Details

Autor(en) / Beteiligte

• Sobue, Sayaka
• Yamai, Kazuaki
• Ito, Mikako
• Ohno, Kinji
• Ito, Masafumi
• Iwamoto, Takashi
• Qiao, Shanlou
• Ohkuwa, Tetsuo
• Ichihara, Masatoshi

Titel

Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents

Ist Teil von

• Molecular and cellular biochemistry, 2015-05, Vol.403 (1-2), p.231-241

Ort / Verlag

Boston: Springer US

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Molecular hydrogen (H 2 ) is an agent with potential applications in oxidative stress-related and/or inflammatory disorders. H 2 is usually administered by inhaling H 2 -containing air (HCA) or by oral intake of H 2 -rich water (HRW). Despite mounting evidence, the molecular mechanism underlying the therapeutic effects and the optimal method of H 2 administration remain unclear. Here, we investigated whether H 2 affects signaling pathways and gene expression in a dosage- or dose regimen-dependent manner. We first examined the H 2 concentrations in blood and organs after its administration and found that oral intake of HRW rapidly but transiently increased H 2 concentrations in the liver and atrial blood, while H 2 concentrations in arterial blood and the kidney were one-tenth of those in the liver and atrial blood. In contrast, inhalation of HCA increased H 2 equally in both atrial and arterial blood. We next examined whether H 2 alters gene expression in normal mouse livers using DNA microarray analysis after administration of HCA and HRW. Ingenuity Pathway Analysis revealed that H 2 suppressed the expression of nuclear factor-kappa B (NF-κB)-regulated genes. Western blot analysis showed that H 2 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 H 2 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 H 2 may act not only through a dose-dependent mechanism but also through a complex molecular network.