DIETARY FLAXSED AS COUNTERMEASURE TO LUNG DAMAGE RESULTING FROM REPEATED EXPOSURE TO RADIATION AND HYPEROXIA ASSOCIATED WITH SPACE EXPLORATION

All treatment challenges (O2, RAD, O2+RAD) resulted in significant mouse lung injury and inflammation (p<0.05) evidenced by increased bronchoalveolar lavage (BAL) protein levels and significant inflammatory cell infiltration (p<0.003), respectively. Specifically, O2 and O2+RAD-exposed mice had higher oxidative tissue damage (p<0.01), while after just 1 wk of treatment, elevated lung tissue fibrosis was detected (p<0.04). O2 and O2+RAD-exposed mice had higher lung malondialdehyde (MDA) levels (p<0.01), indicative of oxidative tissue damage. After a single cycle of exposure, all groups had elevated blood-derived neutrophil activation markers such as CD18, CD41, and MPO. Having defined the kinetics of tissue damage and determined that 2 weeks is sufficient to induce significant oxidative and inflammatory changes in lung, we proceeded to test FS as a countermeasure to damage. For this, as anticipated, mice fed 0% FS developed significant lung injury and inflammation across all challenges, as evidenced by BAL neutrophils (p<0.003) and increased BAL protein levels, as well as increased oxidative tissue damage (p<0.008), whereas 10% FS ameliorated all adverse parameters. Lung hydroxyproline content also increased in 0% FS-fed mice exposed to RAD and O2+RAD (p<0.001) but abrogated in 10% FS-fed mice. Genes associated with inflammation, such as tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α), and antioxidant enzymes, such as HO-1 and NQO-1, were significantly upregulated in mice fed 0% FS and exposed to O2+RAD. However mice fed 10% FS had inflammatory and antioxidant gene expression levels comparable to baseline values, suggesting the anti-inflammatory and antioxidant potential of dietary FS. CONCLUSION We have characterized a novel murine model of repeated radiation and hyperoxia exposure. We identified EVArelated lung tissue changes associated with inflammation, fibrosis and oxidative tissue damage. We have also identified dietary FS as a potent countermeasure against the lung damaging effects of these oxidative challenges. In conclusion, dietary FS may represent a potential supplement that can be used to abrogate the detrimental health effects of radiation and hyperoxia exposure associated with space exploration.