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Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Tanaka Y, Nakabeppu Y, Noda M - PLoS ONE (2009)

Bottom Line: The concentration-dependency of H(2) showed that H(2) as low as 0.08 ppm had almost the same effect as saturated H(2) water (1.5 ppm).MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H(2)-containing water, whereas production of superoxide (O(2)*(-)) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly.Thus, drinking H(2)-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

ABSTRACT
It has been shown that molecular hydrogen (H(2)) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). Here, we show that drinking H(2)-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration-dependency of H(2) showed that H(2) as low as 0.08 ppm had almost the same effect as saturated H(2) water (1.5 ppm). MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H(2)-containing water, whereas production of superoxide (O(2)*(-)) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly. Our results indicated that low concentration of H(2) in drinking water can reduce oxidative stress in the brain. Thus, drinking H(2)-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.

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Drinking H2/Mg water before and after acute injection of MPTP reduced loss of dopaminergic neurons.(A) TH-positive dopaminergic neurons in SN. Mice were treated with non-H2 water or H2/Mg water before and after acute MPTP injection. Scale; 200 µm. (B) Schedule for drinking H2 water before (i) and after (ii) MPTP injection. (C) Average number of TH-positive neurons in mice with acute injection of saline or MPTP. One-way ANOVA; ###P<0.001 compared to saline with non-H2 water; *P<0.05, **P<0.01 compared to MPTP with non-H2 water. Error bars represent mean ± SEM.
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pone-0007247-g003: Drinking H2/Mg water before and after acute injection of MPTP reduced loss of dopaminergic neurons.(A) TH-positive dopaminergic neurons in SN. Mice were treated with non-H2 water or H2/Mg water before and after acute MPTP injection. Scale; 200 µm. (B) Schedule for drinking H2 water before (i) and after (ii) MPTP injection. (C) Average number of TH-positive neurons in mice with acute injection of saline or MPTP. One-way ANOVA; ###P<0.001 compared to saline with non-H2 water; *P<0.05, **P<0.01 compared to MPTP with non-H2 water. Error bars represent mean ± SEM.

Mentions: For further experiments, H2/Mg water was used, which was made by a much easier and safer procedure. H2/Mg water contained about 0.08 ppm H2. H2/Mg water showed a similar protective effect as H2-bubbled water on the loss of dopaminergic neurons in acute MPTP model mice. Without MPTP administration, H2/Mg water had no effect on the number of TH-positive cells (195±8; non-H2/Mg water, 194±4; H2/Mg water, Figure 3A, 3C). To test whether or not drinking H2/Mg water was effective even after suffering oxidative stress, we compared two different procedures (Figure 3B); one was giving H2/Mg water 7 days prior to the acute MPTP administration (Figure 3B; shown as i) and the other giving H2/Mg water only after MPTP administration (Figure 3B; shown as ii). The result showed that drinking H2/Mg water reduced the loss of dopaminergic neurons even after MPTP injection (Figure 3B, 3C; 16% & 17% recovery in drinking protocol shown as A&B, respectively). This may imply that drinking H2 water might be effective even after the onset of oxidative stress-induced PD.


Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Tanaka Y, Nakabeppu Y, Noda M - PLoS ONE (2009)

Drinking H2/Mg water before and after acute injection of MPTP reduced loss of dopaminergic neurons.(A) TH-positive dopaminergic neurons in SN. Mice were treated with non-H2 water or H2/Mg water before and after acute MPTP injection. Scale; 200 µm. (B) Schedule for drinking H2 water before (i) and after (ii) MPTP injection. (C) Average number of TH-positive neurons in mice with acute injection of saline or MPTP. One-way ANOVA; ###P<0.001 compared to saline with non-H2 water; *P<0.05, **P<0.01 compared to MPTP with non-H2 water. Error bars represent mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747267&req=5

pone-0007247-g003: Drinking H2/Mg water before and after acute injection of MPTP reduced loss of dopaminergic neurons.(A) TH-positive dopaminergic neurons in SN. Mice were treated with non-H2 water or H2/Mg water before and after acute MPTP injection. Scale; 200 µm. (B) Schedule for drinking H2 water before (i) and after (ii) MPTP injection. (C) Average number of TH-positive neurons in mice with acute injection of saline or MPTP. One-way ANOVA; ###P<0.001 compared to saline with non-H2 water; *P<0.05, **P<0.01 compared to MPTP with non-H2 water. Error bars represent mean ± SEM.
Mentions: For further experiments, H2/Mg water was used, which was made by a much easier and safer procedure. H2/Mg water contained about 0.08 ppm H2. H2/Mg water showed a similar protective effect as H2-bubbled water on the loss of dopaminergic neurons in acute MPTP model mice. Without MPTP administration, H2/Mg water had no effect on the number of TH-positive cells (195±8; non-H2/Mg water, 194±4; H2/Mg water, Figure 3A, 3C). To test whether or not drinking H2/Mg water was effective even after suffering oxidative stress, we compared two different procedures (Figure 3B); one was giving H2/Mg water 7 days prior to the acute MPTP administration (Figure 3B; shown as i) and the other giving H2/Mg water only after MPTP administration (Figure 3B; shown as ii). The result showed that drinking H2/Mg water reduced the loss of dopaminergic neurons even after MPTP injection (Figure 3B, 3C; 16% & 17% recovery in drinking protocol shown as A&B, respectively). This may imply that drinking H2 water might be effective even after the onset of oxidative stress-induced PD.

Bottom Line: The concentration-dependency of H(2) showed that H(2) as low as 0.08 ppm had almost the same effect as saturated H(2) water (1.5 ppm).MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H(2)-containing water, whereas production of superoxide (O(2)*(-)) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly.Thus, drinking H(2)-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

ABSTRACT
It has been shown that molecular hydrogen (H(2)) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). Here, we show that drinking H(2)-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration-dependency of H(2) showed that H(2) as low as 0.08 ppm had almost the same effect as saturated H(2) water (1.5 ppm). MPTP-induced accumulation of cellular 8-oxoguanine (8-oxoG), a marker of DNA damage, and 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation were significantly decreased in the nigro-striatal dopaminergic pathway in mice drinking H(2)-containing water, whereas production of superoxide (O(2)*(-)) detected by intravascular injection of dihydroethidium (DHE) was not reduced significantly. Our results indicated that low concentration of H(2) in drinking water can reduce oxidative stress in the brain. Thus, drinking H(2)-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.

Show MeSH
Related in: MedlinePlus