Space flight missions may require crewmembers to conduct extravehicular activities (EVA) for repair, maintenance, or scientific purposes. EVAs should total no more than 24 hours weekly per crew member. During each EVA, crewmembers are subjected to a number of challenges that may induce oxidative tissue damage and thus present a threat to their health and therefore pose a limitation to the success of the mission. One such challenge is the exposure to 100% oxygen as well as to low levels of total body cosmic/galactic radiation that crewmembers will be exposed to during an EVA. Currently, no studies have addressed this “double hit” hyperoxia/radiation effect so the investigators developed and characterized a novel, mouse model of repeated total body radiation and hyperoxia exposure. Preliminary studies identified acute lung damage associated with such treatment so the goal of the proposed study is to further characterize the acute damage and most importantly, to provide information on the long-term effects of such an exposure (Aim 1). Additionally, initial findings suggested that dietary administration of whole grain dietary flaxseed (FS) ameliorated adverse acute effects in the same model. The investigating team was the first to show in murine models of radiation and hyperoxic lung injury the protective properties of FS. Importantly, lignan phenolics in FS such as secoisolariciresinol diglucoside (SDG), are known antioxidant, anti-inflammatory and anticarcinogenic agents. Investigators hypothesize that FS and FS lignans will be effective countermeasures of this double-hit toxicity to lung tissues (Aim 2). They plan to further explore the usefulness of FS and SDG in both acute and chronic oxidative lung damage in this model. FS and specifically SDG are safe, readily available and thus, attractive candidates to evaluate as oxidative damage countermeasures in the proposed double hit radiation/hyperoxia model. Data from this work are relevant to EVA-related pathophysiology associated with space exploration.
1. Characterize oxidative lung damage from repeated Radiation/hyperoxia exposure in a novel mouse model of space-flight related challenge.
2. Evaluate usefulness of dietary FS and FLC as countermeasure to oxidative lung injury in a mouse model of radiation/hyperoxia relevant to space flight challenges.
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Mouse cohorts were placed on a flaxseed (FS) or flaxseed lignan component (FLC) diets. Lung tissues, as well as brain, and blood will be collected after one month (acute) and compared to that collected after two, three, four months (Chronic) with respect to oxidative damage, inflammation, and fibrosis.
Since the beginning of the study, the investigators have completed Specific Aim 1 and have initiated Aim 2 (currently on-going). Their results were presented at NASA’s annual Human Research Program workshop at Galveston, Texas in early 2013.
Specific Aim 1: Characterize oxidative lung damage from repeated Radiation/hyperoxia exposure in a novel mouse model of space-flight related challenge.
The investigators have characterized significant, chronic lung changes in their murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation) and increased pulmonary fibrosis. These findings, along with the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead investigators to conclude that in their model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration.
Specific Aim 2: Evaluate usefulness of dietary FS and FLC as countermeasure to oxidative lung injury in a mouse model of radiation/hyperoxia relevant to space flight challenges.
This part of the study is currently in progress.