Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight

Schoenfeld, Michael P.; Ansari, Rafat R.; Zakrajsek, James J.; Billiar, Timothy R.; Toyoda, Yoshiya; Wink, David A.; Nakao, Atsunori

doi:10.1016/j.mehy.2010.08.046

Cited by 31 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

Section: Discussionmentioning

confidence: 77%

“…P38-MAP kinase down-regulation and loss of Sox9 transcriptional activation may therefore have important implications for cartilage health and regeneration, and matrix production in spaceflight. Rps6kb1, a down-stream effector of the Pi3K/Akt/mTOR pathway, was also down-regulated in spaceflight (Table 3), and is involved in cell proliferation through the activation of protein synthesis by Eif4e and inhibition of apoptosis through phosphorylation of BAD (for full review see [56]). …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2013

View full text Add to dashboard Cite

Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arrest during osteogenesis may also contribute to bone loss in space. To test this possibility, we exposed 16-week-old female C57BL/6J mice (n = 8) to microgravity for 15-days on the STS-131 space shuttle mission. Analysis of the pelvis by µCT shows decreases in bone volume fraction (BV/TV) of 6.29%, and bone thickness of 11.91%. TRAP-positive osteoclast-covered trabecular bone surfaces also increased in microgravity by 170% (p = 0.004), indicating osteoclastic bone degeneration. High-resolution X-ray nanoCT studies revealed signs of lacunar osteolysis, including increases in cross-sectional area (+17%, p = 0.022), perimeter (+14%, p = 0.008), and canalicular diameter (+6%, p = 0.037). Expression of matrix metalloproteinases (MMP) 1, 3, and 10 in bone, as measured by RT-qPCR, was also up-regulated in microgravity (+12.94, +2.98 and +16.85 fold respectively, p<0.01), with MMP10 localized to osteocytes, and consistent with induction of osteocytic osteolysis. Furthermore, expression of CDKN1a/p21 in bone increased 3.31 fold (p<0.01), and was localized to osteoblasts, possibly inhibiting the cell cycle during tissue regeneration as well as conferring apoptosis resistance to these cells. Finally the apoptosis inducer Trp53 was down-regulated by −1.54 fold (p<0.01), possibly associated with the quiescent survival-promoting function of CDKN1a/p21. In conclusion, our findings identify the pelvic and femoral region of the mouse skeleton as an active site of rapid bone loss in microgravity, and indicate that this loss is not limited to osteoclastic degradation. Therefore, this study offers new evidence for microgravity-induced osteocytic osteolysis, and CDKN1a/p21-mediated osteogenic cell cycle arrest.

show abstract

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Some investigators even proposed application hydrogen therapy in space flight 77. Definition of hydrogen as a kind of antioxidant seems cannot explain all radioprotective effects of hydrogen.…”

Section: Future Directionsmentioning

confidence: 99%

Hydrogen as a New Class of Radioprotective Agent

Qian¹,

Shen²,

Chuai³

et al. 2013

Int. J. Biol. Sci.

View full text Add to dashboard Cite

It is well known that most of the ionizing radiation-induced damage is caused by hydroxyl radicals (·OH) follows radiolysis of H2O. Molecular hydrogen (H2) has antioxidant activities by selectively reducing ·OH and peroxynitrite(ONOO-). We firstly hypothesized and demonstrated the radioprotective effect of H2 in vitro and in vivo, which was also repeated on different experimental animal models by different departments. A randomized, placebo-controlled study showed that consumption of hydrogen-rich water reduces the biological reaction to radiation-induced oxidative stress without compromising anti-tumor effects. These encouraging results suggested that H2 represents a potentially novel preventative strategy for radiation-induced oxidative injuries. H2 is explosive. Therefore, administration of hydrogen-rich solution (physiological saline/pure water/other solutions saturated with H2) may be more practical in daily life and more suitable for daily consumption. This review focuses on major scientific and clinical advances of hydrogen-rich solution/H2 as a new class of radioprotective agent.

show abstract

“…H 2 application for hemodialysis treatment H 2 -enriched water rendered by water electrolysis and biological effects With the recent progress of H 2 science, therapeutic application of H 2 has become a clinical challenge [73,74]. However, practical aspects of how to deliver H 2 in a safe and stable manner at the bedside have been a concern.…”

Section: The Hydrogen Gas Molecule As a Biological Antioxidantmentioning

confidence: 99%

The hydrogen molecule as antioxidant therapy: clinical application in hemodialysis and perspectives

2016

View full text Add to dashboard Cite

Increased oxidative stress and pro-inflammatory conditions, commonly present in chronic dialysis patients, are thought to be enhanced during hemodialysis (HD) and to be associated with the excess morbidity and mortality seen in these patients. The hydrogen molecule (H 2 ) has a unique biological capacity to act as an antioxidative and anti-inflammatory substance. In light of accumulating evidence from animal studies showing protective effects against organ damage during ischemia and inflammation, development of H 2 treatments for HD patients has become a challenging clinical goal. An HD system utilizing a water electrolysis technique that renders large amounts of H 2 -enriched water has been developed. During HD with an H 2 -enriched solution (approximately 50 ppb H 2 ), markers of increased oxidative stress (such as interleukin-6, myeloperoxidase, methemoglobin, increased lymphocyte apoptosis, and high blood pressure) are suppressed. These findings indicate that the use of an H 2 -enriched solution may prove to be a novel approach to ameliorate dialysis-related complications. This manuscript reviews the recent progress in H 2 research and the use of H 2 in HD patients, including a description of a water electrolysis technique that delivers large amounts of H 2 -enriched water for use in clinical settings.

show abstract

Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight

Cited by 31 publications

References 14 publications

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

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

Hydrogen as a New Class of Radioprotective Agent

The hydrogen molecule as antioxidant therapy: clinical application in hemodialysis and perspectives

Contact Info

Product

Resources

About