Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice.

Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed?s therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. We evaluated the effects of a 10% FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n=15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 +/- 7.1 to 110.2 +/- 7.7 μg/ml (Mean +/- SEM) in all irradiated FS-fed mouse groups, as compared to 138 +/- 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0% FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of specific inflammatory cytokines in FS-fed mice. Dietary FS given post-XRT mitigates radiation effects by decreasing pulmonary fibrosis, inflammation, cytokine secretion and lung damage while enhancing mouse survival. Dietary supplementation of FS may be a useful adjuvant treatment mitigating adverse effects of radiation in individuals exposed to inhaled radioisotopes or incidental radiation. (Author's abstract)
This is the first publication to demonstrate the role of FS in boosting survival and mitigating the acute and chronic damage induced by X-ray radiation exposure of lung tissues. FS improved survival and body weight of mice fed with FS when diet was given prior to XRT and also when diet was started 2, 4 and 6 weeks after XRT. The FS diet mitigated the deleterious effects of XRT by: a) improving pulmonary hemodynamics and blood oxygenation levels, b) decreasing lung injury by lowering BAL protein levels, c) reducing pulmonary fibrosis by decreasing collagen content of lung tissues, d) reducing lung inflammation by decreasing WBC influx into the airways and by e) oxidative modification of mouse lungs as evidenced by levels of lipid peroxidation. BAL cytokine analysis supports a reduction in the chronic inflammatory profile of irradiated lungs as a result of the FS diet. FS diet led to a significant drop in the lipid peroxidation (LP) levels in all the FS-fed experimental mouse groups.  BAL protein level is the most direct and reliable measure of lung injury. In addition, several cytokines associated with inflammation were significantly lower in irradiated FS-fed mice as compared to irradiated mice on control diet. Dietary supplementation of FS decreased IL-6 levels, indicating a low inflammatory state. The authors state that dietary FS is a potential agent in mitigating radiation damage and as such, the investigators are currently exploring dietary formulations of FS components, to identify the chief bioactive ingredient(s) that mitigate radiation effects. (Editor's Comments)