Space Environment and Redox Homeostasis: A Study on Membrane Lipids and Antioxidant Defenses in Multiple Biological Models

Human exploration and future manned missions beyond Earth to Moon and Mars, imply prolonged exposure to confinement, isolation, altered gravity and cosmic radiation. These stress conditions induce significant physiological and psychophysical changes in astronauts. Understanding human adaptation to space conditions is essential for developing effective countermeasures to safeguard crew health during future long-duration missions. During my doctoral research, space-related stressors, specifically altered gravity, confinement, and isolation affect oxidative stress level and alter plasma membrane lipid composition across various biological models were investigated. This work was conducted within the framework of two space-related projects: “MDS on LDC centrifuge” and “Exposome.” The MDS experiment involved housing mice under hypergravity conditions, while the Exposome project examined the effects of confinement and isolation in submariners during short and long missions, with comparisons to astronauts in actual spaceflight. Oxidative stress was assessed by measuring variations in antioxidant enzyme activity through biochemical assays. To validate these findings, plasma lipid peroxidation markers (e.g. malondialdehyde) and oxidative stress biomarkers isolated in urine samples from astronauts and submariners were quantified by HPLC and ELISA, respectively. Membrane lipid composition was analyzed in erythrocytes of mice and human samples and in cell model using gas chromatography. Additionally, during an international research stay, apoptosis and cell proliferation in MDA MB-231 breast cancer cells exposed to simulated microgravity using a Random Positioning Machine (RPM), alongside assessments of antioxidant and lipid profiles were studied. The results revealed significant alterations in antioxidant molecular systems and membrane lipid composition in all biological models, including cancer cells and erythrocytes isolated from mice, astronauts, submariners. These changes heightened cellular sensitivity to oxidative stress, potentially impairing physiological function. Elevated levels of malondialdehyde, 8-isoprostane, and nucleic acid oxidation markers, particularly after long missions, sustained the increase of oxidative stress. Future analyses of biological samples from extended space missions will deepen our understanding of the combined effects of altered gravity, confinement, and isolation. This knowledge will be pivotal in designing targeted nutritional and pharmacological strategies to mitigate space-induced stress and preserve astronaut health.