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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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The Effects of Long-Term Feeding of Rodent Food Bars on Lipid Peroxidation And Antioxidant Enzyme Levels In Fisher Rats

A specialized rodent food bar diet has been developed and utilized successfully for short-duration shuttle missions. Recent tests conducted in preparation for experiments aboard the International Space Station (ISS) indicated that long-term food bar feeding for three months induced hyperlipidemia in rats. This study examined oxidative stress status in livers of these same animals. Spectrophotometric analysis of 79 Fischer rat livers (40 female and 39 male) for lipid peroxidation (LPO) and superoxide dismutase (SOD) was conducted using Bioxytech LPO-587(TM) assay kit and SOD-525(Tm) assay kit, respectively. The treatment groups consisted of 20 male CHOW and 19 male FOOD BAR rats and 20 female CHOW and 20 female FOOD BAR rats. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures. The male FOOD BAR group LPO mean (3.6 +/- 0.2 mmol/g) was significantly (p less than or equal to 0.05) greater than that of the male CHOW group (2.1 +/-0.1 mmol/g). Moreover the female FOOD BAR group LPO mean (2.9 +/-0.1 mmol/g) was also significantly greater than the female CHOW group mean (2.2 +/-0.1 mmol/g). The mean values for SOD in both male and female groups showed no significant differences between CHOW and FOOD BAR groups. These results show that LPO levels were significantly higher in both the male and female FOOD BAR groups compared to CHOW groups and that there was no concomitant increase in SOD levels across the group. In addition, males showed a greater difference than females in terms of LPO levels. These findings suggest a need for further investigation into the use of the current food bar formulation for long-term experiments such as those planned for the ISS.

Ramirez, Joel↗

Space flight and oxidative stress

Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

long duration↗

Mitochondrial role in cell aging

The experimental studies on the mitochondria of insect and mammalian cells are examined with a view to an analysis of intrinsic mitochondrial senescence, and its relation to the age-related changes in other cell organelles. The fine structural and biochemical data support the concept that the mitochondria of fixed postmitotic cells may be the site of intrinsic aging because of the attack by free radicals and lipid peroxides originating in the organelles as a by-product of oxygen reduction during respiration. Although the cells have numerous mechanisms for counteracting lipid peroxidation injury, there is a slippage in the antioxidant protection. Intrinsic mitochondrial aging could thus be considered as a specific manifestation of oxygen toxicity. It is proposed that free radical injury renders an increasing number of the mitochondria unable to divide, probably because of damage to the lipids of the inner membrane and to mitochondrial DNA.

Miquel, J.↗

Red cell metabolism studies on Skylab

On the basis of these background data, metabolic studies were performed on humans involved in space flight. These studies included the Skylab experiences. The primary purpose of the investigations was to study red cells for: (1) evidences of lipid peroxidation, or (2) changes at various points in the glycolytic pathway. The Skylab missions were an opportunity to study blood samples before, during, and after flight and to compare results with simultaneous controls. No direct evidence that lipid peroxidation had occurred in the red blood cells was apparent in the studies.

Mengel, C. E.↗

Effect of spaceflight on oxidative and antioxidant enzyme activity in rat diaphragm and intercostal muscles

There are limited data regarding changes in oxidative and antioxidant enzymes induced by simulated or actual weightlessness, and any additional information would provide insight into potential mechanisms involving other changes observed in muscles from animals previously flown in space. Thus, the NASA Biospecimen Sharing Program was an opportunity to collect valuable information. Oxidative and antioxidant enzyme levels, as well as lipid peroxidation, were measured in respiratory muscles from rates flown on board Space Shuttle mission STS-54. The results indicated that there was an increasing trend in citrate synthase activity in the flight diaphragm when compared to ground based controls, and there were no significant changes observed in the intercostal muscles for any of the parameters. However, the lipid peroxidation was significantly (p less than 0.05) decreased in the flight diaphragm. These results indicate that 6 day exposure to microgravity may have a different effect on oxidative and antioxidant activity in rat respiratory muscles when compared to data from previous 14 day hindlimb suspension studies.

Lee, Mona D.↗

Red cell metabolism studies on Skylab

Blood samples from Spacelab crewmembers were studied for possible environment effects on red cell components. Analysis involved peroxidation of red cell lipids, enzymes of red cell metabolism, and levels of 2,3-diphosphoglyceric acid and adenosine triphosphate. Results show that there is no evidence of lipid peroxidation, that biochemical effect known to be associated with irreversible red cell damage. Changes observed in glycolytic intermediates and enzymes cannot be directly implicated as indicating evidence of red cell damage.

Mengel, C. E.↗

Vitamin E provides protection for bone in mature hindlimb unloaded male rats

The deleterious effects of skeletal unloading on bone mass and strength may, in part, result from increased production of oxygen-derived free radicals and proinflammatory cytokines. This study was designed to evaluate the ability of vitamin E (alpha-tocopherol), a free-radical scavenger with antiinflammatory properties, to protect against bone loss caused by skeletal unloading in mature male Sprague-Dawley rats. A 2 x 3 factorial design was used with either hindlimb unloading (HU) or normal loading (ambulatory; AMB), and low-dose (LD; 15 IU/kg diet), adequate-dose (AD; 75 IU/kg diet), or high-dose (HD; 500 IU/kg diet) vitamin E (DL-alpha-tocopherol acetate). To optimize the effects of vitamin E on bone, dietary treatments were initiated 9 weeks prior to unloading and continued during the 4-week unloading period, at which time animals were euthanized and blood and tissue samples were collected. Serum vitamin E was dose-dependently increased, confirming the vitamin E status of animals. The HD treatment improved oxidation parameters, as indicated by elevated serum ferric-reducing ability and a trend toward reducing tissue lipid peroxidation. Histomorphometric analysis of the distal femur revealed significant reductions in trabecular thickness (TbTh), double-labeled surface (dLS/BS), and rate of bone formation to bone volume (BFR/BV) due by HU. AMB animals on the HD diet and HU animals on the LD diet had reduced bone surface normalized to tissue volume (BS/TV) and trabecular number (TbN); however, the HD vitamin E protected against these changes in the HU animals. Our findings suggest that vitamin E supplementation provides modest bone protective effects during skeletal unloading.

NASA Discipline Musculoskeletal↗

Acceleration of the aging process by oxygen

Tissue changes induced by hyperoxia have been compared with those of normal aging. Results of investigations using male flies prompt conclusion that normal aging, radiation syndrome, and hyperoxic injury share at least one common feature--lipid peroxidation damage to all mambranes resulting in accumulation of age pigment.

Miquel, J.↗

Oxidative Stress Responses to Simulated Spaceflight in Mineralized and Marrow Compartments of Bone and Associated Vasculature

Long-term spaceflight causes profound changes to the musculoskeletal system attributable to unloading and fluid shifts in microgravity. Future space explorations beyond the earth’s magnetosphere will expose astronauts to space radiation, which may cause additional skeletal deficits that are not yet fully understood. Our long-term goals are twofold: to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures if necessary. Our central hypothesis is that oxidative stress plays a key role in progressive bone loss and vascular dysfunction caused by spaceflight. In animal’s models, overproduction of free radicals is associated with increased bone resorption, lower bone formation, and decrements in bone mineral density and structure which can ultimately lead to skeletal fragility. Evidence in support of a possible causative role for oxidative stress in spaceflight-induced bone loss derive from knockout and transgenic mouse studies and the use of pharmacological interventions with known anti-oxidant properties. In our studies to simulate spaceflight, 16-wk old, male C56Bl/6J mice were assigned to one of four groups: hind limb unloading to simulate weightlessness (HU), normally loaded Controls (‘NL’) (sham irradiated, no hind limb unloading), irradiated at NASA Space Radiation Laboratory ‘IR’ with 1-2Gy of (600MeV/n) alone, or in combination with protons (0.5Gy Protons/0.5Gy 56Fe), (IR) or both hind limb unloaded and irradiated, ‘HU+IR’. Mice were exposed to radiation 3 days after initiating HU and tissues harvested were 1-14 days after initiating treatments for analyses. Results from our laboratories, which employ various biochemical, gene expression, functional, and transgenic animal model methods, implicate dynamic regulation of redox-related pathways by spaceflight-related environmental factors. As one example, we found that combined HU and radiation exposure caused oxidative damage in skeletal tissues (lipid peroxidation) of wildtype mice, whereas bone from transgenic mice that overexpress human catalase in mitochondria were protected. Interestingly, marrow cells grown under culture conditions that select for endothelial progenitor cells (EPC), showed that HU but not IR reduced EPC cell migration; in contrast HU and IR each inhibited growth of marrow-derived osteoblast progenitors. Taken together, these results indicate that unloading and ionizing elicit distinct effects on progenitor and mature cells of vascular and skeletal tissue, and that oxidative damage may contribute to skeletal and vascular deficits that may emerge during extended space travel.

Globus, R. K.↗

Fish oil increases mitochondrial phospholipid unsaturation, upregulating reactive oxygen species and apoptosis in rat colonocytes

We have shown that a combination of fish oil (high in n-3 fatty acids) with the butyrate-producing fiber pectin, upregulates apoptosis in colon cells exposed to the carcinogen azoxymethane, protecting against colon tumor development. We now hypothesize that n-3 fatty acids prime the colonocytes such that butyrate can initiate apoptosis. To test this, 30 Sprague-Dawley rats were provided with diets differing in the fatty acid composition (corn oil, fish oil or a purified fatty acid ethyl ester diet). Intact colon crypts were exposed ex vivo to butyrate, and analyzed for reactive oxygen species (ROS), mitochondrial membrane potential (MMP), translocation of cytochrome C to the cytosol, and caspase-3 activity (early events in apoptosis). The fatty acid composition of the three major mitochondrial phospholipids was also determined, and an unsaturation index calculated. The unsaturation index in cardiolipin was correlated with ROS levels (R = 0.99; P = 0.02). When colon crypts from fish oil and FAEE-fed rats were exposed to butyrate, MMP decreased (P = 0.041); and translocation of cytochrome C to the cytosol (P = 0.037) and caspase-3 activation increased (P = 0.032). The data suggest that fish oil may prime the colonocytes for butyrate-induced apoptosis by enhancing the unsaturation of mitochondrial phospholipids, especially cardiolipin, resulting in an increase in ROS and initiating apoptotic cascade.

Non-NASA Center↗

A system and methodology for measuring volatile organic compounds produced by hydroponic lettuce in a controlled environment

A system and methodology were developed for the nondestructive qualitative and quantitative analysis of volatile emissions from hydroponically grown 'Waldmann's Green' leaf lettuce (Lactuca sativa L.). Photosynthetic photon flux (PPF), photoperiod, and temperature were automatically controlled and monitored in a growth chamber modified for the collection of plant volatiles. The lipoxygenase pathway products (Z)-3-hexenal, (Z)-3-hexenol, and (Z)-3-hexenyl acetate were emitted by lettuce plants after the transition from the light period to the dark period. The volatile collection system developed in this study enabled measurements of volatiles emitted by intact plants, from planting to harvest, under controlled environmental conditions.

NASA Discipline Life Support Systems↗

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Non-NASA Center↗

Lipid Decontamination Procedures for Life Detection Missions

Molecular biosignatures are key targets for current, proposed, and future life detection missions. With the high accuracy and low limit of detection (LOD) that new and future instruments will require, decontamination of life detection hardware is necessary to prevent false positives. Lipids are a molecular biosignature of interest, as they are ubiquitous to all life as we know it, can survive unaltered in the geologic record for longer than any other biomolecule (i.e. billions of years), and form through both biotic and abiotic processes. Lipids display origin-diagnostic molecular patterns that can reveal biotic or abiotic synthesis, so finding them and ascertaining their molecular features is important for potentially detecting evidence of life elsewhere. Traditional methods of decontamination, or contamination control (CC), primarily clean hardware through fabrication in sterile (cleanroom) environments, killing microbes, and removing/flushing contaminants off instrument and spacecraft components. However, research suggests that some standard cleaning methods are either unlikely to remove lipid contaminants or are incompatible with life detection instrument materials. To solve this problem, I propose to find, test, and verify a decontamination method that thoroughly cleans instruments by destroying lipid molecules, but is simultaneously compatible with major materials used in these instruments. I will study the effects of traditional CC methods (including Dry Heat Microbial Reduction and Vapor phase Hydrogen Peroxide) and experimental CC methods (Electron Beam Irradiation) on lipid molecules for application to life detection instrumentation. I will then develop a CC plan for a novel lipid detector (ExCALiBR, Extractor for Chemical Analysis of Lipid Biomarkers in Regolith) searching for lipids in either soil or icy world scenarios. This plan will uphold planetary protection regulation requirements and validate experimental analyses of in-situ life detection tests.

Decontamination↗

Exposure to Carbon Nanotube Material: Assessment of Nanotube Cytotoxicity Using Human Keratinocyte Cells

Carbon nanotubes are new members of carbon allotropes similar to fullerenes and graphite. Because of their unique electrical, mechanical, and thermal properties, carbon nanotubes are important for novel applications in the electronics, aerospace, and computer industries. Exposure to graphite and carbon materials has been associated with increased incidence of skin diseases, such as carbon fiber dermatitis, hyperkeratosis, and naevi. We investigated adverse effects of single-wall carbon nanotubes (SWCNT) using a cell culture of immortalized human epidermal keratinocytes (HaCaT). After 18 h of exposure of HaCaT to SWCNT, oxidative stress and cellular toxicity were indicated by formation of free radicals, accumulation of peroxidative products, antioxidant depletion, and loss of cell viability. Exposure to SWCNT also resulted in ultrastructural and morphological changes in cultured skin cells. These data indicate that dermal exposure to unrefined SWCNT may lead to dermal toxicity due to accelerated oxidative stress in the skin of exposed workers.

Keratinocytes/drug effects↗