Dietary flaxseed prevents radiation-induced oxidative lung damage, inflammation and fibrosis in a mouse model of thoracic radiation injury

January 1, 2009 Human Health and Nutrition Data 0 Comments

Dietary flaxseed prevents radiation-induced oxidative lung damage, inflammation and fibrosis in a mouse model of thoracic radiation injury

Year: 2009
Authors: Lee, J.C. Krochak, R. Blouin, A. Kanterakis, S. Chatterjee, S. Arguiri, E. Vachani, A. et. al.
Publication Name: Cancer Biology & Therapy
Publication Details: Volume 8; Number 1; Pages 1-7.


Flaxseed (FS) has high contents of omega-3 fatty acids and lignans with antioxidant properties. Its use in preventing thoracic X-ray radiation therapy (XRT)-induced pneumonopathy has never been evaluated. We evaluated FS supplementation given to mice given before and post-XRT. FS-derived lignans, known for their direct antioxidant properties, were evaluated in abrogating ROS generation in cultured endothelial cells following gamma radiation exposure. Mice were fed 10% FS or isocaloric control diet for three weeks and given 13.5 Gy thoracic XRT. Lungs were evaluated at 24 hours for markers of radiation-induced injury, three weeks for acute lung damage (lipid peroxidation, lung edema and inflammation), and at four months for late lung damage (inflammation and fibrosis). FS-Lignans blunted ROS generation in vitro, resulting from radiation in a dose-dependent manner. FS-fed mice had reduced expression of lung injury biomarkers (Bax, p21 and TGF-b1) at 24 hours following XRT and reduced oxidative lung damage as measured by malondialdehyde (MDA) levels at 3 weeks following XRT. In addition, FS-fed mice had decreased lung fibrosis as determined by hydroxyproline content and decreased inflammatory cell influx into lungs at 4 months post XRT. Importantly, when Lewis lung carcinoma cells were injected systemically in mice, FS dietary supplementation did not appear to protect lung tumors from responding to thoracic XRT. Dietary FS is protective against pulmonary fibrosis, inflammation and oxidative lung damage in a murine model. Moreover, in this model, tumor protection was not observed. FS lignans exhibited potent radiation-induced ROS scavenging action. Taken together, these data suggest that dietary flaxseed may be clinically useful as an agent to increase the therapeutic index of thoracic XRT by increasing the radiation tolerance of lung tissues. (Authors abstract)

The effectiveness of radiotherapy for thoracic malignancies is limited by the low tolerance of normal lung cells for ionizing radiation. Significant radiation lung injury occurs in 30% of patients irradiated for lung cancer. Highly reactive compounds known as reactive oxygen species (ROS) and reactive nitrogen species (RNS) are induced in large quantities by radiation therapy (XRT). Data suggest that antioxidant molecules and/or enzymes might offer protection of the lung. The use of dietary flaxseed (FS) as a radioprotector against radiation induced lung injury in a murine model of thoracic XRT was assessed in this study. Secoisolariciresinol diglucoside (SDG) from FS has been shown in vitro to have direct hydroxyl radical scavenging properties and to inhibit lipid peroxidation. This study demonstrated that FS can prevent oxidative reactions in lung cells and tissues induced by radiation. Long term post-XRT fibrosis and inflammation were also improved with FS feeding prior to and after XRT. The data suggests that dietary FS may be clinically useful in increasing the therapeutic index of thoracic radiation therapy. Antioxidant cell and tissue protection from radiation using FS and FS-derived SDG was also demonstrated. This study indicated that lignans inhibit radiation-induced ROS generation in endothelial cells (EC). The authors speculated that SDG acted via direct ROS scavenging. The results indicate that creating an antioxidant rich environment at the time of thoracic XRT from FS feeding abrogates the early rise in the proliferative cytokine TGF-β1. A non-significant trend towards decreased tumor size with FS feeding (20% +8% vs. 15% + 8% tumor area for control diet vs. FS supplemented) was noted. FS feeding prior to XRT did not inhibit tumor growth to significantly confound our experimental design. Prolonged FS feeding appears to alter immediate XRT-induced markers of lung damage by providing high levels of circulating antioxidants from the lignans. (Editors comments)

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