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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 attenuated neurotoxicity and behavioral phenotype induced by chronic infusion of MPTP.(A) Schedule for continuous infusion of MPTP and behavioral observation. Mice started to drink non-H2 water or H2/Mg water 1 week before infusion of minipump. The 1st open-field test was performed in the morning of pump infusion. The 2nd test was performed 28 days after pump infusion. (B) TH-staining from mice with saline-infusion drinking non-H2 water (I) or H2/Mg water (II) and those from mice with MPTP-infusion drinking non-H2 water (III) or H2/Mg water (IV). (C) Average number of TH-positive neurons in mice with saline- or MPTP-infusion (n = 6). Brain samples were obtained from six 20 µm coronal SN sections. (D) Suppression of open-field activity by chronic infusion of MPTP was partially recovered by drinking H2/Mg water. Relative ambulation score at the 2nd measurement was expressed as percentage of the 1st measurement (n = 6 for each group). 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-g005: Drinking H2/Mg water attenuated neurotoxicity and behavioral phenotype induced by chronic infusion of MPTP.(A) Schedule for continuous infusion of MPTP and behavioral observation. Mice started to drink non-H2 water or H2/Mg water 1 week before infusion of minipump. The 1st open-field test was performed in the morning of pump infusion. The 2nd test was performed 28 days after pump infusion. (B) TH-staining from mice with saline-infusion drinking non-H2 water (I) or H2/Mg water (II) and those from mice with MPTP-infusion drinking non-H2 water (III) or H2/Mg water (IV). (C) Average number of TH-positive neurons in mice with saline- or MPTP-infusion (n = 6). Brain samples were obtained from six 20 µm coronal SN sections. (D) Suppression of open-field activity by chronic infusion of MPTP was partially recovered by drinking H2/Mg water. Relative ambulation score at the 2nd measurement was expressed as percentage of the 1st measurement (n = 6 for each group). 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: Despite the lack of parkinsonian symptoms in the acute MPTP model in rodents, probably due to the low level of MAO-B in the rodent brain's capillaries [15], behavioral impairment could be observed in the chronic MPTP infusion model using an osmotic minipump to deliver the MPTP for long period [16]. This could provide a better model for human PD. In this experiment, mice were supplied with H2 water or non-H2 water 7 days prior to the pump implantation and the water supply continued until brain extirpation 28 days later (Figure 5A). Chronic infusion of MPTP induced a loss of TH-positive dopaminergic neuron in SNpc (Figure 5B). In mice drinking H2 water, the loss of TH-positive cells (76% of control: saline & non-H2 water) was less than that in mice drinking non-H2 water (56% of control: saline & non-H2 water) (Figure 5C). For the behavioral test, the ambulation scores in the open-field test were compared. Using the slightly modified open-field test reported previously [16], the ambulation score was expressed as percentage of that obtained in the first trial. Drinking H2 water did not show any significant change in the ambulation score in mice with saline infusion (69±3% with non-H2 water and 73±6% with H2 water, respectively). The ambulation score in mice with chronic MPTP infusion with non-H2 water was 40±4%, while in mice with H2 water was 54±4% (Figure 5D). Other behavioral tests, for example the rotarod test and tail suspension test, were also examined but no significant effects were observed following chronic MPTP infusion (data not shown).


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 attenuated neurotoxicity and behavioral phenotype induced by chronic infusion of MPTP.(A) Schedule for continuous infusion of MPTP and behavioral observation. Mice started to drink non-H2 water or H2/Mg water 1 week before infusion of minipump. The 1st open-field test was performed in the morning of pump infusion. The 2nd test was performed 28 days after pump infusion. (B) TH-staining from mice with saline-infusion drinking non-H2 water (I) or H2/Mg water (II) and those from mice with MPTP-infusion drinking non-H2 water (III) or H2/Mg water (IV). (C) Average number of TH-positive neurons in mice with saline- or MPTP-infusion (n = 6). Brain samples were obtained from six 20 µm coronal SN sections. (D) Suppression of open-field activity by chronic infusion of MPTP was partially recovered by drinking H2/Mg water. Relative ambulation score at the 2nd measurement was expressed as percentage of the 1st measurement (n = 6 for each group). 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-g005: Drinking H2/Mg water attenuated neurotoxicity and behavioral phenotype induced by chronic infusion of MPTP.(A) Schedule for continuous infusion of MPTP and behavioral observation. Mice started to drink non-H2 water or H2/Mg water 1 week before infusion of minipump. The 1st open-field test was performed in the morning of pump infusion. The 2nd test was performed 28 days after pump infusion. (B) TH-staining from mice with saline-infusion drinking non-H2 water (I) or H2/Mg water (II) and those from mice with MPTP-infusion drinking non-H2 water (III) or H2/Mg water (IV). (C) Average number of TH-positive neurons in mice with saline- or MPTP-infusion (n = 6). Brain samples were obtained from six 20 µm coronal SN sections. (D) Suppression of open-field activity by chronic infusion of MPTP was partially recovered by drinking H2/Mg water. Relative ambulation score at the 2nd measurement was expressed as percentage of the 1st measurement (n = 6 for each group). 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: Despite the lack of parkinsonian symptoms in the acute MPTP model in rodents, probably due to the low level of MAO-B in the rodent brain's capillaries [15], behavioral impairment could be observed in the chronic MPTP infusion model using an osmotic minipump to deliver the MPTP for long period [16]. This could provide a better model for human PD. In this experiment, mice were supplied with H2 water or non-H2 water 7 days prior to the pump implantation and the water supply continued until brain extirpation 28 days later (Figure 5A). Chronic infusion of MPTP induced a loss of TH-positive dopaminergic neuron in SNpc (Figure 5B). In mice drinking H2 water, the loss of TH-positive cells (76% of control: saline & non-H2 water) was less than that in mice drinking non-H2 water (56% of control: saline & non-H2 water) (Figure 5C). For the behavioral test, the ambulation scores in the open-field test were compared. Using the slightly modified open-field test reported previously [16], the ambulation score was expressed as percentage of that obtained in the first trial. Drinking H2 water did not show any significant change in the ambulation score in mice with saline infusion (69±3% with non-H2 water and 73±6% with H2 water, respectively). The ambulation score in mice with chronic MPTP infusion with non-H2 water was 40±4%, while in mice with H2 water was 54±4% (Figure 5D). Other behavioral tests, for example the rotarod test and tail suspension test, were also examined but no significant effects were observed following chronic MPTP infusion (data not shown).

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