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Effects of hydrogen-rich water on depressive-like behavior in mice.

ABSTRACT: 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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4812321 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Effects of hydrogen-rich water on aging periodontal tissues in rats.

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

Anti-oxidant and anti-inflammatory effects of hydrogen-rich water alleviate ethanol-induced fatty liver in mice.

Project description:To investigate the effects of hydrogen-rich water (HRW) treatment on prevention of ethanol (EtOH)-induced early fatty liver in mice.In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control, EtOH, EtOH + silymarin, EtOH + HRW and EtOH + silymarin + HRW. Each group was fed a Lieber-DeCarli liquid diet containing EtOH or isocaloric maltose dextrin (control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic EtOH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 mL/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 wk.The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin, which was correlated with food intake. HRW treatment significantly reduced EtOH-induced increases in serum alanine aminotransferase, aspartate aminotransferase, triglycerol and total cholesterol levels, hepatic lipid accumulation and inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. HRW attenuated malondialdehyde level, restored glutathione depletion and increased superoxide dismutase, glutathione peroxidase and catalase activities in the liver. Moreover, HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 levels.HRW protects against chronic EtOH-induced liver injury, possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22, thus activating antioxidant enzymes against oxidative stress.

| S-EPMC5526762 | biostudies-other

Effects of hydrogen-rich water in a rat model of polycystic kidney disease.

Project description:Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.

| S-EPMC6478309 | biostudies-literature

Gene expression profiling in mouse livers after administration of both hydrogen-rich water and hydrogen gas

2014-08-01 | GSE48826 | GEO

Hydrogen-rich water ameliorates rat placental stress induced by water restriction.

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

Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL receptor-deficient mice.

Project description:The main cause of arteriosclerosis is atherosclerosis in the aorta. Atherosclerosis is recognized as a chronic inflammatory condition that begins with the dysfunction or activation of arterial endothelium. Low-density lipoprotein (LDL) and especially its oxidized form play a key role in endothelial dysfunction and atherogenesis. Recent studies showed that senescent cells are involved in the development and progression of atherosclerosis, and eliminating senescent cells suppresses the senescence-associated secretory phenotype. We previously reported that molecular hydrogen-rich water (HW) has antioxidant and anti-inflammatory effects in numerous diseases. Here, we used LDL receptor-deficient mice fed a high-fat diet (HFD) for 13 weeks as a model for atherosclerosis and evaluated the effects of continuous administration of HW. The numbers of endothelial cells in the atheroma expressing the senescence factors p16INK4a and p21 decreased in HFD-fed mice given HW compared with HFD-fed mice given control water. Furthermore, macrophage infiltration and Tnfα expression in the atheroma were also suppressed. These results suggest that vascular aging can be suppressed by HW.

| S-EPMC6235982 | biostudies-literature

Gene expression profiling in mouse livers after administration of both hydrogen-rich water and hydrogen gas

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

The Therapeutic Effects of Oral Intake of Hydrogen Rich Water on Cutaneous Wound Healing in Dogs.

Project description:This study explored the effects of drinking Hydrogen-rich water (HRW) on skin wound healing in dogs. Eight circular wounds were analyzed in each dog. The experimental group was treated with HRW thrice daily, while the control group was provided with distilled water (DW). The wound tissues of dogs were examined histopathologically. The fibroblasts, inflammatory cell infiltration, the average number of new blood vessels, and the level of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the skin homogenate of the wound was measured using the corresponding kits. The expressions of Nrf-2, HO-1, NQO-1, VEGF, and PDGF were measured using the real-time fluorescence quantitative method. We observed that HRW wounds showed an increased rate of wound healing, and a faster average healing time compared with DW. Histopathology showed that in the HRW group, the average thickness of the epidermis was significantly lower than the DW group. The average number of blood vessels in the HRW group was higher than the DW group. The MDA levels were higher in the DW group than in the HRW group, but the SOD levels were higher in the HRW group than in the DW group. The results of qRT-PCR showed that the expression of each gene was significantly different between the two groups. HRW treatment promoted skin wound healing in dogs, accelerated wound epithelization, reduced inflammatory reaction, stimulated the expression of cytokines related to wound healing, and shortened wound healing time.

| S-EPMC8618955 | biostudies-literature

Expression data from mice liver drinking Hydrogen water

Project description:Liver RNA samples from C57BL6 mice drinking Hydrogen water for 4 weeks We used microarrays to detail the gene expression after drinking hydrogen water.

2017-09-19 | GSE103941 | GEO

Effects of molecular hydrogen-dissolved alkaline electrolyzed water on intestinal environment in mice.

Project description:Increasing evidence indicates that molecular hydrogen-dissolved alkaline electrolyzed water (AEW) has various physiological activities such as antioxidative activity. Gut microbiota are deeply associated with our health through a symbiotic relationship. Recent reports have described that most gastrointestinal microbial species encode the genetic capacity to metabolize molecular hydrogen, meaning that molecular hydrogen might affect the gut microbial composition. Nevertheless, AEW effects on gut microbiota remain unknown. This study investigated AEW effects on the intestinal environment in mice, including microbial composition and short-chain fatty acid contents. After mice were administered AEW for 4 weeks, 16S rRNA gene sequencing analyses revealed their fecal microbiota profiles. Organic acid concentrations in cecal contents were measured using an HPLC system. Compared to the control group, AEW administration mice had significantly lower serum low-density lipoprotein cholesterol level and alanine aminotransferase activity. Organic acid concentrations of propionic, isobutyric, and isovaleric acids were higher in AEW-administered mice. Results of 16S rRNA gene sequencing analyses showed that the relative abundances of 20 taxa differed significantly in AEW-administered mice. Although the definitive role of gut microbes of AEW-administered mice remains unknown, our data demonstrate the possibility that AEW administration affects the gut microbial composition and that it has beneficial health effects in terms of cholesterol metabolism and liver protection.

| S-EPMC5937304 | biostudies-literature

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