title: Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration.
abstract: BACKGROUND
  Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures.
  
  
  METHODS
  We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2(O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals.
  
  
  RESULTS
  At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung.
  
  
  CONCLUSIONS
  Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early tissue oxidative damage associated with space exploration.
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Pietrofesa
authors.affiliation: Department of Pathology, Jefferson University Hospital, Philadelphia, PA 19140, USA.
authors.forename: Charalambos C
authors.initials: CC
authors.lastname: Solomides
authors.affiliation: Department of Medicine, Pulmonary Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
keywords: Acute lung injury; Bronchoalveolar lavage; Double-hit; Hyperoxia; Inflammation; Lung fibrosis; Mouse model; Nitrosative stress; Oxidative stress; Radiation pneumonopathy; Space exploration; TGF-β1; Total body irradiation; extravehicular activity