Radiation mitigating properties of the lignan component in flaxseed.

Radiation mitigating properties of the lignan component in flaxseed.
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DOI:
10.1186/1471-2407-13-179
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发表时间:
2013-04-04
期刊:
影响因子:
3.8
通讯作者:
Christofidou-Solomidou M
Christofidou-Solomidou M
中科院分区:
医学2区
文献类型:
--
作者:
Pietrofesa R;Turowski J;Tyagi S;Dukes F;Arguiri E;Busch TM;Gallagher-Colombo SM;Solomides CC;Cengel KA;Christofidou-Solomidou M

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全麦亚麻籽 (FS) 及其主要由开环异落叶松树脂醇二葡萄糖苷 (SDG) 组成的木脂素成分 (FLC) 具有有效的肺辐射防护特性,同时不会消除放射治疗的功效。然而,虽然最近在胸部放射性肺炎模型中显示全谷物也具有有效的缓解特性,但谷物中负责减轻肺损伤的生物活性成分从未被发现。肺部可能会因治疗胸部恶性肿瘤而受到放射线照射,或者在放射分散装置爆炸后偶然受到放射线照射。这可能会导致肺部炎症、氧化组织损伤和纤维化。本研究旨在评估 FLC 在放射性肺炎小鼠模型中的辐射缓解作用。我们评估了添加 FLC 的饮食,其含有的 SDG 木脂素水平与 10% 和 20% 全谷物饮食中的水平相当。与等热量对照饮食 (0% FLC) 相比,在单剂量 (13.5 Gy) 胸部 X 射线治疗 (XRT) 后 24、48 或 72 小时,对小鼠 (C57/BL6)(n=15-30 只小鼠/组)给予 10% 或 20% FLC 饮食。 XRT 后 4 个月评估小鼠的血氧、肺部炎症、纤维化、细胞因子和氧化损伤水平以及存活率。 FLC 显着减轻了与辐射相关的动物死亡。具体来说,喂食 0% FLC 的小鼠在 XRT 后 4 个月表现出 36.7% 的存活率,而在 XRT 后 24-72 小时开始喂食 10%-20% FLC 的小鼠的存活率为 60-73.3%。 FLC 还减轻了辐射诱导的肺纤维化,与喂食对照饮食的小鼠相比,XRT 后 24 小时启动 10% FLC 显着降低了纤维化,同时免疫组织化学检测到的相应 TGF-β1 水平也降低了。此外,在辐射暴露后的任何时间点开始 10-20% FLC,减轻了辐射引起的肺损伤,这通过 XRT 后 16 周时支气管肺泡灌洗 (BAL) 蛋白和炎性细胞因子/趋化因子释放的减少来证明。重要的是,木酚素饮食也减轻了气道中的中性粒细胞和整体炎症细胞的浸润,硝基酪氨酸和丙二醛(分别是蛋白质和脂质氧化)的水平。 XRT 后早期给予膳食 FLC 可通过减少炎症、肺损伤和最终纤维化来减轻辐射效应,同时提高生存率。 FLC 可能是一种有用的药物,可以减轻暴露于偶然辐射、吸入放射性同位素或什至在开始放射治疗治疗恶性肿瘤后的个体的辐射副作用。
Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60–73.3% survival in mice fed 10%-20% FLC initiated 24–72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy.
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发表时间: 2010-04-15
影响因子: 7.4
作者:
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发表时间: 2006-04-01
期刊: RISK ANALYSIS
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影响因子: 7
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通讯作者: Vujaskovic, Z