Hydrogen Treatment Protects against Cell Death and Senescence Induced by Oxidative Damage

A Lum  Han; Seong-Hoon  Park; Mi Sung  Park

doi:10.4014/jmb.1608.08011

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Research article

Molecular and Cellular Microbiology (MCM) | Clinical Microbiology and Biomedical Sciences

Hydrogen Treatment Protects against Cell Death and Senescence Induced by Oxidative Damage

A Lum Han ¹, Seong-Hoon Park ^2* and Mi Sung Park ³

¹Department of Family Medicine, Medical Hospital, Wonkwang University, Iksan 54538, Republic of Korea, ²Department of Radiology Medicine, Medical Hospital, Wonkwang University, Iksan 54538, Republic of Korea, ³Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan 54538, Republic of Korea

Received: August 5, 2016; Accepted: October 24, 2016

J. Microbiol. Biotechnol. 2017; 27(2): 365-371

Published February 28, 2017 https://doi.org/10.4014/jmb.1608.08011

Abstract

Hydrogen has potential for preventive and therapeutic applications as an antioxidant. However, micro- and macroparticles of hydrogen in water disappear easily over time. In order to eliminate reactive oxygen species (ROS) related with the aging process, we used functional water containing nanoparticle hydrogen. Nanoparticle hydrogen does not disappear easily and collapse under water after long periods of time. We used murine embryonic fibroblasts that were isolated from 12.5-day embryos of C57BL/6 mice. We investigated the ability of nanoparticle hydrogen in water to suppress hydroxyurea-induced ROS production, cytotoxicity, and the accumulation of β-galactosidase (an indicator of aging), and promote cell proliferation. The accumulation of β-galactosidase in the cytoplasm and the appearance of abnormal nuclei were inhibited by daily treatment of cells with hydrogen water. When the aging process was accelerated by hydroxyurea-induced oxidative stress, the effect of hydrogen water was even more remarkable. Thus, this study showed the antioxidant and antisenescence effects of hydrogen water. Nanoparticle hydrogen water is potentially a potent anti-aging agent.

Keywords

Hydrogen-rich water, hydrogen nanoparticles, anti-aging, antioxidant

References

Halliwell B, Cross CE. 1994. Oxygen-derived species: their relation to human disease and environmental stress. Environ. Health Perspect. 102(Suppl 10): 5-12.
Circu ML, Moyer MP, Harrison L, Aw TY. 2009. Contribution of glutathione status to oxidant-induced mitochondrial DNA damage in colonic epithelial cells. Free Radic. Biol. Med. 47: 1190-1198.
Ricci C, Pastukh V, Leonard J, Turrens J, Wilson G, Schaffer D, Schaffer SW. 2008. Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am. J. Physiol. Cell Physiol. 294: C413-C422.
Harman D. 1956. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11: 298-300.
Beckman KB, Ames BN. 1998. The free radical theory of aging matures. Physiol. Rev. 78: 547-581.
Kregel KC, Zhang HJ. 2007. An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R18-R36.
Loeb LA, Wallace DC, Martin GM. 2005. The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc. Natl. Acad. Sci. USA 102: 18769-18770.
Sanz A, Pamplona R, Barja G. 2006. Is the mitochondrial free radical theory of aging intact? Antioxid. Redox Signal. 8:582-599.
Chen HL, Qu LN, Li QD, Bi L, Huang ZM, Li YH. 2009. Simulated microgravity-induced oxidative stress in different areas of rat brain. Sheng Li Xue Bao [Acta Physiol. Sinica] 61:108-114.
Zhang JY, Liu C, Zhou L, Qu K, Wang R, Tai MH, et al. 2012. A review of hydrogen as a new medical therapy. Hepatogastroenterology 59: 1026-1032.
Buxton GV, Greenstock CL, Helman WP, Ross AB. 1988. Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (•OH/•OH−) in aqueous solution. J. Phys. Chem. Ref. Data 17: 513-886.
Chuai Y, Gao F, Li B, Zhao L, Qian L, Cao F, et al. 2012. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem. J. 442: 49-56.
Gogate PR, Pundit AB. 2005. A review and assessment of hydrodynamic cavitation as a technology for the future. Ultrason. Sonochem. 12: 21-27.
Krishnan JS, Dwivedi P, Moholkar VS. 2006. Numerical investigation into the chemistry induced by hydrodynamic cavitation. Ind. Eng. Chem. Res. 45: 1493-1504.
Takahashi M, Chiba K, Li P. 2007. Free-radical generation from collapsing microbubbles in the absence of a dynamic stimulus. J. Phys. Chem. B 111: 1343-1347.
Oh SH, Yoon SH, Song H, Han JG, Kim J-M. 2013. Effect of hydrogen nanobubble addition on combustion characteristics of gasoline engine. Int. J. Hydrogen Energy 38, 13: 14849-14853.
Agarwal A, Ng WJ, Liu Y. 2011. Principle and applications of microbubble and nanobubble technology for water treatment. Chemosphere 84: 1175-1180.
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. 2010. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome - an open label pilot study. J. Clin. Biochem. Nutr. 46: 140-149.
Kang K-M, Kang Y-N, Choi I-B, Gu Y, Kawamura T, Toyoda Y, Nakao A. 2011. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med. Gas Res. 1: 11.
Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T, et al. 2012. Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology 56: 912-921.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. 2007. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 13: 688-694.
Saitoh Y, Okayasu H, Xiao L, Harata Y, Miwa N. 2008. Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression. Oncol. Res. 17: 247-255.
Xia C, Liu W, Zeng D, Zhu L, Sun X, Sun S. 2013. Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin. Transl. Sci. 6: 372-375.
Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, et al. 2008. Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem. Biophys. Res. Commun. 375: 346-350.
Zhang L, Zhang Y, Zhang X, Li Z, Shen G, Ye M, et al. 2006. Electrochemically controlled formation and growth of hydrogen nanobubbles. Langmuir 22: 8109-8113.
Tanaka K, Matsumoto M. 2008. Nano bubble-size dependence of surface tension and inside pressure. Fluid Dynam. Res. 40:546-553.
Saitoh Y, Okayasu H, Xiao L, Harata Y, Miwa N. 2008. Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression. Oncol. Res. 17: 247-255.
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: 26.

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Article

Research article

J. Microbiol. Biotechnol. 2017; 27(2): 365-371

Published online February 28, 2017 https://doi.org/10.4014/jmb.1608.08011

Hydrogen Treatment Protects against Cell Death and Senescence Induced by Oxidative Damage

A Lum Han ¹, Seong-Hoon Park ^2* and Mi Sung Park ³

¹Department of Family Medicine, Medical Hospital, Wonkwang University, Iksan 54538, Republic of Korea, ²Department of Radiology Medicine, Medical Hospital, Wonkwang University, Iksan 54538, Republic of Korea, ³Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan 54538, Republic of Korea

Received: August 5, 2016; Accepted: October 24, 2016

Abstract

Hydrogen has potential for preventive and therapeutic applications as an antioxidant.
However, micro- and macroparticles of hydrogen in water disappear easily over time. In order
to eliminate reactive oxygen species (ROS) related with the aging process, we used functional
water containing nanoparticle hydrogen. Nanoparticle hydrogen does not disappear easily
and collapse under water after long periods of time. We used murine embryonic fibroblasts
that were isolated from 12.5-day embryos of C57BL/6 mice. We investigated the ability of
nanoparticle hydrogen in water to suppress hydroxyurea-induced ROS production,
cytotoxicity, and the accumulation of β-galactosidase (an indicator of aging), and promote cell
proliferation. The accumulation of β-galactosidase in the cytoplasm and the appearance of
abnormal nuclei were inhibited by daily treatment of cells with hydrogen water. When the
aging process was accelerated by hydroxyurea-induced oxidative stress, the effect of
hydrogen water was even more remarkable. Thus, this study showed the antioxidant and antisenescence effects of hydrogen water. Nanoparticle hydrogen water is potentially a potent
anti-aging agent.

Keywords: Hydrogen-rich water, hydrogen nanoparticles, anti-aging, antioxidant

Abstract

References

Halliwell B, Cross CE. 1994. Oxygen-derived species: their relation to human disease and environmental stress. Environ. Health Perspect. 102(Suppl 10): 5-12.
Circu ML, Moyer MP, Harrison L, Aw TY. 2009. Contribution of glutathione status to oxidant-induced mitochondrial DNA damage in colonic epithelial cells. Free Radic. Biol. Med. 47: 1190-1198.
Ricci C, Pastukh V, Leonard J, Turrens J, Wilson G, Schaffer D, Schaffer SW. 2008. Mitochondrial DNA damage triggers mitochondrial-superoxide generation and apoptosis. Am. J. Physiol. Cell Physiol. 294: C413-C422.
Harman D. 1956. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11: 298-300.
Beckman KB, Ames BN. 1998. The free radical theory of aging matures. Physiol. Rev. 78: 547-581.
Kregel KC, Zhang HJ. 2007. An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R18-R36.
Loeb LA, Wallace DC, Martin GM. 2005. The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc. Natl. Acad. Sci. USA 102: 18769-18770.
Sanz A, Pamplona R, Barja G. 2006. Is the mitochondrial free radical theory of aging intact? Antioxid. Redox Signal. 8:582-599.
Chen HL, Qu LN, Li QD, Bi L, Huang ZM, Li YH. 2009. Simulated microgravity-induced oxidative stress in different areas of rat brain. Sheng Li Xue Bao [Acta Physiol. Sinica] 61:108-114.
Zhang JY, Liu C, Zhou L, Qu K, Wang R, Tai MH, et al. 2012. A review of hydrogen as a new medical therapy. Hepatogastroenterology 59: 1026-1032.
Buxton GV, Greenstock CL, Helman WP, Ross AB. 1988. Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals (•OH/•OH−) in aqueous solution. J. Phys. Chem. Ref. Data 17: 513-886.
Chuai Y, Gao F, Li B, Zhao L, Qian L, Cao F, et al. 2012. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem. J. 442: 49-56.
Gogate PR, Pundit AB. 2005. A review and assessment of hydrodynamic cavitation as a technology for the future. Ultrason. Sonochem. 12: 21-27.
Krishnan JS, Dwivedi P, Moholkar VS. 2006. Numerical investigation into the chemistry induced by hydrodynamic cavitation. Ind. Eng. Chem. Res. 45: 1493-1504.
Takahashi M, Chiba K, Li P. 2007. Free-radical generation from collapsing microbubbles in the absence of a dynamic stimulus. J. Phys. Chem. B 111: 1343-1347.
Oh SH, Yoon SH, Song H, Han JG, Kim J-M. 2013. Effect of hydrogen nanobubble addition on combustion characteristics of gasoline engine. Int. J. Hydrogen Energy 38, 13: 14849-14853.
Agarwal A, Ng WJ, Liu Y. 2011. Principle and applications of microbubble and nanobubble technology for water treatment. Chemosphere 84: 1175-1180.
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. 2010. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome - an open label pilot study. J. Clin. Biochem. Nutr. 46: 140-149.
Kang K-M, Kang Y-N, Choi I-B, Gu Y, Kawamura T, Toyoda Y, Nakao A. 2011. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med. Gas Res. 1: 11.
Kawai D, Takaki A, Nakatsuka A, Wada J, Tamaki N, Yasunaka T, et al. 2012. Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology 56: 912-921.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. 2007. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 13: 688-694.
Saitoh Y, Okayasu H, Xiao L, Harata Y, Miwa N. 2008. Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression. Oncol. Res. 17: 247-255.
Xia C, Liu W, Zeng D, Zhu L, Sun X, Sun S. 2013. Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin. Transl. Sci. 6: 372-375.
Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, et al. 2008. Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem. Biophys. Res. Commun. 375: 346-350.
Zhang L, Zhang Y, Zhang X, Li Z, Shen G, Ye M, et al. 2006. Electrochemically controlled formation and growth of hydrogen nanobubbles. Langmuir 22: 8109-8113.
Tanaka K, Matsumoto M. 2008. Nano bubble-size dependence of surface tension and inside pressure. Fluid Dynam. Res. 40:546-553.
Saitoh Y, Okayasu H, Xiao L, Harata Y, Miwa N. 2008. Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression. Oncol. Res. 17: 247-255.
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: 26.