Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice.
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ABSTRACT:
SUBMITTER: Iketani M
PROVIDER: S-EPMC6235982 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Molecular hydrogen is a hopeful agent for oxidative stress-related and/or inflammatory disorders. However, the molecular mechanism for these therapeutic effects of hydrogen still remains to be fully elucidated. We examined whether molecular hydrogen alters gene expression levels in normal mouse livers by DNA microarray analysis. We identified 140 mouse genes that were upregulated (31 genes) or downregulated (109 genes) after three weeks of the inhalation of 2% hydrogen-containing air with oral intake of hydrogen-rich water. Ingenuity Pathway Analysis revealed that hydrogen influenced expression of NF-kB- and NFAT-regulated genes. Western blot analysis showed that hydrogen attenuated Erk, p38 MAPK, and NF-kB signaling in mouse livers.
2014-08-01 | GSE48826 | GEO
Project description:Molecular hydrogen is a hopeful agent for oxidative stress-related and/or inflammatory disorders. However, the molecular mechanism for these therapeutic effects of hydrogen still remains to be fully elucidated. We examined whether molecular hydrogen alters gene expression levels in normal mouse livers by DNA microarray analysis. We identified 140 mouse genes that were upregulated (31 genes) or downregulated (109 genes) after three weeks of the inhalation of 2% hydrogen-containing air with oral intake of hydrogen-rich water. Ingenuity Pathway Analysis revealed that hydrogen influenced expression of NF-kB- and NFAT-regulated genes. Western blot analysis showed that hydrogen attenuated Erk, p38 MAPK, and NF-kB signaling in mouse livers. We divided 10-week male BALB/c mice into two groups: 1) control group: fed with control water in air (n=4), 2) hydrogen-treated group: fed with hydrogen-rich water in 2% hydrogen/98% air (n=4). Hydrogen-rich water (0.7mM dissolved hydrogen) was generated from distilled water with 0.44 mM Na2SO4 using Aquela Blue, a water-electrolyzing device to produce electrolyzed hydrogen-saturated water near neutral pH (MiZ Co., Ltd, Fujisawa, Japan). The control water was prepared by gently stirring hydrogen-rich water in open air for 24 hours. Hydrogen-rich water or control water was administrated ad libitum to the mice with a 50-ml closed glass vessel equipped with an outlet line having a ball bearing. After 3-week rearing, the mice were sacrificed and their livers were removed for RNA extraction. We mixed equal amount of RNA from four mice in each group (control vs. hydrogen-treated) and compared gene expression profile by microarray.
2014-08-01 | E-GEOD-48826 | biostudies-arrayexpress
Project description:Oxidative damage is involved in age-related inflammatory reactions. The anti-oxidative effects of hydrogen-rich water suppress oxidative damage, which may aid in inhibiting age-related inflammatory reactions. We investigated the effects of drinking hydrogen-rich water on aging periodontal tissues in healthy rats. Four-month-old male Fischer 344 rats (n = 12) were divided into two groups: the experimental group (hydrogen-rich water treatment) and the control group (distilled water treatment). The rats consumed hydrogen-rich water or distilled water until 16 months of age. The experimental group exhibited lower periodontal oxidative damage at 16 months of age than the control group. Although protein expression of interleukin-1β did not differ, gene expression of Nod-like receptor protein 3 inflammasomes was activated in periodontal tissues from the experimental group as compared with the control group. Drinking hydrogen-rich water is proposed to have anti-aging effects on periodontal oxidative damage, but not on inflammatory reactions in healthy rats.
| S-EPMC4078318 | biostudies-literature
Project description:Chronic stressors, such as chronic isolation in social mammals, can elevate glucocorticoids, which can affect cellular mechanisms of aging, including increased levels of oxidative stress and shortened telomere lengths. Recent work in the selectively social prairie vole (Microtus ochrogaster) suggests that oxytocin and social support may mitigate some of the negative consequences of social isolation, possibly by reducing glucocorticoid levels. We investigated the influences of isolation, social support, and daily oxytocin injections in female prairie voles. Glucocorticoid levels, oxidative damage, telomere length, and anhedonia, a behavioral index of depression, were measured throughout the study. We found that six weeks of chronic isolation led to increased glucocorticoid levels, oxidative damage, telomere degradation and anhedonia. However, daily oxytocin injections in isolated voles prevented these negative consequences. These findings demonstrate that chronic social isolation in female prairie voles is a potent stressor that results in depression-like behavior and accelerated cellular aging. Importantly, oxytocin can completely prevent the negative consequences of social isolation.
| S-EPMC7476076 | biostudies-literature
Project description:Background and purposeAccumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. Recently, it was demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant activity. The aim of the present work was to investigate the effect of hydrogen water (HW) consumption on ovariectomy-induced osteoporosis.Experimental approachOvariectomized rats were fed with HW (1.3 ± 0.2 mg·L⁻¹) for 3 months. Then, blood was collected and femur and vertebrae were removed for evaluation of the effect of HW on bone.Key resultsHW consumption in ovariectomized rats had no significant effect on oestrogen production, but prevented the reduction of bone mass including bone mineral content and bone mineral density in femur and vertebrae, and preserved mechanical strength including ultimate load, stiffness, and energy, and bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in femur, and preserved mechanical strength including ultimate load and stiffness, and bone structure including trabecular bone volume fraction and trabecular number in vertebrae. In addition, treatment with HW abated oxidative stress and suppressed IL-6 and TNF-α mRNA expressions in femur of ovariectomized rats; treatment with HW increased femur endothelial NOS activity and enhanced circulating NO level in ovariectomized rats.Conclusions and implicationsHW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.
| S-EPMC3596646 | biostudies-literature
Project description:Dehydration is one of the intrauterine abnormalities that could lead to fetal growth retardation and to increase the risk of a variety of adult diseases later in life. This study were to determine the impact of hydrogen-rich water (HRW) supplementation on placental angiotensin II type 1 receptor and placental oxidative stress induced by water restriction. Pregnant Wistar rat were randomly assigned to one of the three groups (n =12 per group). In control group, pure water and food were supplied ad libitum. Water restriction group and HRW group were respectively given pure water and HRW with free access to food, excepting only one hour was available for drinking from day 7 to day 17 of pregnancy. The placental damages and biomarkers of stress were detected by histopathology, immunohistochemistry and western blot, as well as serological test were performed. We demonstrated that maternal water restriction resulted in reduced urine volume and increased serum osmotic pressure, along with decreased fetus weight and crown-rump length. Although placental weight and the number of fetuses had no significant difference among groups, the placental efficiency significantly increased after the oral administration of HRW to the mothers. Meanwhile, the serological derivatives of reactive oxygen metabolites decreased, a significant improvement of placental microstructure with more developed junctional zone and denser labyrinth was manifested, the upregulated expression of angiotensin II type 1 receptor, nuclear facto?B, malondialdehyde, 8-hydroxydeoxyguanosine, p38, c-Jun N-terminal kinase and down-regulation of superoxide dismutase were revealed in the placenta. Collectively, HRW administration is able to effectively attenuate placental stress induced by water restriction.
| S-EPMC6178645 | biostudies-other
Project description:AIM:To investigate the efficacy and safety of mineral water with a high content of hydrogen carbonate in patients with heartburn. METHODS:This open, single-center, single-arm clinical pilot study enrolled 50 patients, 18-64 years old, who had been suffering from heartburn at least twice a week for at least 3 mo before entering the study. Pharmacological treatment of heartburn was not permitted, and patients with severe organic diseases were excluded. After a run-in period of one week, the participants received 1.5 L of the test water for the following 6 wk; 300 mL with meals t.i.d., the remainder to be drunk throughout the day. During the trial, there were five visits at the study center (screening, baseline, two interim visits and the final visit). The efficacy endpoints included incidence and duration of heartburn episodes per week by patient's self-assessment (heartburn diary) as well as changes in symptom severity as per symptom specific questionnaires [Reflux Disease Questionnaire (RDQ); Quality of Life in Reflux and Dyspepsia (QOLRAD); Gastrointestinal Quality of Life Index] and overall health-related quality of life per SF-12 (12-question short form) at each visit. At the end of the study, patients and investigators independently rated the overall efficacy of the test water on a 4-point Likert scale. Safety was assessed by evaluation of adverse events (AEs), vital signs (heart rate, blood pressure) and laboratory parameters. Changes from initial to final examinations were assessed by the non-parametric Wilcoxon test; categorical variables were compared using the ?(2) test, and for more than 5 categories, by the U-test. RESULTS:Twenty-eight participants were men, 22 women. The mean age of the patients in the full analysis set/intention-to treat population (FAS/ITT) was 40.6 years. Forty-two participants completed the study according to the study protocol and formed the per-protocol set (PP population); 48 participants drank the water at least once as requested and were analyzed as ITT population. The occurrence of heartburn was statistically significantly reduced at wk 6 in both the ITT and the PP populations. At wk 6, the mean number of heartburn episodes/week decreased by 5.1 episodes (P < 0.001) and the mean duration of heartburn symptoms by 19 min (ITT) (P = 0.002). The frequency of heartburn symptoms was reduced in 89.6% of the patients (P < 0.001), and the duration of symptoms in 79.2% of patients (ITT) (P < 0.001). All dimensions of the RDQ (heartburn, regurgitation, gastro-esophageal reflux disease symptoms, dyspepsia) showed a significant improvement at 6 wk. Likewise, disease-specific quality of life improved significantly (QOLRAD, GIQLI). Overall, 89.4% of patients rated the efficacy of the test water as "good" or "very good", as did the investigators for 91.5% of the patients. There were no serious AEs. After 6 wk, systolic and diastolic blood pressure values decreased slightly but significantly [-3.5 and -3.0 mmHg, respectively (P = 0.008 and P = 0,002)]. Ninety-six percent of patients and investigators for the same percentage of patients rated the tolerability of the water as "good" or "very good". CONCLUSION:The data demonstrate effectiveness of a hydrogen carbonate-rich mineral water in alleviating heartburn frequency and severity, thereby improving quality of life. The water has excellent tolerability.
| S-EPMC4753184 | biostudies-literature
Project description:Molecular hydrogen is thought to have an inhibitory effect on oxidative stress, thereby attenuating the onset and progression of various diseases including cardiovascular disease; however, few reports have assessed the preventive effect of constitutive inhalation of hydrogen gas on of vascular remodeling. Here, we investigated the effect of constitutive inhalation of hydrogen gas on vascular neointima formation using a cuff-induced vascular injury mouse model. After constitutive inhalation of compressed hydrogen gas (O2 21%, N2 77.7%, hydrogen 1.3%) or compressed air only (O2 21%, N2 79%) by C57BL/6 mice for 2 weeks from 8 weeks of age in a closed chamber, inflammatory cuff injury was induced by polyethylene cuff placement around the femoral artery under anesthesia, and hydrogen gas administration was continued until sampling of the femoral artery. Neointima formation, accompanied by an increase in cell proliferation, was significantly attenuated in the hydrogen group compared with the control group. NADPH oxidase NOX1 downregulation in response to cuff injury was shown in the hydrogen group, but the expression levels of NADPH oxidase subunits, p40phox and p47phox, did not differ significantly between the hydrogen and control groups. Although the increase in superoxide anion production did not significantly differ between the hydrogen and control groups, DNA damage was decreased as a result of reduction of reactive oxygen species such as hydroxyl radical (?OH) and peroxynitrite (ONOO-) in the hydrogen group. These results demonstrate that constitutive inhalation of hydrogen gas attenuates vascular remodeling partly via reduction of oxidative stress, suggesting that constitutive inhalation of hydrogen gas at a safe concentration in the living environment could be an effective strategy for prevention of vascular diseases such as atherosclerosis.
| S-EPMC7164592 | biostudies-literature
Project description:Upregulation of the RAS-RAF-MEK-ERK-MAPK pathway is involved in the development of several human tumors, aortic aneurysms, atherosclerosis, and cardiomyopathy. Refametinib, a highly selective MEK-inhibitor, has already shown antineoplastic activity in phase II trials. Furthermore, it showed potency to attenuate aortic root growth in murine models. Current formulations of this drug however necessitate oral gavage as a delivery method for long-term studies, which is labor-intensive and induces stress and occasional injury, potentially confounding results. Therefore, we developed a novel oral administration method for refametinib. A 2-hydroxypropyl-beta-cyclodextrin (HPBCD) based drinking water preparation of refametinib was formulated, for which a selective, analytical UHPLC-UV method was developed to assess the in-use stability. Next, 16 week old male wild-type C57Bl/6J mice received either a daily dose of 50 or 75 mg/kg/day refametinib or were given regular drinking water during 7 days. In both dosage groups the refametinib plasma levels were measured (n = 10 or 7, respectively). Furthermore, pERK/total ERK protein levels were calculated in the myocardial and aortic tissue of mice receiving a daily dose of 50 mg/kg/day refametinib and untreated mice (n = 4/group). After 7 days no significant degradation of refametinib was observed when dissolved in drinking water provided that drinking bottles were protected from UV/visible light. Furthermore, a dose-dependent increase in refametinib plasma levels was found whereby active plasma levels (> 1.2 µg/mL) were obtained even in the lowest dose-group of 50 mg/kg/day. A significant reduction of pERK/total ERK protein levels compared to untreated mice was observed in aortic and myocardial tissue of mice receiving a daily dose of 50 mg/kg/day refametinib. Importantly, a relatively high mortality rate was noted in the highest dose group (n = 5). This approach provides a valid alternative oral administration method for refametinib with a reduced risk of complications due to animal manipulation and without loss of functionality, which can be implemented in future research regarding the malignant upregulation of the RAS-RAF-MEK-ERK-MAPK pathway. However, care must be taken not to exceed the toxic dose.
| S-EPMC7483920 | biostudies-literature
Project description:Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Patients or animal models of depression show significant increase of proinflammatory cytokine interleukin-1β (IL-1β) and oxidative stress biomarkers in the periphery or central nervous system (CNS). Recent studies show that hydrogen selectively reduces cytotoxic oxygen radicals, and hydrogen-rich saline potentially suppresses the production of several proinflammatory mediators. Since current depression medications are accompanied by a wide spectrum of side effects, novel preventative or therapeutic measures with fewer side effects might have a promising future. We investigated the effects of drinking hydrogen-rich water on the depressive-like behavior in mice and its underlying mechanisms. Our study show that hydrogen-rich water treatment prevents chronic unpredictable mild stress (CUMS) induced depressive-like behavior. CUMS induced elevation in IL-1β protein levels in the hippocampus, and the cortex was significantly attenuated after 4 weeks of feeding the mice hydrogen-rich water. Over-expression of caspase-1 (the IL-1β converting enzyme) and excessive reactive oxygen species (ROS) production in the hippocampus and prefrontal cortex (PFC) was successfully suppressed by hydrogen-rich water treatment. Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.
| S-EPMC4812321 | biostudies-other