Effects of Long-Term Space Flight on Erythrocytes and Oxidative Stress of Rodents

Abstract

Erythrocyte and hemoglobin losses have been frequently observed in humans during space missions; these observations have been designated as “space anemia”. Erythrocytes exposed to microgravity have a modified rheology and undergo hemolysis to a greater extent. Cell membrane composition plays an important role in determining erythrocyte resistance to mechanical stress and it is well known that membrane composition might be influenced by external events, such as hypothermia, hypoxia or gravitational strength variations. Moreover, an altered cell membrane composition, in particular in fatty acids, can cause a greater sensitivity to peroxidative stress, with increase in membrane fragility. Solar radiation or low wavelength electromagnetic radiations (such as gamma rays) from the Earth or the space environment can split water to generate the hydroxyl radical, very reactive at the site of its formation, which can initiate chain reactions leading to lipid peroxidation. These reactive free radicals can react with the non-radical molecules, leading to oxidative damage of lipids, proteins and DNA, etiologically associated with various diseases and morbidities such as cancer, cell degeneration, and inflammation. Indeed, radiation constitutes on of the most important hazard for humans during long-term space flights. With this background, we participated to the MDS tissue-sharing program performing analyses on mice erythrocytes flown on the ISS from August to November 2009. Our results indicate that space flight induced modifications in cell membrane composition and increase of lipid peroxidation products, in mouse erythrocytes. Moreover, antioxidant defenses in the flight erythrocytes were induced, with a significant increase of glutathione content as compared to both vivarium and ground control erythrocytes. Nonetheless, this induction was not sufficient to prevent damages caused by oxidative stress. Future experiments should provide information helpful to reduce the effects of oxidative stress exposure and space anemia, possibly by integrating appropriate dietary elements and natural compounds that could act as antioxidants.

Microgravity Induces Pelvic Bone Loss through Osteoclastic Activity, Osteocytic Osteolysis, and Osteoblastic Cell Cycle Inhibition by CDKN1a/p21

“…One possible mechanism for systemic expression of CDKN1a/p21 in the mouse may be oxidative stress induced by reactive oxygen species (ROS). Elevated levels of ROS can result in increased lipid peroxidation and decreased levels of antioxidants, which have been reported both in spaceflight and hindlimb-unloading studies [55], [56], [57], [58]. Although the effect of CDKN1a/p21 accumulation in muscle and cardiomyocytes is not addressed in this study, it is possible that a systemic activation of CDKN1a/p21 by ROS could be occurring and might interfere with generalized tissue proliferation, repair and regeneration.…”

“…The MAP kinase-ERK pathway is also known to activate the transcription factor Sox9 [71], which is a regulatory factor required for chondrocyte differentiation [72]. Activation of Sox9 by p38-MAP kinase signaling results in chondrocyte growth and differentiation while depression of Sox9 transcription results in cartilage degeneration and osteo-arthritis [55], [73]. Additionally, Sox9 is important for extracellular matrix production [73].…”

Hemolysis during and after 21 days of head-down-tilt bed rest

“…Rizzo et al. () documented heightened antioxidative response of mice erythrocytes to microgravity, of which bed rest is a model.…”

“…Hemoconcentration and erythrocyte losses have also been reported in microgravity (Rizzo et al 2012). Historically space anemia has been explained by a number of possible mechanisms: decreased erythropoietin (EPO) production, erythropoietic suppression, sequestration, blood loss, and enhanced hemolysis (Tavassoli 1982).…”

Spaceflight Influences both Mucosal and Peripheral Cytokine Production in PTN-Tg and Wild Type Mice

“…Details regarding the mouse drawer system and exposure of C57BL/10J Wt and PTN-Tg mice to zero gravity on the ISS have been previously described in “The Mice Drawer System Experiment and the Space Endurance Record-Breaking Mice” (2012) PLoS Collections [8], [11], [49], [50], [51]. Mice were 8 weeks old at launch.…”