overall the combination of Captopril and EUK-207 was more effective than the individual drugs used alone.
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DOI：
10.1111/j.1440-1843.2012.02247.x
发表时间：
2012-11
期刊：
Respirology (Carlton, Vic.)
影响因子：
--
作者：
Molthen RC;Wu Q;Fish BL;Moulder JE;Jacobs ER;Medhora MM
通讯作者：
Medhora MM
影响因子：
5.7
作者：
Langan, Aimee R.;Khan, Mohammed A.;Hill, Richard P.
通讯作者：
Hill, Richard P.
DOI：
10.1016/j.ijrobp.2011.05.081
发表时间：
2012-05-01
影响因子：
7
作者：
Cohen, Eric P.;Bedi, Manpreet;Irving, Amy A.;Jacobs, Elizabeth;Tomic, Rade;Klein, John;Lawton, Colleen A.;Moulder, John E.
通讯作者：
Moulder, John E.
DOI：
10.1016/s0360-3016(00)00482-x
发表时间：
2000-07-01
影响因子：
7
作者：
Rübe, CE;Uthe, D;Rübe, C
通讯作者：
Rübe, C
影响因子：
2.6
作者：
Mahmood J;Jelveh S;Calveley V;Zaidi A;Doctrow SR;Hill RP
通讯作者：
Hill RP