caa a22 4500 606236678 CHVBK 20210128101249.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s11010-015-2353-y doi (NATIONALLICENCE)springer-10.1007/s11010-015-2353-y Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents [Elektronische Daten] [Sayaka Sobue, Kazuaki Yamai, Mikako Ito, Kinji Ohno, Masafumi Ito, Takashi Iwamoto, Shanlou Qiao, Tetsuo Ohkuwa, Masatoshi Ichihara] Molecular hydrogen (H2) is an agent with potential applications in oxidative stress-related and/or inflammatory disorders. H2 is usually administered by inhaling H2-containing air (HCA) or by oral intake of H2-rich water (HRW). Despite mounting evidence, the molecular mechanism underlying the therapeutic effects and the optimal method of H2 administration remain unclear. Here, we investigated whether H2 affects signaling pathways and gene expression in a dosage- or dose regimen-dependent manner. We first examined the H2 concentrations in blood and organs after its administration and found that oral intake of HRW rapidly but transiently increased H2 concentrations in the liver and atrial blood, while H2 concentrations in arterial blood and the kidney were one-tenth of those in the liver and atrial blood. In contrast, inhalation of HCA increased H2 equally in both atrial and arterial blood. We next examined whether H2 alters gene expression in normal mouse livers using DNA microarray analysis after administration of HCA and HRW. Ingenuity Pathway Analysis revealed that H2 suppressed the expression of nuclear factor-kappa B (NF-κB)-regulated genes. Western blot analysis showed that H2 attenuated ERK, p38 MAPK, and NF-κB signaling in mouse livers. Finally, we evaluated whether the changes in gene expression were influenced by the route of H2 administration and found that the combination of both HRW and HCA had the most potent effects on signaling pathways and gene expression in systemic organs, suggesting that H2 may act not only through a dose-dependent mechanism but also through a complex molecular network. Springer Science+Business Media New York, 2015 Molecular hydrogen nationallicence Gene expression nationallicence NF-κB nationallicence p38 nationallicence ERK nationallicence Sobue Sayaka Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut Yamai Kazuaki Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut Ito Mikako Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan aut Ohno Kinji Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan aut Ito Masafumi Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 173-0015, Tokyo, Japan aut Iwamoto Takashi Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut Qiao Shanlou Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut Ohkuwa Tetsuo Department of Materials Science and Engineering, Nagoya Institute of Technology, Graduate School of Engineering, 466-8555, Nagoya, Japan aut Ichihara Masatoshi Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 231-241 0300-8177 403:1-2<231 2015 403 11010 https://doi.org/10.1007/s11010-015-2353-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2353-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sobue Sayaka Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut NATIONALLICENCE 700 1- Yamai Kazuaki Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut NATIONALLICENCE 700 1- Ito Mikako Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan aut NATIONALLICENCE 700 1- Ohno Kinji Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 466-8550, Nagoya, Japan aut NATIONALLICENCE 700 1- Ito Masafumi Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 173-0015, Tokyo, Japan aut NATIONALLICENCE 700 1- Iwamoto Takashi Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut NATIONALLICENCE 700 1- Qiao Shanlou Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut NATIONALLICENCE 700 1- Ohkuwa Tetsuo Department of Materials Science and Engineering, Nagoya Institute of Technology, Graduate School of Engineering, 466-8555, Nagoya, Japan aut NATIONALLICENCE 700 1- Ichihara Masatoshi Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 487-8501, Kasugai, Japan aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 231-241 0300-8177 403:1-2<231 2015 403 11010