Original Title in Czech:
Dlouhodobá inhalace plynného vodíku u pacientů s pokročilou Alzheimerovou chorobou: kazuistika ukazující zlepšení fekální inkontinence

Authors:
Hirohisa Ono, Yoji Nishijima, Masaki Sakamoto, Soitirou Kitamura, Yuitiou Naitoh, Keiko Suzuki, Norio Fujii, Ryouta Kikura, Shigeo Ohta

Source: Medical Research Archives, Volume 10, Article No. 7 (2022)

Background

Molecular hydrogen (H₂) has emerged as a therapeutic medical gas with a variety of physiological functions. Inhalation of H₂ has been approved as safe, and several clinical studies have shown that it effectively improves conditions in patients with various disorders such as stroke, myocardial infarction, chronic obstructive pulmonary disease (COPD), cancer, and COVID-19. Urinary and fecal incontinence are inevitable symptoms of advanced Alzheimer’s disease (AD). In particular, fecal incontinence increases the level of confusion in patients and imposes a higher burden on caregivers.

Methodology

To assess the integrity of neurons affected by AD, neuronal fiber bundles passing through the hippocampus were visualized using modified diffusion tensor imaging (DTI) with advanced magnetic resonance imaging (MRI) techniques.

Výsledky

A 79-year-old woman with advanced AD inhaled 3% hydrogen gas containing 21% oxygen twice daily for one hour, and was clinically monitored over a two-year period. After long-term H₂ inhalation, the patient was able to go to the bathroom by herself to defecate adequately. Following prolonged H₂ inhalation therapy, an MRI of her brain was conducted to generate DTI images with a fractional anisotropy (FA) value of 0.2. These images demonstrated improved hippocampal neuronal integrity corresponding with the observed clinical improvements.

Citace

ONO, Hirohisa et al. Long-Term Inhalation of Hydrogen Gas for Patients with Advanced Alzheimer’s Disease: A Case Report Showing Improvement in Fecal Incontinence. Medical Research Archives, [S.l.], vol. 10, no. 7, July 2022. ISSN 2375-1924. Available at: https://esmed.org/MRA/mra/article/view/2951. Accessed: August 22, 2024.
DOI: https://doi.org/10.18103/mra.v10i7.2951

Authors:
Yoritaka, A.; Takanashi, M.; Hirayama, M.; Nakahara, T.; Ohta, S.; Hattori, N.

Source: Movement Disorders, Volume 28, Issue 6 (2013)

Background

Oxidative stress plays a significant role in the progression of Parkinson’s disease (PD). Recent studies have confirmed that molecular hydrogen (H₂) functions as a highly effective antioxidant in cultured cells and animal models. Drinking water dissolved with H₂ (H₂-water) was shown to reduce oxidative stress and improve Parkinsonian features in animal models.

Methodology

In this placebo-controlled, randomized, double-blind, parallel-group clinical pilot study, the authors evaluated the efficacy of H₂-water in Japanese patients with PD who were being treated with levodopa. Participants consumed 1,000 ml/day of either H₂-water or placebo water (sham water) for a period of 48 weeks.

Výsledky

The total Unified Parkinson’s Disease Rating Scale (UPDRS) score in the H₂-water group (n = 9) improved (median: –1.0; mean ± standard deviation: –5.7 ± 8.4), whereas the UPDRS score in the placebo group (n = 8) worsened (median: 4.5; mean ± standard deviation: 4.1 ± 9.2). Despite the small sample size and relatively short duration, the difference between groups was statistically significant (P < 0.05).

Závěr

The results demonstrated that drinking H₂-water was safe, well tolerated, and led to a statistically significant improvement in the total UPDRS score in patients with Parkinson’s disease.

Citace

Yoritaka A, Takanashi M, Hirayama M, Nakahara T, Ohta S, Hattori N. Pilot study of H₂ therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial. Mov Disord. 2013 Jun;28(6):836–839. doi: 10.1002/mds.25375. Epub 2013 Feb 11. PMID: 23400965

Authors:
Ono, H.; Nishijima, Y.; Ohta, S.

Source: Pharmaceuticals, Volume 16, Issue 3 (2023)

Background

Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disorder. Hydrogen gas (H₂) is a therapeutic medical gas with multiple functions, including antioxidant, anti-inflammatory, anti-apoptotic effects, and stimulation of energy metabolism.

Methodology

To explore the potential of H₂ as a disease-modifying treatment for AD via multifactorial mechanisms, an open-label pilot study was conducted. Eight patients with AD inhaled 3% hydrogen gas for one hour, twice daily over a period of 6 months, followed by a 1-year observation period without H₂ inhalation. Cognitive performance was assessed using the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog). To objectively evaluate neuronal integrity, diffusion tensor imaging (DTI) with advanced magnetic resonance imaging (MRI) was applied to visualize neuronal fiber bundles passing through the hippocampus.

Výsledky

The average individual change in ADAS-cog scores showed significant improvement after 6 months of H₂ treatment (–4.1), compared to untreated patients (+2.6). According to DTI assessments, H₂ therapy significantly enhanced the integrity of hippocampal neurons relative to baseline. Improvements in both ADAS-cog and DTI were sustained at the 6-month follow-up (statistically significant), and at 1-year follow-up (not statistically significant).

Závěr

This study suggests that H₂ therapy not only alleviates transient symptoms but may also exert disease-modifying effects, despite the study’s limitations.

Citace

Ono H, Nishijima Y, Ohta S. Therapeutic Inhalation of Hydrogen Gas for Alzheimer’s Disease Patients and Subsequent Long-Term Follow-Up as a Disease-Modifying Treatment: An Open Label Pilot Study. Pharmaceuticals (Basel). 2023 Mar 13;16(3):434. doi: 10.3390/ph16030434. PMID: 36986533; PMCID: PMC10057981

Authors:
Alexis R. Cole, Francesca Sperotto, James A. DiNardo, Stephanie Carlisle, Michael J. Rivkin, Lynn A. Sleeper, John N. Kheir

Source: Critical Care Explorations, Volume 3, Issue 10 (2021)

Background

Ischemia-reperfusion injury is a common condition in critically ill patients, for which no targeted therapy currently exists. Inhaled hydrogen gas has been shown to reduce ischemia-reperfusion injury in experimental models of shock, stroke, and cardiac arrest.

Cíl

The aim of this study was to investigate the safety of inhaled hydrogen gas at doses appropriate for clinical efficacy studies.

Methodology

This was a prospective, single-arm study involving eight healthy adult volunteers. Participants inhaled 2.4% hydrogen gas in medical-grade air using a high-flow nasal cannula (15 L/min) for durations of 24 (n = 2), 48 (n = 2), or 72 (n = 4) hours.

Výsledky

Monitored parameters included vital signs, patient-reported symptoms (stratified by clinical significance), pulmonary function testing, 12-lead electrocardiogram, Mini-Mental State Examination (MMSE), neurological examination, and serologic testing before and after exposure. All adverse events were reviewed by two physicians outside the study team and by an external data and safety monitoring board.
All eight participants (aged 18–30 years; 50% female; 62% non-white) completed the study without early termination. No clinically significant adverse effects were observed. Compared to baseline, no clinically significant changes were found in vital signs, pulmonary function test results, MMSE scores, neurological findings, electrocardiographic readings, or serologic markers for hematologic, renal, hepatic, pancreatic, or cardiac injury—except for a clinically insignificant increase in hematocrit and platelet count.

Závěr

Inhalation of 2.4% hydrogen gas appears not to induce clinically significant adverse effects in healthy adults. While these data suggest that inhaled hydrogen gas is well tolerated, further studies are necessary to support continued safety evaluation. These findings provide a foundation for future interventional trials investigating hydrogen gas inhalation in injury-related conditions, including cardiac arrest.

Citace

Cole AR, Sperotto F, DiNardo JA, Carlisle S, Rivkin MJ, Sleeper LA, Kheir JN. Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults. Crit Care Explor. 2021 Oct 8;3(10):e543. doi: 10.1097/CCE.0000000000000543. PMID: 34651133; PMCID: PMC8505337

Authors:
Zanini, D.; Todorovic, N.; Korovljev, D.; Stajer, V.; Ostojic, J.; Purac, J.; Kojic, D.; Vukasinovic, E.; Djordjievski, S.; Sopic, M.; Guzonjic, A.; Ninic, A.; Erceg, S.; Ostojic, S.M.

Source: Experimental Gerontology, Volume 155 (2021)

Cíl

This randomized controlled pilot study investigated the effects of six-month hydrogen-rich water (HRW) intake on multiple molecular and phenotypic biomarkers of aging in older adults aged 70 and above.

Methodology

Forty older adults (20 women) were randomly assigned to parallel groups to receive either 0.5 liters per day of HRW (15 ppm hydrogen) or a control beverage (0 ppm hydrogen) for a 6-month intervention period. Biomarkers assessed at baseline and follow-up included: blood-based molecular markers (DNA and chromosomes, nutrient sensing, protein and lipid metabolism, oxidative stress and mitochondria, cellular senescence, inflammation), brain metabolism, cognitive function, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life.
The mean age, weight, and height of participants were 76.0 ± 5.6 years, 78.2 ± 16.1 kg, and 167.5 ± 11.5 cm, respectively.

Výsledky

A significant treatment × time interaction was observed for telomere length (P = 0.049), which increased after HRW intake (from 0.99 ± 0.15 at baseline to 1.02 ± 0.26 at follow-up), while it decreased in the control group (from 0.92 ± 0.27 to 0.79 ± 0.15). Expression of the DNA methylation marker TET2 increased in both groups, but the increase was significantly greater in the HRW group (from 0.81 ± 0.52 to 1.62 ± 0.66) compared to the control (from 1.13 ± 0.82 to 1.76 ± 0.87; P = 0.040). A strong trend for interaction was observed for DNA methylation level (P = 0.166), with methylation increasing in the HRW group (from 120.6 ± 39.8 ng to 126.6 ± 33.8 ng) and decreasing in the control group (from 133.6 ± 52.9 ng to 121.2 ± 38.4 ng).
HRW also showed superior effects over the control in enhancing levels of brain choline and N-acetylaspartate (NAA) in the left frontal gray matter, brain creatine in the right parietal white matter, and brain NAA in the right parietal medial gray matter (P < 0.05). No other outcomes showed significant differences (P > 0.05), except for significantly improved chair-stand performance in the HRW group (P = 0.01).

Závěr

Due to its pleiotropic mechanisms of action, hydrogen may be recognized as a potential anti-aging agent capable of addressing several hallmarks of aging, including functional decline and telomere shortening.

Citace

Zanini D, Todorovic N, Korovljev D, Stajer V, Ostojic J, Purac J, Kojic D, Vukasinovic E, Djordjievski S, Sopic M, Guzonjic A, Ninic A, Erceg S, Ostojic SM. The effects of 6-month hydrogen-rich water intake on molecular and phenotypic biomarkers of aging in older adults aged 70 years and over: A randomized controlled pilot trial. Exp Gerontol. 2021 Nov;155:111574. doi: 10.1016/j.exger.2021.111574. Epub 2021 Oct 1. PMID: 34601077

Authors:
Mizuno, K.; Sasaki, A.T.; Ebisu, K.; Tajima, K.; Kajimoto, O.; Nojima, J.; Kuratsune, H.; Hori, H.; Watanabe, Y.

Source: Medical Gas Research, Volume 7, Issue 4 (2017)

Background

Health and a vibrant life are universally sought after. To improve quality of life (QOL), maintain health, and prevent various diseases, it is essential to evaluate the effects of factors that may enhance QOL. Chronic oxidative stress and inflammation deteriorate central nervous system function, thereby reducing QOL. In healthy individuals, factors such as aging, work-related stress, and cognitive load can elevate oxidative stress within a few hours, suggesting that preventing the accumulation of oxidative stress from daily stressors and workload is key to maintaining QOL and mitigating aging-related effects. Hydrogen has antioxidant properties and anti-inflammatory potential, and may thus contribute to QOL improvement.

Cíl

This study aimed to investigate the effects of drinking hydrogen-rich water (HRW) on the QOL of adult volunteers through psychophysiological assessments, including questionnaires, autonomic nerve function testing, and cognitive evaluations.

Metodika

In this double-blind, placebo-controlled, crossover study, 26 volunteers (13 women, 13 men; mean age 34.4 ± 9.9 years) were randomly assigned to receive either HRW (600 ml/day) or placebo water (PLW, 600 ml/day) for a 4-week period.

Výsledky

The post-/pre-treatment ratios for the K6 psychological distress scale and sympathetic nerve activity at rest were significantly lower after HRW administration compared to PLW.

Závěr

These findings suggest that HRW may enhance QOL through its effects on central nervous system functions, specifically by improving mood, reducing anxiety, and supporting autonomic nervous system regulation.

Citace

Mizuno, Kei; Sasaki, Akihiro T.; Ebisu, Kyoko; Tajima, Kanako; Kajimoto, Osami; Nojima, Junzo; Kuratsune, Hirohiko; Hori, Hiroshi; Watanabe, Yasuyoshi. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Medical Gas Research 7(4): 247–255, Oct–Dec 2017. DOI: 10.4103/2045-9912.222448

Authors:
Rahman, M.H.; Bajgai, J.; Sharma, S.; Jeong, E.S.; Goh, S.H.; Jang, Y.G.; Kim, C.S.; Lee, K.J.

Source: Antioxidants, Volume 12, Article No. 6 (2023)

Background

Molecular hydrogen (H₂) is recognized as a versatile therapeutic agent. Inhalation of hydrogen gas is considered safe and has shown positive effects in various diseases, including Alzheimer’s disease (AD).

Methodology

In this open-label, single-arm prospective study, 54 community-dwelling adults aged 40–70 years underwent H₂ gas inhalation therapy for 4 weeks. The study evaluated:

• Total and differential white blood cell (WBC) counts,

• Levels of reactive oxygen and nitrogen species (ROS/RNS),

• Activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE-1),

• Brain-derived neurotrophic factor (BDNF),

• Dementia-related biomarkers including amyloid-beta peptides (Aβ), vascular endothelial growth factor A (VEGF-A), total tau (T-tau), monocyte chemoattractant protein-1 (MCP-1), and the inflammatory cytokine interleukin-6 (IL-6).

Výsledky

There were no adverse effects on total or differential WBC counts following H₂ gas inhalation, indicating good safety and tolerability. Levels of oxidative stress markers (such as ROS and nitric oxide) were significantly reduced post-treatment. Furthermore, assessment of dementia-related biomarkers—including BACE-1, Aβ peptides, BDNF, VEGF-A, T-tau, MCP-1, and IL-6—demonstrated marked improvements in cognitive parameters in most participants after treatment.

Závěr

These findings suggest that hydrogen gas inhalation may be a promising therapeutic option for improving cognitive function in adults of varying ages with Alzheimer-like cognitive impairment living in community settings.

Citace

Rahman MH, Bajgai J, Sharma S, Jeong ES, Goh SH, Jang YG, Kim CS, Lee KJ. Effects of Hydrogen Gas Inhalation on Community-Dwelling Adults of Various Ages: A Single-Arm, Open-Label, Prospective Clinical Trial. Antioxidants (Basel). 2023 Jun 8;12(6):1241. doi: 10.3390/antiox12061241. PMID: 37371971; PMCID: PMC10295751

Authors:
Hong, C.T.; Hu, C.J.; Lin, H.Y.; Wu, D.

Source: Medicine (Baltimore), Volume 100, Article No. 4 (2021)

Background

Parkinson’s disease (PD), the second most common neurodegenerative disorder, currently has no cure or established disease-modifying therapies—only symptomatic treatment is available. Oxidative stress and mitochondrial dysfunction are key factors in PD pathophysiology. Animal studies have shown that photobiomodulation (PBM) can enhance mitochondrial function and increase ATP production, thereby alleviating PD symptoms; however, this process may also elevate the production of reactive oxygen species (ROS).
Molecular hydrogen (H₂) is a potent and potentially therapeutic antioxidant capable of neutralizing ROS. Targeting the brainstem with PBM may facilitate neuronal activity, while concurrent H₂ administration may eliminate excess ROS generated by PBM. Therefore, this study aimed to evaluate the safety and efficacy of combined PBM and H₂ therapy in PD patients.

Metodika

A total of 18 patients with PD (aged 30–80 years), classified as stage II–III according to the Hoehn and Yahr scale, were enrolled in the study. All participants underwent daily PBM + H₂ therapy for 2 weeks. Adverse events and Unified Parkinson Disease Rating Scale (UPDRS) scores were recorded throughout the study.

Výsledky

UPDRS scores began to significantly decrease from the first week of treatment, and improvements were maintained through the end of the two-week intervention. No adverse events were reported. One week after discontinuing therapy, UPDRS scores slightly increased, but the improvements remained significant compared to baseline.

Závěr

This pilot study demonstrated that combined PBM + H₂ therapy is safe and can reduce disease severity in patients with PD. A larger clinical trial is planned to further investigate the therapeutic potential of this combined approach.

Citace

Hong CT, Hu CJ, Lin HY, Wu D. Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study. Medicine (Baltimore). 2021 Jan 29;100(4):e24191. doi: 10.1097/MD.0000000000024191. PMID: 33530211; PMCID: PMC7850666

Authors:
Yuan, J.; Wang, D.F.; Liu, Y.; Chen, X.J.; Zhang, H.L.; Shen, F.; Liu, X.; Fu, J.Q.

Source: Journal of Surgical Research, Volume 228, Pages 238–246 (2018)

Background

Recent studies have shown that oxidative stress plays a key role in the pathogenesis of traumatic brain injury (TBI) and may serve as a target in its treatment. Hydrogen-rich water (HRW), due to its antioxidant properties, has demonstrated neuroprotective effects in various neurological conditions. However, the mechanisms underlying its impact on TBI remain insufficiently understood.

Cíl

This study aimed to evaluate the neuroprotective role of HRW in rats with TBI and to elucidate the possible mechanisms behind its effects, particularly with respect to the Nrf2 signaling pathway.

Metodika

TBI was induced using a modified Feeney weight-drop method. In the first experimental phase, oxidative stress markers were assessed by measuring the expression levels of catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA). Nuclear factor erythroid 2–related factor 2 (Nrf2) levels were evaluated to determine its role in HRW’s neuroprotective effects.
In the second phase, the neuroprotective effects of HRW and its impact on Nrf2 activation were further confirmed. Rats were randomly assigned into three groups: Sham, TBI, and TBI + HRW. Twenty rats from each group were monitored for 7-day survival. Neurological severity scores were recorded for six rats per group, which were then sacrificed 24 hours after testing. Spectrophotometry was used to measure GPx, CAT, and MDA levels. Western blotting, RT-PCR, and immunohistochemistry were employed to measure the expression of Nrf2 and downstream effectors such as heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1).

Výsledky

GPx and CAT activities were significantly reduced, while MDA levels were elevated in the TBI group compared to the sham group at 6 hours post-injury, peaking at 24 hours. Nuclear Nrf2 protein levels increased significantly after TBI, peaking at 24 hours, although no significant changes in Nrf2 mRNA expression were observed. HRW treatment significantly improved 7-day survival, reduced neurological deficits, and lowered intracellular oxidative stress. Furthermore, HRW facilitated Nrf2 nuclear translocation, leading to upregulation of downstream antioxidant proteins HO-1 and NQO1.

Závěr

These findings indicate that hydrogen-rich water exerts neuroprotective effects against TBI by reducing oxidative stress and activating the Nrf2 signaling pathway, suggesting its therapeutic potential in brain injury management.

Citace

Yuan, J., Wang, D., Liu, Y., Chen, X., Zhang, H., Shen, F., … & Fu, J. (2018). Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway. Journal of Surgical Research, 228, 238–246. https://doi.org/10.1016/j.jss.2018.03.015

Authors:
Han, L.; Tian, R.F.; Yan, H.H.; Pei, L.; Hou, Z.G.; Hao, S.Y.; Li, Y.V.; Tian, Q.; Liu, B.Y.; Zhang, Q.

Source: Brain Research, Volume 1615, Pages 129–138 (2015)

Background

Hydrogen-rich water (HRW) possesses antioxidant properties and exhibits neuroprotective effects during cerebral ischemia-reperfusion injury. Parvalbumin and hippocalcin are two calcium-buffering proteins involved in neuronal differentiation, maturation, and apoptosis.

Cíl

This study aimed to determine whether HRW can modulate the expression of parvalbumin and hippocalcin during ischemic brain injury and neuronal cell death caused by glutamate toxicity.

Metodika

Focal cerebral ischemia was induced in male Sprague-Dawley rats via middle cerebral artery occlusion (MCAO). Rats were treated with either distilled water or HRW (6 ml/kg per rat) before and after MCAO. Cortical brain tissues were collected at 1, 7, and 14 days post-occlusion.

Výsledky

HRW treatment significantly reduced infarct volume and improved neurological function following ischemic brain injury. Additionally, HRW prevented the ischemia-induced reduction in parvalbumin and hippocalcin levels in vivo. It also reduced glutamate-induced neuronal cell death and showed a dose-dependent suppression of glutamate toxicity-associated proteins in vitro. Furthermore, HRW attenuated the glutamate-induced rise in intracellular Ca²⁺ levels.

Závěr

These results suggest that HRW may confer neuroprotection against ischemic brain injury. The maintenance of parvalbumin and hippocalcin levels by HRW during ischemic events may contribute to its protective effects against neuronal damage.

Citace

Han, L., Tian, R., Yan, H., Pei, L., Hou, Z., Hao, S., … & Zhang, Q. (2015). Hydrogen-rich water protects against ischemic brain injury in rats by regulating calcium buffering proteins. Brain Research, 1615, 129–138. https://doi.org/10.1016/j.brainres.2015.03.044

Authors:
Zhao, M.; Liu, M.D.; Pu, Y.Y.; Wang, D.; Xie, Y.; Xue, G.C.; Jiang, Y.; Yang, Q.Q.; Sun, X.J.; Cao, L.

Source: Journal of Neuroimmunology, Volume 294, Pages 6–13 (2016)

Background

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The high cost, inconvenient administration, and adverse effects of current FDA-approved treatments often lead to poor adherence to long-term MS therapy. Molecular hydrogen (H₂) has demonstrated antioxidant, anti-apoptotic, anti-inflammatory, anti-allergic, and anticancer properties.

Methodology

This study investigated both the prophylactic and therapeutic effects of hydrogen-rich water (HRW) on the progression of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS.

Výsledky

Prophylactic administration of HRW at both 0.36 mM and 0.89 mM concentrations delayed EAE onset and reduced peak clinical severity scores. Furthermore, treatment with 0.89 mM HRW after disease onset reduced disease severity, CNS infiltration, and demyelination. HRW also inhibited CNS infiltration by CD4⁺ T lymphocytes and suppressed the development of Th17 cells, while leaving Th1 cell populations unaffected.
Importantly, HRW is non-toxic, cost-effective, easily administered, and capable of crossing the blood-brain barrier.

Závěr

These results suggest that HRW holds strong therapeutic potential for the treatment of multiple sclerosis.

Citace

Zhao, M., Liu, M.D., Pu, Y.Y., Wang, D., Xie, Y., Xue, G.C., … & Cao, L. (2016). Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. Journal of Neuroimmunology, 294, 6–13. https://doi.org/10.1016/j.jneuroim.2016.03.009

Authors:
Li, L.T.; Liu, T.T.; Liu, L.; Li, S.C.; Zhang, Z.; Zhang, R.S.; Zhou, Y.J.; Liu, F.L.

Source: Journal of Bioenergetics and Biomembranes, Volume 51, Issue 6, Pages 393–402 (2019)

Cíl

This study examined the effects of hydrogen-rich water (HRW) on oxidative stress through the activation of the Nrf2/ARE signaling pathway in a rat model of myocardial ischemia-reperfusion injury (MIRI).

Methodology

Sixty rats were randomly assigned to either a hydrogen-rich water group or a control group (30 rats each). Each group was further divided into three subgroups: pre-ischemic phase, ischemic phase, and reperfusion phase. After the hearts were excised, they were mounted on a Langendorff apparatus and perfused with oxygenated perfusate at 37°C. The control group received Krebs–Ringer (K–R) solution, while the HRW group was perfused with K–R solution containing hydrogen-rich water.
Expression levels of mRNA and protein for Nrf2, NQO1, HO-1, and SOD-1 in cardiomyocytes were measured using RT-qPCR, immunohistochemistry (IHC), and Western blot analysis. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were also assessed.

Výsledky

HRW significantly enhanced the activation of the Nrf2/ARE pathway, with increased mRNA and protein levels of Nrf2, NQO1, HO-1, and SOD-1 during the ischemia-reperfusion phase compared to the ischemic phase (P < 0.05). In contrast, these levels were significantly reduced in the control group during reperfusion compared to ischemia.
During the ischemia-reperfusion phase, the HRW group exhibited significantly elevated SOD activity and reduced MDA content, while the control group showed decreased SOD activity and increased MDA levels (P < 0.05).

Závěr

Hydrogen-rich water may alleviate myocardial ischemia-reperfusion injury by activating the Nrf2/ARE signaling pathway and reducing oxidative stress in myocardial tissues.

Citace

Li, L., Liu, T., Liu, L., et al. (2019). Effect of hydrogen-rich water on the Nrf2/ARE signaling pathway in rats with myocardial ischemia-reperfusion injury. Journal of Bioenergetics and Biomembranes, 51(6), 393–402. https://doi.org/10.1007/s10863-019-09814-7

Authors:
Liu, Y.; Wang, D.F.; Chen, X.J.; Yuan, J.; Zhang, H.L.; Fu, J.Q.; Wang, Y.; Lan, Q.

Source: International Journal of Clinical and Experimental Pathology, Volume 10, Issue 3, Pages 3807–3815 (2017)

Background

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide and results in severe long-term disabilities.

Cíl

This study aimed to evaluate the effect of hydrogen-rich water (HRW) on angiogenesis in the brain tissue surrounding lesions in rats subjected to TBI.

Methodology

Fifty-four adult male Sprague-Dawley rats were randomly assigned to three groups: sham-operated, TBI, and TBI + HRW. After inducing TBI, neurological severity scores (NSS) were assessed. Hematoxylin-eosin staining, immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction (RT-PCR) were used to analyze brain tissue at various time points post-injury.

Výsledky

On days 3 and 7 post-injury, NSS scores in the TBI + HRW group were significantly lower compared to the TBI group (P < 0.05). At 24 hours and 3 days post-injury, histopathological analysis of the lesion boundary tissue in TBI rats revealed hemorrhagic necrosis, severe brain edema, and disrupted neuronal architecture, with the most pronounced changes observed on day 3. Compared to the TBI group, the TBI + HRW group had reduced brain edema. On day 7, neonatal capillary hyperplasia was significantly greater in the TBI + HRW group than in the TBI group (P < 0.01).
At all time points, expression levels of HIF-1α and VEGF protein and mRNA were significantly higher in the TBI + HRW group than in the TBI group (P < 0.01 / P < 0.05), and both were significantly higher than in the sham group (P < 0.01).

Závěr

Hydrogen-rich water promotes angiogenesis and improves neurological function following TBI by upregulating HIF-1α and VEGF expression. These findings suggest HRW as a promising adjunct for enhancing brain repair after injury.

Citace

Liu, Y., Wang, D., Chen, X., Yuan, J., Zhang, H., Fu, J., … & Lan, Q. (2017). Effect of hydrogen-rich water on the angiogenesis in lesion boundary brain tissue of traumatic brain injury-challenged rats. International Journal of Clinical and Experimental Pathology, 10, 3807–3815.

Authors:
Martínez-Serrat, M.; Martínez-Martel, I.; Coral-Pérez, S.; Bai, X.; Batallé, G.; Pol, O.

Source: Antioxidants, Volume 11, Issue 9 (2022), Article 1826

Background

Neuropathic pain, characterized by allodynia and hyperalgesia, often becomes a chronic condition accompanied by affective disorders such as anxiety and depression. Existing clinical treatments for neuropathic pain are often inadequate and associated with significant side effects. Recent studies highlight the protective role of molecular hydrogen (H₂) in various diseases, including neurological disorders such as Alzheimer’s disease, as well as its antidepressant effects in animal models under chronic stress.

Cíl

This study aimed to investigate the effects of hydrogen-rich water (HRW) treatment on male mice suffering from chronic constriction injury (CCI)-induced neuropathic pain and the associated affective deficits.

Methodology

The study evaluated potential pathways involved in the analgesic activity of HRW and examined the interaction between the enzyme heme oxygenase-1 (HO-1) and H₂ during neuropathic pain conditions.

Výsledky

Repeated HRW administration produced significant inhibitory effects on CCI-induced allodynia and hyperalgesia. It also demonstrated anxiolytic and antidepressant effects in mice with neuropathic pain. Key contributors to HRW’s antinociceptive activity included antioxidant enzymes (HO-1 and NAD(P)H:quinone oxidoreductase 1) and ATP-sensitive potassium channels. A positive interaction was observed between the HO-1 system and H₂ in suppressing neuropathic pain caused by CCI. Additionally, HRW exhibited antioxidant, antinociceptive, anti-inflammatory, and/or anti-apoptotic effects in the dorsal root ganglia and/or the amygdala of mice with sciatic nerve injury.

Závěr

This study reveals new neuroprotective properties of molecular hydrogen and suggests that hydrogen-rich water may offer a promising therapeutic approach for managing chronic neuropathic pain and its associated mood disorders.

Citace

Martínez-Serrat M, Martínez-Martel I, Coral-Pérez S, Bai X, Batallé G, Pol O. Hydrogen-Rich Water as a Novel Therapeutic Strategy for the Affective Disorders Linked with Chronic Neuropathic Pain in Mice. Antioxidants. 2022; 11(9):1826. https://doi.org/10.3390/antiox11091826

Authors:
Zhang, Y.; Su, W.J.; Chen, Y.; Wu, T.Y.; Gong, H.; Shen, X.L.; Wang, Y.X.; Sun, X.J.; Jiang, C.L.

Source: Scientific Reports, Volume 6, Article 23742 (2016)

Background

Emerging evidence suggests that neuroinflammation and oxidative stress are major contributors to major depressive disorder (MDD). Patients and animal models of depression often show elevated levels of the pro-inflammatory cytokine interleukin-1 beta (IL-1β) and oxidative stress markers in both the peripheral and central nervous systems (CNS). Recent studies have demonstrated that molecular hydrogen selectively reduces cytotoxic oxygen radicals and that hydrogen-rich saline can suppress the production of various pro-inflammatory mediators. Given the broad side effects associated with current antidepressant medications, new preventive or therapeutic strategies with fewer adverse effects are of considerable interest.

Methodology

This study investigated the effects of hydrogen-rich water (HRW) consumption on depressive-like behavior in mice and explored the underlying mechanisms.

Výsledky

The findings demonstrated that HRW intake prevented the development of depressive-like behavior induced by chronic unpredictable mild stress (CUMS). CUMS exposure led to increased levels of IL-1β protein in the hippocampus and cortex, which were significantly reduced after 4 weeks of HRW administration. Additionally, the overexpression of caspase-1 (an enzyme responsible for IL-1β activation) and the excessive production of reactive oxygen species (ROS) in the hippocampus and prefrontal cortex were successfully suppressed by HRW treatment.

Závěr

These results suggest that the antidepressant-like effects of hydrogen-rich water may be mediated by the suppression of inflammasome activation, leading to reduced production of IL-1β and ROS.

Citace

Zhang, Y., Su, W.J., Chen, Y., et al. (2016). Effects of hydrogen-rich water on depressive-like behavior in mice. Scientific Reports, 6, 23742. https://doi.org/10.1038/srep23742

Authors:
Tian, Y.; Guo, S.B.; Zhang, Y.; Xu, Y.; Zhao, P.; Zhao, X.C.

Source: Molecular Neurobiology, Volume 54, Issue 4, Pages 2579–2584 (2017)

Cíl

This study aimed to explore the protective effects and underlying mechanisms of hydrogen-rich saline (HRS) on cognitive function in aged mice with postoperative cognitive dysfunction (POCD) induced by partial hepatectomy.

Methodology

Ninety-six aged male Kunming mice were randomly assigned into four groups (n = 24 each):

• Control group (C),

• Hydrogen-rich saline group (H),

• POCD group (P),

• POCD + Hydrogen-rich saline group (PH).

Cognitive performance was assessed using the Morris water maze (MWM). Levels of TNF-α and IL-1β were measured by ELISA and immunohistochemistry, and NF-κB activity was assessed via ELISA. Hippocampal tissue morphology was examined using hematoxylin-eosin (HE) staining.

Výsledky

Learning and memory abilities were significantly impaired on days 10 and 14 post-surgery in the POCD group. Partial hepatectomy significantly increased escape latency, and decreased time spent in the target quadrant and platform-crossing frequency compared to controls (p < 0.05).
Surgical intervention also increased levels of TNF-α, IL-1β, and NF-κB activity at all measured time points (p < 0.05).
Treatment with hydrogen-rich saline (group PH) partially restored spatial memory and learning by reducing escape latency and increasing the time and frequency of crossing the target platform compared to the POCD group (p < 0.05).
Additionally, HRS significantly reduced hippocampal levels of TNF-α, IL-1β, and NF-κB activity (p < 0.05), and alleviated hepatectomy-induced cellular necrosis in the hippocampus.

Závěr

Hydrogen-rich saline may alleviate POCD by inhibiting NF-κB activity and suppressing the inflammatory response in the hippocampus.

Citace

Tian, Y., Guo, S., Zhang, Y., et al. (2017). Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice. Molecular Neurobiology, 54, 2579–2584. https://doi.org/10.1007/s12035-016-9825-2

Authors:
Hou, Z.G.; Luo, W.; Sun, X.J.; Hao, S.Y.; Zhang, Y.; Xu, F.F.; Wang, Z.C.; Liu, B.Y.

Source: Brain Research Bulletin, Volume 88, Issue 6, Pages 560–565 (2012)

Background

Oxidative stress is a major factor in traumatic brain injury (TBI), initiating processes that lead to prolonged neuronal dysfunction and remodeling. Importantly, antioxidants have the potential to protect the brain from oxidative damage and modulate its capacity to adapt to synaptic dysfunction and cognitive impairments. However, no prior studies had investigated the effects of hydrogen-rich saline (HRS) on cognitive deficits following TBI.

Methodology

This study utilized a rat model of fluid percussion injury (FPI) to evaluate the neuroprotective effects of hydrogen-rich saline.

Výsledky

Administration of HRS significantly reduced malondialdehyde (MDA) levels—a marker of lipid peroxidation—and increased levels of the silent information regulator 2 (Sir2). Furthermore, HRS enhanced the expression of molecules associated with synaptic plasticity mediated by brain-derived neurotrophic factor (BDNF), leading to improved cognitive performance in the Morris water maze following mild TBI.

Závěr

These findings suggest that hydrogen-rich saline can protect the brain from the deleterious effects of mild TBI on synaptic plasticity and cognition. HRS may serve as an effective therapeutic strategy for patients experiencing cognitive impairment after TBI.

Citace

Hou Z, Luo W, Sun X, Hao S, Zhang Y, Xu F, Wang Z, Liu B. Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Res Bull. 2012 Sep 1;88(6):560–565. https://doi.org/10.1016/j.brainresbull.2012.06.006. PMID: 22742936

Authors:
Lin, Y.T.; Shi, Q.Q.; Zhang, L.; Yue, C.P.; He, Z.J.; Li, X.X.; He, Q.J.; Liu, Q.; Du, X.B.

Source: Neural Regeneration Research, Volume 17, Issue 2, Pages 409–417 (2022)

Background

Hydrogen has shown therapeutic potential for Alzheimer’s disease (AD). Previous approaches involved stereotactic injection as an invasive method for delivering active hydrogen, which poses limitations for clinical applications.

Methodology

In this study, triple-transgenic (3xTg) mice with Alzheimer’s disease were treated with hydrogen-rich water (HRW) for seven months.

Výsledky

Treatment with HRW prevented synaptic loss and neuronal death, inhibited senile plaque formation, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3xTg AD mice. Furthermore, HRW improved disturbances in brain energy metabolism, corrected imbalances in gut microbiota, and attenuated neuroinflammatory responses.

Závěr

These findings suggest that hydrogen-rich water acts as an effective hydrogen donor and holds therapeutic promise for treating Alzheimer’s disease.
The study was approved by the Ethics and Animal Welfare Committee of Shenzhen University, China (Approval No. AEWC-20140615-002) on June 15, 2014.

Citace

Lin, Y.-T., Shi, Q.-Q., Zhang, L., Yue, C.-P., He, Z.-J., Li, X.-X., He, Q.-J., Liu, Q., & Du, X.-B. (2022). Hydrogen-rich water ameliorates neuropathological impairments in a mouse model of Alzheimer’s disease through reducing neuroinflammation and modulating intestinal microbiota. Neural Regeneration Research, 17(2), 409–417. https://doi.org/10.4103/1673-5374.317992

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