As an antioxidant molecule, hydrogen has been received much more attention and reported to be used as the treatment strategy for various diseases. In this study, we hypothesize that systemic delivery of hydrogen saline water may improve the reservation of bone tissue in the tibias and femurs of osteoporotic rats caused by diabetes mellitus (DM), which is characterized by increased levels of oxidative stress and overproducing reactive oxygen species (ROS).
The animals were divided into three groups of 12 animals and lavaged with normal saline (normal control and DM), or hydrogen saline water (DM + HRS). General status, blood glucose level, tibial and femoral mechanical strength, and micro-CT scans of the proximal tibia were recorded and analyzed.
After 12 weeks, the glucose level was significantly decreased in the DM + HRS group compared with that of the DM group. Micro-CT scans showed that bone volume/total volume, connectivity density, trabecular thickness, and trabecular number were significantly increased compared with the DM group. Mechanical results of energy, stiffness and elastic modulus in the DM + HRS group were significantly higher than in the other groups for the tibia and femur.
The results indicate that the systemic delivery of hydrogen saline water, which is safe and well tolerated, preserves bone volume and decreases fracture risks in streptozotocin-induced diabetic status rats, whose bone structure or inherent material properties of bone tissues are changed.
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Jackuliak P, Payer J (2014) Osteoporosis, fractures, and diabetes. Int J Endocrinol 2014:820615. doi:10.1155/2014/820615
Arai M, Shibata Y, Pugdee K, Abiko Y, Ogata Y (2007) Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3-E1 cells. IUBMB Life 59(1):27–33. doi:10.1080/15216540601156188
Xiao L, Miwa N (2017) Hydrogen-rich water achieves cytoprotection from oxidative stress injury in human gingival fibroblasts in culture or 3D-tissue equivalents, and wound-healing promotion, together with ROS-scavenging and relief from glutathione diminishment. Hum Cell 30(2):72–87. doi:10.1007/s13577-016-0150-x
Zhang DQ, Feng H, Chen WC (2013) Effects of hydrogen-rich saline on taurocholate-induced acute pancreatitis in rat. Evid Based Complement Alternat Med 2013:731932
Hayashida K, Sano M, Ohsawa I, Shinmura K, Tamaki K, Kimura K, Endo J, Katayama T, Kawamura A, Kohsaka S, Makino S, Ohta S, Ogawa S, Fukuda K (2008) Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury. Biochem Biophys Res Commun 373(1):30–35. doi:10.1016/j.bbrc.2008.05.165
Chen H, Sun YP, Hu PF, Liu WW, Xiang HG, Li Y, Yan RL, Su N, Ruan CP, Sun XJ, Wang Q (2011) The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats. J Surg Res 167(2):316–322. doi:10.1016/j.jss.2009.07.045
Schoenfeld MP, Ansari RR, Zakrajsek JF, Billiar TR, Toyoda Y, Wink DA, Nakao A (2011) Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight. Med Hypotheses 76(1):117–118. doi:10.1016/j.mehy.2010.08.046
Fu C, Xu D, Wang CY, Jin Y, Liu Q, Meng Q, Liu KX, Sun HJ, Liu MZ (2015) Alpha-lipoic acid promotes osteoblastic formation in H2O2-treated MC3T3-E1 cells and prevents bone loss in ovariectomized rats. J Cell Physiol 230(9):2184–2201. doi:10.1002/jcp.24947
Sun Y, Shuang F, Chen DM, Zhou RB (2013) Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporos Int 24(3):969–978. doi:10.1007/s00198-012-2028-4
Guo JD, Li L, Shi YM, Wang HD, Hou SX (2013) Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol 168(6):1412–1420. doi:10.1111/bph.12036
Feng Y, Wang R, Xu J, Sun J, Xu T, Gu Q, Wu X (2013) Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Curr Eye Res 38(3):396–404. doi:10.3109/02713683.2012.748919
Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL (2017) Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 13(4):208-219. doi:10.1038/nrendo.2016.153
Cunha JS, Ferreira VM, Maquigussa E, Naves MA, Boim MA (2014) Effects of high glucose and high insulin concentrations on osteoblast function in vitro. Cell Tissue Res 358(1):249–256. doi:10.1007/s00441-014-1913-x
Jiao H, Xiao E, Graves DT (2015) Diabetes and its effect on bone and fracture healing. Curr Osteoporos Rep 13(5):327–335. doi:10.1007/s11914-015-0286-8
Sroga GE, Wu PC, Vashishth D (2015) Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone. PLoS One 10(1):e0117046. doi:10.1371/journal.pone.0117046
Garay-Sevilla ME, Nava LE, Malacara JM, Wrobel K, Wrobel K, Perez U (2000) Advanced glycosylation end products (AGEs), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) in patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 16(2):106–113
Al-Hariri M (2016) Sweet bones: the pathogenesis of bone alteration in diabetes. J Diabetes Res 2016:6969040
Nyman JS, Even JL, Jo CH, Herbert EG, Murry MR, Cockrell GE, Wahl EC, Bunn RC, Lumpkin CK Jr, Fowlkes JL, Thrailkill KM (2011) Increasing duration of type 1 diabetes perturbs the strength-structure relationship and increases brittleness of bone. Bone 48(4):733–740. doi:10.1016/j.bone.2010.12.016
Katakura M, Hashimoto M, Tanabe Y, Shido O (2012) Hydrogen-rich water inhibits glucose and alpha,beta -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney. Med Gas Res 2(1):18. doi:10.1186/2045-9912-2-18
Hashimoto M, Katakura M, Nabika T, Tanabe Y, Hossain S, Tsuchikura S, Shido O (2011) Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model. Med Gas Res 1(1):26. doi:10.1186/2045-9912-1-26
Shirahata S, Kabayama S, Nakano M, Miura T, Kusumoto K, Gotoh M, Hayashi H, Otsubo K, Morisawa S, Katakura Y (1997) Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. Biochem Biophys Res Commun 234(1):269–274. doi:10.1006/bbrc.1997.6622
Kim MJ, Kim HK (2006) Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and genetic diabetic mice. L Life Sci 79(24):2288–2292. doi:10.1016/j.lfs.2006.07.027
Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, Kitawaki J, Imai S, Nakano K, Ohta M, Adachi T, Obayashi H, Yoshikawa T (2008) Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 28(3):137–143. doi:10.1016/j.nutres.2008.01.008
Amitani H, Asakawa A, Cheng K, Amitani M, Kaimoto K, Nakano M, Ushikai M, Li Y, Tsai M, Li JB, Terashi M, Chaolu H, Kamimura R, Inui A (2013) Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle. PLoS One 8(1):e53913. doi:10.1371/journal.pone.0053913
Karasu C (2010) Glycoxidative stress and cardiovascular complications in experimentally-induced diabetes: effects of antioxidant treatment. Open Cardiovasc Med J 4:240–256. doi:10.2174/1874192401004010240
Ammar RF Jr, Gutterman DD, Brooks LA, Dellsperger KC (2000) Free radicals mediate endothelial dysfunction of coronary arterioles in diabetes. Cardiovasc Res 47(3):595–601
Baek KH, Oh KW, Lee WY, Lee SS, Kim MK, Kwon HS, Rhee EJ, Han JH, Song KH, Cha BY, Lee KW, Kang MI (2010) Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int 87(3):226–235. doi:10.1007/s00223-010-9393-9
Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31(3):266–300. doi:10.1210/er.2009-0024
Shi Q, Liao KS, Zhao KL, Wang WX, Zuo T, Deng WH, Chen C, Yu J, Guo WY, He XB, Abliz A, Wang P, Zhao L (2015) Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-kappaB pathway. Mediat Inflamm 2015:685043
Ishibashi T, Sato B, Shibata S, Sakai T, Hara Y, Naritomi Y, Koyanagi S, Hara H, Nagao T (2014) Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study. Int Immunopharmacol 21(2):468–473. doi:10.1016/j.intimp.2014.06.001
Suda T, Udagawa N, Nakamura I, Miyaura C, Takahashi N (1995) Modulation of osteoclast differentiation by local factors. Bone 17(2 Suppl):87S–91S
Cai WW, Zhang MH, Yu YS, Cai JH (2013) Treatment with hydrogen molecule alleviates TNFalpha-induced cell injury in osteoblast. Mol Cell Biochem 373(1–2):1–9. doi:10.1007/s11010-012-1450-4
Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314(1):197–207
Li XJ, Zhu Z, Han SL, Zhang ZL (2016) Bergapten exerts inhibitory effects on diabetes-related osteoporosis via the regulation of the PI3K/AKT, JNK/MAPK and NF-kappaB signaling pathways in osteoprotegerin knockout mice. Int J Mol Med 38(6):1661–1672. doi:10.3892/ijmm.2016.2794
Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K (2015) Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Med Gas Res 5:12. doi:10.1186/s13618-015-0035-1
Terawaki H, Hayashi Y, Zhu WJ, Matsuyama Y, Terada T, Kabayama S, Watanabe T, Era S, Sato B, Nakayama M (2013) Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients: a novel approach to suppress oxidative stress in the peritoneal cavity. Med Gas Res 3(1):14. doi:10.1186/2045-9912-3-14
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13(6):688–694. doi:10.1038/nm1577
Conflict of interest
The authors declare that they have no conflict of interest.
This research was supported by the National Nature Science Foundation of China (Award Number 81572162).
The study was approved by the Ethics Board of the Third Hospital of Hebei Medical University and conducted in accordance with the institutional guidelines for the care and treatment of rats.
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Guo, J., Dong, W., Jin, L. et al. Hydrogen-rich saline prevents bone loss in diabetic rats induced by streptozotocin. International Orthopaedics (SICOT) 41, 2119–2128 (2017). https://doi.org/10.1007/s00264-017-3581-4