No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Recent Advances in Hydrogen Research as a Therapeutic Medical Gas
Abstract
Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory and anti-apoptotic protective effects on cells and organs. Therapeutic hydrogen has been applied by different delivery methods including straightforward inhalation, drinking hydrogen dissolved in water and injection with hydrogen-saturated saline. This review summarizes currently available data regarding the protective role of hydrogen, provides an outline of recent advances in research on the use of hydrogen as a therapeutic medical gas in diverse models of disease and discusses the feasibility of hydrogen as a therapeutic strategy. It is not an overstatement to say that hydrogen's impact on therapeutic and preventive medicine could be enormous in the future.
... The latest findings in medical research regarding hydrogen unequivocally highlight substantial prospects for harnessing hydrogen as a therapeutic intervention. Extensive observations in both clinical and experimental studies distinctly demonstrate that hydrogen holds significant promise as an innovative therapy to address unmet patient needs across various etiologies [1][2][3][4][5][6][7][8][9][10]. Renowned for its antioxidant properties, hydrogen gas has emerged as a novel therapeutic agent with potential applications in various medical domains, including transplantation. ...
... While data support the use o practices, transplant surgeons cann even critically ill transplant patient tients. Further studies, including w detailed mechanisms, are required into transplantation protocols [75,7 and IL-2 [28]. The hydrogen-related advantages described herein might hold significant implications for donors, grafts/organs, and recipients, manifesting anticipated organ-protective effects ( Figure 1). ...
... While data support the use o practices, transplant surgeons cann even critically ill transplant patien tients. Further studies, including w detailed mechanisms, are required into transplantation protocols [75,7 The ability to administer me highly attractive for translation in mental oxygen are already being ad ical gas treatment via inhalation c gies by incorporating the gas into reactivity with other gases at the alongside other therapeutic gases, bined gas therapy. Recent research gen and carbon monoxide (CO) en in preventing cold IRI after heart and antioxidant mechanisms [33]. ...
Hydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen’s capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation.
... However, oxygen therapy might cause the accumulation of distal bronchial viscous secretions because of positive pressure ventilation mode, and thus increase airway resistance, aggravate systemic hypoxia [15]. In recent years, molecular hydrogen treatment has the potential to preventive and therapeutic applications against many diseases due to its extensive effects, such as antioxidant, anti-inflammatory, antiapoptotic [16,17]. More importantly, the small molecular properties of hydrogen enable it can rapidly reaches the alveoli, suggest a unique advantage for lung disease [18]. ...
... In the entire matched group, the median length of hospitalization for patients who inhaled hydrogen/oxygen were 12 days (95% CI, [9][10][11][12][13][14][15] and patients who inhaled oxygen were 13 days (95% CI, [11][12][13][14][15][16][17][18][19][20], with a HR of 1.91 (95% CI, 1.25-2.92; p < 0.05; Fig. 2). ...
... The length of hospitalization in unmatched patients from real-world setting and 1:1 matched patients were also analyzed as sensitivity analysis. The 4.5-day shorten with hydrogen/ oxygen therapy was observed in the real-world data from all unmatched patients (11.5 days [95%CI: [10][11][12][13] vs. 16 days [95%CI: [14][15][16][17][18]; p < 0.001; Additional file 1: Fig. S1A) and 2-day shorten in the 1:1 matched patients (12 days [95%CI: [9][10][11][12][13][14] vs. 14 days [95%CI: [11][12][13][14][15][16]; p = 0.019; Additional file 1: Fig. S1B). ...
Background
Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates.
Methods
This retrospective, propensity-score matched (PSM) case–control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed.
Results
Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25–2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9–15) versus the oxygen group (13 days; 95% CI, 11–20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days).
Conclusion
This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.
... Zauważając jego charakterystyczne właściwości, Henry Cavendish określił wodór mianem "zapalnego powietrza". Oficjalnie nazwano go wodorem w 1783 roku, korzystając z połączenia greckich słów hydro (woda) i genes (tworzący) [1]. ...
... Wyniki badań eksperymentalnych i klinicznych potwierdzają, że wodór może pełnić rolę antyoksydantu, chroniąc komórki, tkanki i narządy przed uszkodzeniami wywołanymi stresem oksydacyjnym poprzez efektywne usuwanie reaktywnych form tlenu [1,17]. ...
Hydrogen, a two-atom gas with unique properties such as colourlessness, odourlessness and non-metallicity, has gained significant interest due to its potential therapeutic applications. Due to its small molecular size, it is an effective antioxidant, capable of neutralizing reactive oxygen species (ROS). The aim of the article was to present methods for the application of molecular hydrogen in cosmetology, especially in hydrogen purification treatments. Its positive effects on reducing skin rashes, increasing hydration and reducing excessive sebum secretion especially in people with acne vulgaris were presented. Hydrogen shows promise as a therapeutic agent in the context of oxidative stress, which disrupts normal skin function and accelerates the ageing process. Molecular hydrogen’s adaptability makes it highly attractive for use in several therapeutic applications within the fields of medicine and cosmetology.
... By selectively decreasing hydroxyl radical (OH) and peroxynitrite anion, the breathed hydrogen displayed antioxidant and anti-apoptotic characteristics, protecting the brain against ischemia/reperfusion (I/R) injury [3]. Subsequently, the application of hydrogen as an emerging therapeutic method in many diseases, especially due to its anti-apoptosis and anti-oxidation properties has gained significant attention [4]. Hydrogen plays a crucial role in protecting different tissues and organs from antioxidant damage [4]. ...
... Subsequently, the application of hydrogen as an emerging therapeutic method in many diseases, especially due to its anti-apoptosis and anti-oxidation properties has gained significant attention [4]. Hydrogen plays a crucial role in protecting different tissues and organs from antioxidant damage [4]. In periodontal tissues, host cells produce reactive oxygen species (ROS) as part of their defense response [5]. ...
Background: Due to its antioxidant and anti-inflammatory effects, hydrogen-rich water has been used to reduce inflammatory responses in many inflammatory diseases. However, its efficacy in treating peri-implantitis remains unclear. This study aims to investigate the efficacy of hydrogen-rich water in reducing inflammatory responses in experimental peri-implantitis. Methods: A ligature-induced experimental peri-implantitis model was established using three Beagle dogs (n = 24 implants). The implants were divided into two groups: a hydrogen-rich water-treated group (n = 12 implants), and a non-treated control group (n = 12 implants). The clinical indices, including the gingival index (GI), modified sulcus bleeding index (mSBI), and probing depth (PD), were examined. Hematoxylin and eosin (H&E) staining was used to assess the inflammatory cell infiltrate in the peri-implant tissue. Additionally, three host-derived pro-inflammatory cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), and matrix metalloproteinase-8 (MMP-8) were assessed using enzyme-linked immunosorbent assay (ELISA). Furthermore, microbial community profiles were analyzed using high-throughput sequencing (HTS) technology. Results: In terms of the GI, the differences between the control and treated groups at 0, 2, and 4 weeks were not statistically significant (all p > 0.05). However, the GI value in the treated group at 6 weeks was significantly lower than that in the control group (p = 0.005). As for the PD, the differences between the control and treated groups at 0, 2, 4, and 6 weeks were not statistically significant (all p > 0.05). Regarding the mSBI, the difference between the control and treated groups at 0 week was not statistically significant (all p > 0.05), while the mSBI value in the treated group at 2, 4, and 6 weeks was significantly lower than that in the control group (p = 0.008, p = 0.005, p = 0.001). Compared to the non-treated group, the hydrogen-rich water-treated group showed a significantly lower number of inflammatory cells, lower pro-inflammatory cytokines, IL-1, IL-6, and MMP-8 levels (p < 0.05). Additionally, there was a significantly decreased relative abundance of pathogenic bacterial species including Porphyromonas gingivalis, Fusobacterium nucleatum, Fusibacter, and Fretibacterium (p < 0.05). Conclusions: The use of hydrogen-rich water for treating peri-implantitis showed promise and effectiveness within the scope of this study.
... Helium gas is known to have a low density and molecular weight (MW). However, molecular hydrogen, which has a lower molecular weight, has been suggested to be a potential therapy for preventive and therapeutic applications against many diseases because in addition to its rapid diffusion, it has protective antioxidant, anti-inflammatory, anti-apoptotic effects [23,24]. Studies have shown that molecular hydrogen, as the lightest and smallest gas molecule, has a unique function as an antioxidant to improve lung function [7,24,25]. ...
... However, molecular hydrogen, which has a lower molecular weight, has been suggested to be a potential therapy for preventive and therapeutic applications against many diseases because in addition to its rapid diffusion, it has protective antioxidant, anti-inflammatory, anti-apoptotic effects [23,24]. Studies have shown that molecular hydrogen, as the lightest and smallest gas molecule, has a unique function as an antioxidant to improve lung function [7,24,25]. Therefore, it has been proposed that the inhalation of a hydrogen/oxygen mixture may be an alternative therapy for COPD [7,15]. The efficacy of hydrogen/oxygen therapy in patients with tracheal stenosis has already been demonstrated [26]. ...
Background:
Recently, chronic lung diseases have been found to be associated with marked inflammation and oxidative stress, which leads to fibrosis in the lungs and chronic respiratory failure. This study aims to determine if hydrogen-rich water (HRW) can enhance oxygen saturation among patients with chronic lung diseases.
Methods:
Ten patients with chronic lung diseases due to COPD (n = 7), bronchial asthma (n = 2), and tuberculosis of the lung (n = 1) with oxygen saturation of 90-95% were provided high-concentration (>5 mM) HRW using H2-producing tablets for 4 weeks. Oxygen saturation was measured via oximeter and blood pressure via digital automatic BP recorder.
Results:
HRW administration was associated with a significant increase in oxygen saturation (SpO2) and decrease in TBARS, MDA, and diene conjugates, with an increase in vitamin E and nitrite levels, compared to baseline levels. Physical training carried out after HRW therapy appeared to increase exercise tolerance and decrease hypoxia, as well as delay the need for oxygen therapy.
Conclusion:
Treatment with HRW in patients with hypoxia from chronic lung diseases may decrease oxidative stress and improve oxygen saturation in some patients. HRW therapy may also provide increased exercise tolerance in patients with chronic hypoxia, but further research is needed.
... [2] The therapeutic medical gas hydrogen, as a drug gas molecule, has the potential to be a new adjunctive treatment for AD. [3,4] In recent years, hydrogen molecules have been found to have a wide range of antioxidant, anti-inflammatory, anti-apoptotic, and rapid diffusion effects, selectively reducing reactive oxygen species and being an antioxidant with neuroprotective properties. [5,6] Hydrogen was found to improve memory loss in AD model mice and to have a therapeutic effect on cognitive dysfunction. ...
... [24,25] Hydrogen as a drug gas molecule is therefore an ideal adjunct to oxygen inhalation, and inhalation of a hydrogen-oxygen mixture is a new adjunctive treatment for AD with a good safety profile. [3,4] Our study showed that the improvement of MMSE score, MoCA score and ADAS-Cog score of the patients in the observation group after treatment was better than that in the control group, indicating that donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of patients with AD can better improve the cognitive function of the patients. Meanwhile, the improvement of ADL score of patients in the observation group was better than that in the control group after treatment, indicating that donepezil combined with hydrogen-oxygen mixture inhalation can better improve the ability of daily living of patients with AD. ...
To investigate the clinical effect of donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of patients with Alzheimer disease (AD), a total of 273 AD patients admitted to our hospital from March 2018 to March 2022 were retrospectively analyzed and assigned into an observation group (n = 138) and a control group (n = 135) according to the different treatment that they received. The control group was treated with donepezil tablets, while the observation group was treated with donepezil tablets combined with hydrogen-oxygen mixture inhalation. The scores of mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer's Disease Assessment Scale-Cognition, activity of daily living scale (ADL) and the P300 event-related potential were compared between the 2 groups. After treatment, MMSE score, MoCA score, and ADL score in both groups increased after treatment (P < .01), while the improvement in the observation group was more significant than that in the control group (P < .001 for MMSE, P = .003 for MoCA, and P = .013 for ADL). The scores of Alzheimer's Disease Assessment Scale-Cognition in the observation group decreased after treatment (P < .05), while the improvement in the observation group was more significant than that in the control group (P = .005). After treatment, the latency of P300 in both groups was shortened (P < .01), and the improvement in the observation group was more significant than that in the control group (P < .001). The amplitude of the observation group increased after treatment (P < .01), and the improvement of the observation group was significant than that of the control group (P = .007). The clinical efficacy of donepezil combined with hydrogen-oxygen mixture inhalation in the treatment of AD is better than that of donepezil alone, which is worthy of further study.
... Research on hydrogen therapy for diseases has been extensive in recent years, [26][27][28][29] and the most prominent and clear mechanism of its therapeutic effect is the antioxidative effect. Hydrogen can selectively neutralize highly toxic free radicals, [30][31][32] such as hydroxyl radicals (-OH) and peroxynitrite anions (ONOO-), while having no neutralizing effect on free radicals with physiological activity. ...
... The mechanisms of inflammation that cause damage to the body include promoting excessive activation of the immune system and the release of inflammatory factors. Multiple studies in recent years have found that molecular hydrogen can reduce the production of inflammatory factors 28,38,39 and increase the release of anti-inflammatory factors, thereby playing an anti-inflammatory role. Hydrogen gas also has anti-apoptotic effects 32,40,41 and affects the hormone levels and activity. ...
Chronic nasal mucosal inflammatory disease is a common nasal disease, which is involved by inflammatory cells and a variety of cytokines. Its main pathological features are inflammatory reaction, increased secretion, mucosal swelling and thickening of nasal cavity or paranasal sinuses.It mainly includes chronic rhinitis (divided into allergic rhinitis, non-allergic rhinitis), chronic sinusitis (divided into with nasal polyps, without nasal polyps type), etc.The main symptoms of chronic rhinitis are nasal itching, sneezing, runny nose, and nasal congestion. The main symptoms of chronic sinusitis are nasal congestion, purulent or sticky nasal discharge, headache, and reduced sense of smell. They are a type of disease with a high incidence rate and seriously affect the quality of human life.Although the etiology and treatment of this type of disease have been extensively studied, there are still many aspects that are unclear.Currently, oxidative stress is believed to be an important link in the pathogenesis of chronic inflammatory diseases of the nasal mucosa. Therefore, anti-oxidative stress is a direction of research for the treatment of chronic nasal mucosal inflammatory diseases.Hydrogen, as a medically therapeutic gas, has been extensively studied for its antioxidant, anti-inflammatory, and anti-damage properties, and has been used in the treatment of various diseases.Although there are relatively few studies on the use of hydrogen for nasal inflammation, its positive effects have also been found. This article systematically summarizes the relevant research on the use of hydrogen to improve chronic nasal mucosal inflammation, with the aim of clarifying the ideas and indicating the direction for further research in the future.
... Its molecular form, hydrogen gas (H 2 ), is colorless, odorless, rare in Earth's atmosphere, and is gaining recognition as a novel energy source [14]. Evidently, H 2 is a potent antioxidative and anti-inflammatory agent with promising potential for medical applications [15,16]. However, because H 2 is flammable, explosive, and dangerous, the much safer hydrogen-rich water (HRW) is often used to replace hydrogen. ...
... In humans, the consumption of HRW by adults effectively alleviated the symptoms of diabetes [18], mitigated cisplatin-induced nephrotoxicity [19], and prevented the risk occurrence of chronic allograft nephropathy after undergoing renal transplantation [20]. The evidence accumulated by these studies suggests that H 2 could protect various cells, tissues, and organs against oxidative injury [15,21,22]. In plants, experiments have shown that H 2 could promote growth vigor and seed germination in certain crops (soybean, barley, canola, spring wheat and mung bean) [23,24], promote the synthesis of anthocyanin in radish sprouts [25], and delay the post-harvest ripening and senescence of kiwifruit [26]. ...
Bispyribac-sodium (BS) is an herbicide often used to control weeds in rice fields. Hydrogen-rich water (HRW) has recently been recommended for alleviating adverse effects, but whether and how HRW alleviates the injury to rice from exposure to BS is still largely unknown. In this study, a greenhouse hydroponic experiment showed that BS alone could substantially inhibit the plant height and fresh weight of both indica and japonica rice seedlings. For indica rice, its pretreatment with HRW at 75% saturation could markedly alleviate the impact on its size but not so with either 50% or 100% HRW. For japonica rice, all the concentrations of HRW used in this study (50%, 75%, and 100% HRW) were capable of reversing the plant size reductions. Further results revealed that the HRW supplement could increase the activity of antioxidative enzymes, including that of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), which assist in the effective removal of ROS (reactive oxygen species). Subsequent results demonstrated a weaker inhibition of the acetolactate synthase (ALS) enzyme within five days by BS in rice seedlings pretreated with HRW than those receiving the BS treatment alone, and that the HRW pretreatment can hasten the rate at which BS is degraded in rice. Taken together, these findings strongly suggest that pretreatment with HRW may offer a promising and effective strategy to improve the ability of rice to tolerate BS.
... So, in vitro cytotoxicity of Mg in our study was primarily due to ROS and alkaline pH. However, in vitro and in vivo cytotoxicity is different, where hydrogen gas has more significance in vivo, as quick and large accumulations of hydrogen gas pockets have been found to cause tissue necrosis if not adequately punctured [94,95], and hydrogen gas when produced at a proper rate is an antioxidant and scavenge ROS [96]. Therefore, for future studies, it will be interesting to study more closely how the ROS and hydrogen gas produced from the Mg surface during degradation simultaneously affect the microenvironment and cells temporally and spatially. ...
Magnesium (Mg) alloys are popular biodegradable metals studied for orthopedic and cardiovascular applications, mainly because Mg ions are essential trace elements known to promote angiogenesis and osteogenesis. However, Mg corrosion consists of oxidation and reduction reactions that produce by-products, such as hydrogen gas, reactive oxygen species, and hydroxides. It is still unclear how all these by-products and Mg ions concomitantly alter the microenvironment and cell behaviors spatially and temporally. This study shows that Mg corrosion can enhance cell proliferation by reducing intracellular ROS. However, Mg cannot decrease ROS and promote cell proliferation in simulated inflammatory conditions, meaning the microenvironment is critical. Furthermore, cells may respond to Mg ions differently in chronic or acute alkaline pH or oxidative stress. Depending on the corrosion rate, Mg modulates HIF1α and many signaling pathways like PI3K/AKT/mTOR, mitophagy, cell cycle, and oxidative phosphorylation. Therefore, this study provides a fundamental insight into the importance of reduction reactions in Mg alloys.
... Molecular hydrogen, as an emerging medical gas with comprehensive effects of rapid diffuse, anti-apoptotic, antiinflammatory, and antioxidant, has shown favorable effects to various diseases (6,7). Numerous studies have reported that the application of hydrogen is therapeutic for neurodegeneration (8,9), cerebral infarction (10,11), chronic obstructive pulmonary disease (12, 13), metabolic syndrome (14, 15), non-alcoholic fatty liver disease (16, 17), cancer (18,19). ...
Aim
To evaluate the real-life effectiveness and safety of hydrogen inhalation (HI) therapy as an additional treatment in Chinese adults with hypertension.
Methods
This observational, retrospective clinical study included hypertensive patients receiving routine antihypertensives with or without HI initiation from 2018 to 2023. Participants were assigned to the HI group or non-HI group (control group) after propensity score matching. The changes in mean systolic blood pressure (SBP) level during the 24-week follow-up period in different groups were examined primarily. The secondary outcome was the changes in diastolic blood pressure (DBP) and blood pressure (BP) control rate during the study. Several subgroup and sensitivity analyses were performed to confirm the robustness of our main findings. Adverse event (AE) was also assessed in patients of both groups.
Results
In total, we selected 2,364 patients into the analysis. Both mean SBP and DBP levels significantly decreased in the HI group compared to control group at each follow-up visit with the between group difference of −4.63 mm Hg (95% CI, −6.51 to −2.74) at week 8, −6.69 mm Hg (95% CI, −8.54 to −4.85) at week 16, −7.81 mm Hg (95% CI, −9.57 to −6.04) at week 24 for SBP, and −1.83 mm Hg (95% CI, −3.21 to −0.45) at week 8, −2.57 mm Hg (95% CI, −3.97 to −1.17) at week 16, −2.89 mm Hg (95% CI, −4.24 to −1.54) at week 24 for DBP. Patients in the HI group were more likely to attain controlled BP at the follow-up period with odds ratio of 1.44 (95% CI, 1.21–1.72) at week 8, 1.90 (95% CI, 1.59–2.27) at week 16, and 2.24 (95% CI, 1.87–2.68) at the end. The trends of subgroup and sensitivity analyses were mostly consistent with the main analysis. The incidences of AEs were similar between the HI group and control group with all p-value >0.05.
Conclusion
The HI therapy is related to significant amelioration in BP levels with acceptable safety profile in Chinese hypertensive adults after 24 weeks of treatment, building a clinical ground for further research to evaluate the antihypertensive effect of HI therapy.
... Although the pH on pure Mg surfaces is typically >10 in neutral solutions, physiological buffering reduces it, with pH values around Mg screws ranging from 7. 8-8.9. H 2 gas: H 2 is a unique degradation product that is non-toxic at high concentrations [71] and plays a role in reducing oxidative stress and inflammation [72,73]. It selectively decreases harmful oxidative radicals without disrupting normal cellular oxidative processes [74,75]. ...
Magnesium (Mg)-based alloys have garnered significant attention for orthopedic implants due
to their exceptional combination of biodegradability, biocompatibility, and mechanical
properties that closely resemble natural bone. This review addresses the corrosion aspects of
Mg-based alloys, emphasizing the dual nature of corrosion products, which can positively
influence osteogenesis and potentially hinder tissue integration. The favorable biological
effects of Mg alloys, including their support for bone growth are thoroughly examined,
showcasing their potential to enhance bone healing and regeneration. Additionally, the review
delves into the various biocompatible alloying elements used to improve the mechanical
properties and corrosion resistance of various Mg alloy systems. The interactions between these
alloying elements and the Mg matrix are discussed in detail to provide insights into their
contributions to mechanical strength and longevity. Ultimately, this review offers a
comprehensive overview of the advancements in developing Mg-based alloys for orthopedic
implants. By examining the intricate interplay between alloy composition, corrosion behavior,
mechanical properties, and biological effects, the review aims to guide future research and
development efforts. Alloying with elements such as zinc, calcium, and strontium demonstrates
the potential for enhancing corrosion resistance and mechanical strength. However, challenges
like the rapid corrosion of Magnesium and the evolution of hydrogen gas persist. Future
research should prioritize the optimization of alloy compositions, surface modifications, and
long-term biocompatibility studies to improve clinical applicability. Magnesium alloys have
considerable potential to serve as alternatives to conventional implants, potentially decreasing
the need for secondary surgeries and enhancing patient outcomes. The goal is to optimize Mg
alloys for successful clinical applications, ensuring they meet the stringent requirements of
orthopedic implant materials while maximizing patient outcomes.
Keywords: Magnesium, Alloy, Mechanical, Corrosion, Orthopedic implant
... Over the past few years, molecular hydrogen (H 2 ) has gradually gained interest as a potential new treatment option [20,21], and the anti-inflammatory and antioxidant properties of H 2 in a range of diseases have been demonstrated in several studies [22][23][24]. H 2 has been described as an antioxidant that suppresses the amounts of peroxynitrite (ONOO − ) and hydroxyl radicals ( • OH) to protect cells from OS [25]. Moreover, H 2 has been shown to exert anti-inflammatory effects, notably through its ability to downregulate pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α [25]. ...
Airway inflammatory diseases, such as asthma, are a global public health concern owing to their chronic inflammatory effects on the respiratory mucosa. Molecular hydrogen (H2) has recently been recognized for its antioxidant and anti-inflammatory properties. In this study, we examined the therapeutic potential of H2 in airway inflammation using an ovalbumin (OVA)-induced BALB/c mouse model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA to induce airway inflammation, and 30 mice were randomly divided into five groups: NT (non-treatment), HTC (3% H2 treatment only), NC (negative control, OVA only), PC (positive control, OVA + intranasal 1 mg/mL salbutamol 50 μL), and HT (H2 treatment, OVA + inhaled 3% H2). Various inflammatory and oxidative stress (OS)-induced markers such as white blood cells (WBCs) and their differential counts, lung histology, cytokine levels such as interleukin (IL)-4, (IL)-5, (IL)-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), (IL)-10, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT), and total immunoglobulin E (IgE) levels were investigated. Our results showed that inhaled H2 significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity. Furthermore, H2 also significantly decreased serum IgE levels, a marker of allergic inflammation. Collectively, our findings suggest that H2 inhalation is a promising treatment option for airway inflammation, offering a novel approach with potential clinical applications.
... Hydrogen has shown anti-inflammatory effects in various animal models, such as reducing the levels of inflammatory mediators such as TNF-α, IL-6, IL-1, IL-4, and IL-13. 15,[33][34][35] Hydrogen can improve nasal mucosal inflammation by increasing the number and function of Treg cells, increasing the release of anti-inflammatory factors (TGF-β and IL-10), 9,13 or by inhibiting the secretion of inflammatory factors (IL-4, IL-13, etc) by Th2 cells. 9,15 CRS is a chronic inflammation of nasal mucosa, surgery only removes obstructive lesions, and further drug therapy is needed to reverse the chronic inflammation of nasal mucosa. ...
Purpose
The treatment of chronic rhinosinusitis (CRS) is often a difficult and long-term behavior, so it is necessary to seek a local treatment method that can be used for a long time, and is safe and effective. Nasal saline irrigation after functional endoscopic sinus surgery (FESS) is currently recognized as a local treatment method, but it has no anti-inflammatory, anti-damage, and healing-promoting functions. To investigate the efficacy and safety of hydrogen-rich saline (HRS) for nasal irrigation after CRS surgery.
Patients and Methods
A total of 61 patients after CRS completed the study. Subjects were randomly assigned to rinse the nasal cavity with HRS or normal saline (NS) after CRS. Participants were followed up once a week for 12 times, and were evaluated with visual analogue score (VAS), 22-item Sinonasal Outcomes Test (SNOT-22), and Lund-Kennedy endoscopy scores (LKES). The primary outcome was the VAS score of patients.
Results
After 12 weeks of follow-up, the VAS scores of both groups decreased, and the HRS group (0.52±0.85) was lower than the NS group (1.47±1.55), P=0.005. The total number of cases with complete control (clinical cure) in the short-term efficacy evaluation was more in the HRS group (20/31) than in the NS group (11/30), P=0.03<0.05. No obvious adverse reactions occurred in the two groups during the follow-up.
Conclusion
This study found that HRS was more effective than NS alone in nasal irrigation after CRS surgery, and could shorten the time of nasal mucosal healing and epithelialization, with a higher rate of recent complete control.
... Recent studies have shown that H 2 can activate endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and reduce the concentrations of various oxidative stress markers such as myeloperoxidase (MPO), malondialdehyde (MDA), 8-isoprostaglandin F2 and thiobarbituric acid with a dose-dependent pattern in many human diseases and rodent models. [52][53][54][55] ...
Hydrogen (H2) therapy is an emerging, novel, and safe therapeutic modality that uses molecular hydrogen for effective treatment. However, the impact of H2 therapy is limited because hydrogen molecules predominantly depend on the systemic administration of H2 gas, which cannot accumulate at the lesion site with high concentration, thus leading to limited targeting and utilization. Biomaterials are developed to specifically deliver H2 and control its release. In this review, the development process, stimuli‐responsive release strategies, and potential therapeutic mechanisms of biomaterial‐based H2 therapy are summarized. H2 therapy. Specifically, the produced H2 from biomaterials not only can scavenge free radicals, such as reactive oxygen species (ROS) and lipid peroxidation (LPO), but also can inhibit the danger factors of initiating diseases, including pro‐inflammatory cytokines, adenosine triphosphate (ATP), and heat shock protein (HSP). In addition, the released H2 can further act as signal molecules to regulate key pathways for disease treatment. The current opportunities and challenges of H2‐based therapy are discussed, and the future research directions of biomaterial‐based H2 therapy for clinical applications are emphasized.
... Molecular hydrogen (H 2 ) is a diatomic gas that is colorless, tasteless, odorless, non-irritating, and highly flammable. It has been found to have positive effects on multiple organ systems, including the brain, heart, lung, kidney, liver, and pancreas [6][7][8]. H 2 has shown protective effects against oxidative stress by mitigating inflammatory responses in diseases such as Alzheimer's disease, hematological disorders and chronic obstructive pulmonary disease (COPD) [9,10]. Studies have reported that inhaling H 2 can dose-dependently alleviate lung inflammation induced by cigarette smoke in rats [10]. ...
Background
As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats.
Methods
PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg− 1·wk− 1 for 2 weeks. Inhalation of hydrogen gas (H2) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined.
Results
Inhaled H2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H2 preserved p-Smad3 and induced p-Smad1/5/9.
Conclusion
Inhalation of H2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H2.
... The use of medical gases for oxidative stress therapy seems to be particularly promising. Medical gases can be administered to patients by inhalation using several devices such as nasal cannula, a ventilator circuit, or a face mask [56][57][58]. ...
Acute limb ischemia (ALI) is defined as a sudden reduction in blood flow to a limb, resulting in cessation of blood flow and, therefore, cessation of the delivery of nutrients and oxygen to the tissues of the lower limb. Despite optimal treatment to restore blood flow to ischemic tissues, some patients may suffer from ischemia/reperfusion (I/R) syndrome, the most severe complication after a revascularization procedure used to restore blood flow. There are multiple molecular and cellular factors that are involved in each phase of ALI. This review focuses firstly on molecular and cellular factors of arterial thrombosis, highlighting the role of atherosclerotic plaques, smooth muscle cells (SMCs), and cytokine which may alter key components of the extracellular matrix (ECM). Then, molecular and cellular factors of arterial embolism will be discussed, highlighting the importance of thrombi composition. Molecular and cellular factors of ischemia/reperfusion syndrome are analyzed in depth, highlighting several important mechanisms related to tissue damage, such as inflammation, apoptosis, autophagy, necrosis, and necroptosis. Furthermore, local and general complications of ALI are discussed in the context of molecular alterations. Ultimately, the role of novel biomarkers and targeted therapies is discussed.
... Ingestion of hydrogen water typically aims to provide ~0.5-1 mM hydrogen concentration in blood. Higher hydrogen inhalation doses around 2-4% by volume have been used as well [ 44 ]. ...
Chronic, non-healing wounds represent a major clinical challenge with substantial economic burden. Impaired wound healing stems from excessive inflammation, infection, ischemia, and oxidative stress. Molecular hydrogen has recently emerged as a therapeutic medical gas with antioxidant, anti-inflammatory, and cytoprotective properties through selective free radical scavenging, activating antioxidant enzymes, reducing pro-inflammatory cytokines, and potentially modulating cell signaling. Arly preclinical evidence shows hydrogen therapy may promote wound healing through accelerated closure, decreased inflammation, and mitigated tissue injury. Initial small-scale human pilots and case reports demonstrate feasibility and apparent safety of administering hydrogen via inhalation, ingestion, topical application, or baths. However, rigorous clinical trials validating therapeutic efficacy are lacking. Further research should optimize delivery, dose, timing, and tissue bioavailability to translate promising preclinical findings into effective clinical hydrogen treatments for wound care. Definitive large-scale studies are critical next steps.
... Molecular hydrogen (H 2 ), a small molecule with the capacity to efficiently enter the plasma membrane and other cell organelles, exerts multiple biological effects involving antioxidation, anti-inflammation, anti-apoptosis, and anti-fibrosis in many diseases of different systems [13]. Previous studies have demonstrated that H 2 can protect cisplatin-induced, ferric nitrilotriacetate-induced, cyclosporine A-induced, sepsisinduced, oxalate-induced and glycerol-induced renal injury [14][15][16][17][18][19]. ...
Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1β) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.
... Introduction species (ROS) or reactive nitrogen species (RNS), which are involved in normal cell signaling. [8][9][10][11][12][13] This selective targeting makes hydrogen a safe and effective therapeutic option. Clinical experiments demonstrated the safety of hydrogen gas and showed its benefits in different medical fields, [14][15][16] including sports medicine, 17,18 cognitive impairment, 19 stroke, 20 cancer, 21 metabolic syndrome, 22 and in patients with COVID-19. ...
The redox balance in the intestine plays an important role in maintaining intestinal homeostasis, and it is closely related to the intestinal mucosal barrier, intestinal inflammation, and the gut microbiota. Current research on the treatment of ulcerative colitis has focused on immune disorders, excessive inflammation, and oxidative stress. However, an imbalance in intestinal redox reaction plays a particularly critical role. Hydrogen is produced by some anaerobic bacteria via hydrogenases in the intestine. Increasing evidence suggests that hydrogen, as an inert gas, is crucial for immunity, inflammation, and oxidative stress and plays a protective role in ulcerative colitis. Hydrogen maintains the redox state balance in the intestine in ulcerative colitis and reduces damage to intestinal epithelial cells by exerting its selective antioxidant ability. Hydrogen also regulates the intestinal flora, reduces the harmful effects of bacteria on the intestinal epithelial barrier, promotes the restoration of normal anaerobic bacteria in the intestines, and ultimately improves the integrity of the intestinal epithelial barrier. The present review focuses on the therapeutic mechanisms of hydrogen-targeting ulcerative colitis.
... Novým příslibem do budoucna v oblasti zmírňování příznaků DOMS by mohla být také aplikace molekulárního vodíku (H2). Soubor unikátních biologických účinků H2, především selektivně antioxidačních, anti-apopotických a protizánětlivých (Huang et al., 2010;Ohsawa et al., 2007;Ohta, 2014), by mohl významně ovlivnit podstatnou část příčin vzniku DOMS po tělesné práci. I přes tuto skutečnost se z dostupné literatury jeví, že této problematice zefektivnění regeneračních procesů po tělesném zatížení s využitím H2 nebyla prozatím věnována dostatečná pozornost. ...
Východiska Jednorázová vytrvalostní pohybová aktivita u netrénovaných osob je spojována s výskytem opožděné svalové bolesti související s probíhajícím lokální zánětem a zvýšeným oxidativním stresem. Molekulární vodík (H2) je nový selektivně působící antioxidant a protizánětlivě působící látka. Cíl Hlavním cílem studie bylo posoudit vliv aplikace H2 obohacené vody (HRW) na rozvoj pozátěžové svalové bolesti během 24 hod od ukončení 5 km běhu. Metodika V rámci randomizované studie podstoupilo 12 vytrvalostně netrénovaných mužů ve věku 23,6 ± 3,4 roku běh na 5 km s cílem dosažení nejlepšího běžeckého výkonu. V průběhu dvou dnů před zatížením a do 60 min po ukončení byla probandům aplikována celková dávka 3780 ml HRW nebo placeba. V časech 0 h, 1 h, 4 h a 24 h po zátěži byla hodnocena bolestivost dolních končetin pomocí 100 mm vizuální analogové škály. Odstup mezi oběma měřeními činil 7 dnů. Výsledky Aplikace HRW v porovnání s placebem signifikantně redukuje pozátěžovou bolest dolních končetin během 1. h (41 ± 21 vs. 27 ± 13 mm; p=0,017) a 4. h (34 ± 21 vs. 22 ± 15 mm; p=0,029). Rozdíly po 24 h se blížily statistické významnosti (36 ± 27 vs. 26 ± 16 mm; p = 0,081). Závěr Konzumace HRW významně snižuje pozátěžovou percepci svalové bolesti s tendencí zmírňovat i opožděnou svalovou bolest po absolvování 5km běhu u netrénované populace.
... It can also be applied transdermally by applying H 2 saturated water or mixing chemicals together that react to form H 2 [2,3]. All these approaches achieve a transient increase in the concentration of H 2 , along with beneficial effects on cell function [4][5][6][7][8]. Although administration of H 2 by inhalation or ingestion is the predominant method, application of H 2 transdermally provides targeted delivery to specific tissue, allowing for a local effect with a powerful H 2 concentration gradient. ...
Molecular hydrogen (H2) emerged a decade ago as a potent therapeutic and is attracting more and more attention. The beneficial effects of H2
... Molecular hydrogen, as an inert gas with ability of antioxidant, anti-inflammatory, anti-apoptotic and rapid diffuses, has been widely considered as an effective strategy for various diseases in the past few years. 11,12 Recently, hydrogen has shown nonnegligible therapeutic effects in diabetes mellitus. It is reported that the supplement of hydrogen molecule significantly reduces FPG and improve insulin sensitivity in diabetic animal models. ...
Aim
To evaluate the real-life effectiveness and safety of Chinese patients with type 2 diabetes mellitus (T2DM) receiving hydrogen inhalation (HI) treatment as a supplementary treatment.
Methods
This retrospective, multicenter, observational 6-months clinical study included T2DM patients maintaining HI, visited at 4 time points. The primary outcome is the mean change in glycated hemoglobin (HbA1c) at the end of the study compared to baseline. The secondary outcome is analyzing the mean change of fasting plasma glucose (FPG), weight, lipid profile, insulin dose and homeostasis model assessment. Linear regression and logistics regression are applied to evaluate the effect of HI after the treatment.
Results
Of the 431 patients comprised, it is observed a significant decrease in HbA1c level (9.04±0.82% at baseline to 8.30±0.99% and 8.00±0.80% at the end, p<0.001), FPG (165.6±40.2 mg/dL at baseline to 157.1±36.3mg/dL and 143.6±32.3mg/dL at the end, p<0.001), weight (74.7±7.1kg at baseline to 74.8±10.0kg and 73.6±8.1kg at the end, p<0.001), insulin dose (49.3±10.8U/d at baseline to 46.7±8.0U/d and 45.2±8.7U/d, p<0.001). The individuals in subgroup with higher baseline HbA1c and longer daily HI time duration gain greater HbA1c decrease after 6 months. Linear regression shows that higher baseline HbA1c level and shorter diabetes duration are significantly in relation to greater HbA1c reduction. Logistics regression reveals that lower weight is associated with a higher possibility of reaching HbA1c<7%. The most common adverse event is hypoglycemia.
Conclusion
HI therapy significantly improves glycemic control, weight, insulin dose, lipid metabolism, β-cell function and insulin resistance of patients with type 2 diabetes after 6 months. Higher baseline HbA1c level and shorter diabetes duration is related to greater clinical response to HI.
... In 2007, Professor Shigeo Ohta discovered that hydrogen (H 2 ) can selectively scavenge hydroxyl radical (-OH) and nitrite anion free radical (ONOO-) to alleviate oxidative damage caused by middle cerebral artery ischemia/reperfusion (I/R) in rats. 1 Since then, H 2 has emerged as a promising area of research in medical gas therapy. 2 As the simplest and colorless small molecule gas, H 2 has been studied for over a decade and has shown various physiological regulatory activities and signal transduction functions. In the field of medicine, animal model studies and clinical trials have shown that H 2 has antiinflammatory, anti-apoptotic, and anti-oxidative effects, but the main molecular targets have yet to be identified. ...
Hydrogen is a simple, colorless, and biologically active small molecule gas that can react with reactive oxygen species. Recent research suggests that hydrogen possesses several biological effects, including antioxidant, anti-inflammatory, and anti-apoptotic effects, while exhibiting an extremely high level of safety. Hydrogen application has shown promise in treating a range of acute and chronic diseases, both benign and malignant. Importantly, an increasing number of clinical studies on hydrogen have demonstrated its efficacy and safety in treating various diseases. This review highlights the beneficial effects of hydrogen in kidney diseases, summarizes potential mechanisms by which hydrogen may act in these diseases, and proposes several promising avenues for future research.
... Within the scope of PD, it is known that the levels of reactive oxygen species are strictly controlled by various antioxidant mechanisms in healthy dopaminergic neurons (Puspita et al., 2017;Amri et al., 2017). This group of neurons is susceptible to oxidative stress since numerous oxidants are produced in enzymatic and non-enzymatic reactions that DA suffers when released into the synaptic cleft or cytosol (Huang et al., 2010). ...
L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia is a side effect of Parkinson's disease treatment and it is characterized by atypical involuntary movements. A link between neuroinflammation and L-DOPA-induced dyskinesia has been documented. Hydrogen gas (H2) has neuroprotective effects in Parkinson's disease models and has a major anti-inflammatory effect. Our objective is to test the hypothesis that H2 inhalation reduces L-DOPA-induced dyskinesia. 15 days after 6-hydroxydopamine lesions of dopaminergic neurons were made (microinjection into the medial forebrain bundle), chronic L-DOPA treatment (15 days) was performed. Rats were exposed to H2 (2% gas mixture, 1 h) or air (controls) before L-DOPA injection. Abnormal involuntary movements and locomotor activity were conducted. Striatal microglia and astrocyte was analyzed and striatal and plasma samples for cytokines evaluation were collected after the abnormal involuntary movements analysis. H2 inhalation attenuated L-DOPA-induced dyskinesia. The gas therapy did not impair the improvement of locomotor activity achieved by L-DOPA treatment. H2 inhalation reduced activated microglia in the lesioned striatum, which is consistent with the observed reduced pro-inflammatory cytokines levels. Display of abnormal involuntary movements was positively correlated with plasma IL-1β and striatal TNF-α levels and negatively correlated with striatal IL-10 levels. Prophylactic H2 inhalation decreases abnormal involuntary movements in a preclinical L-DOPA-induced dyskinesia model. The H2 antidyskinetic effect was associated with decreased striatal and peripheral inflammation. This finding has a translational importance to L-DOPA-treated parkinsonian patients' well-being.
... Indeed, numerous literature have shown that hydrogen gas treatment ameliorated IR injury in experimental models, including cardiac ischemia, intestinal or lung transplantation, as well as hemorrhagic shock. 5,6 Although the precise mechanisms are not fully understood, hydrogen gas exhibits anti-oxidative effects partly through eliminating ROS. In addition, hydrogen gas exerts antiinflammatory and anti-apoptotic effects under various physiological and pathological conditions. ...
Objectives
Crush syndrome (CS) is characterized by a systemic manifestation of traumatic rhabdomyolysis, leading to multiple organ dysfunction and death. Ischemia-reperfusion (IR) injury is commonly responsible for systemic response. Extending studies have shown that hydrogen gas treatment ameliorated IR injury in numerous experimental models; however, its effect on CS has not been well examined. This study aimed to investigate the effects of hydrogen gas inhalation following crush injury in an experimental model of CS.
Methods
Male Sprague-Dawley rats were subjected to experimental CS by applying a total of 3.0 kg weight to both hindlimb under general anesthesia for 6 h. Immediately after decompression, the animals were randomly placed in a gas chamber filled with either air or 1.3% hydrogen gas. Animals were sacrificed 18 h or 24 h following gas exposure for non-survival studies or for survival study, respectively.
Results
The rats with hydrogen treatment ( n = 6) had a higher 24-h survival than the rats with air treatment ( n = 9) (100% vs. 44%, p = 0.035). Lactate concentrations (2.9 ± 0.2 vs. 2.2 ± 0.2 mmol/L, p = 0.040) and creatine kinase (34,178 ± 13,580 vs. 5005 ± 842 IU/L, p = 0.016) were lower in the hydrogen group compared with the air group 18 h after decompression ( n = 4 in the air group, and n = 5 in the H 2 group). Histological analysis revealed that the damage to the rectus femoris muscle and kidney appeared to be ameliorated by hydrogen treatment.
Conclusion
Hydrogen gas inhalation may be a promising therapeutic approach in the treatment of CS.
... Hydrogen in the atomic form is the simplest element, consisting of only one electron and one proton, but it exists primarily in its diatomic form (H 2 ). It is a tasteless, odorless, colorless, and non-toxic nonmetallic gas [10]. Hydrogen is at the center of the prevailing cosmological model that describes the early development of the universe [11] as well as the origin of life itself [12,13]. ...
Over 2000 publications including more than 100 human studies seem to indicate that humans have only recently benefited from or known about the medical effects of H2 within the past 15 years. However, we have unknowingly benefited from H2 since the dawn of time, from H2-producing bacteria to the use of naturally occurring hydrogen-rich waters. Moreover, the first writings on the therapeutic effects of H2 date to around 1793. Since then, papers appeared sporadically in the literature every few decades but never exploded until Ohsawa et al. again demonstrated hydrogen’s therapeutic effects in 2007. This landmark paper appears to have been the spark that ignited the medical interest in hydrogen. Although H2 was used in the 1880s to locate intestinal perforations, in the 1940s in deep sea diving, and in the 1960s to measure blood flow, H2 was largely viewed as biologically inert. This review highlights the history of hydrogen in the genesis/evolution of life and its medicinal and non-medicinal use in humans. Although hydrogen medicine has a long and erratic history, perhaps future history will show that, this time around, these 15 years of ignited interest resulted in a self-sustaining explosion of its unique medical effects.
... Many microalgae and cyanobacteria can express hydrogenases that reduce protons to gaseous H 2 (11). Since the antioxidant property of H 2 in animals was observed by Ohsawa et al. (12), H 2 is gradually regarded as a therapeutic medical gas (13). In plants, H 2 has been found to act as one of the beneficial gasotransmitters in responses to various abiotic stresses (14), including cadmium exposure in alfalfa (15) and cucumber (16), and salinity in Arabidopsis (17). ...
Although molecular hydrogen has potential therapeutic effects in animals, whether or how this gas functions in plant disease resistance has not yet been elucidated. RSV was considered the most devastating plant virus in rice, since it could cause severe losses in field production.
... As a therapeutic medical gas, hydrogen (H 2 ) has several properties such as antioxidants, reducing inflammation in cell tissues, and inert. [1][2] H 2 is aided to the body via various routes such as inhalation of hydrogen-containing air (HCA), oral ingestion using hydrogen-rich water (HRW), and H 2 saline injection. ...
As a therapeutic medical gas, hydrogen (H2) has several properties such as antioxidants,
reducing inflammation in cell tissues, and inert.[1-2] H2 is aided to the body via various
routes such as inhalation of hydrogen-containing air (HCA), oral ingestion using
hydrogen-rich water (HRW), and H2 saline injection.
Recently many products for HCA and HRW therapy have been manufactured
and marketed. However, this product has never been checked regarding its safety,
especially regarding the impurities in the gas. Furthermore, the H2 production from the
electrolysis process has been known to be accompanied by side product gas such as
hydrocarbons and CO. Therefore, we have investigated the impurities content in the HCA
and HRW therapy products using gas chromatography (GC) instrument. First, gas
reference standards (GRS) measurements were used to calibrate the instrument and
determine the gas separation. For example, for the detection of hydrocarbons, the
instrument setup is as follows: the gas column was alumina; the detector was a flame
ionization detector (FID); the detector temperature was 250 °C, and the oven temperature
was 100 °C. Afterward, the 10 HCA and HRW devices samples were measured using
the setup.
The results show that H2 gas generated from the devices contains impurities
from hydrocarbons (with the maximum value) CH4(5.38 µmol/mol), C2H6 (1.2 µmol/mol),
C2H4 (1.22 µmol/mol), C3H8 (1.17 µmol/mol), C4H10 (2.08 µmol/mol), C2H2 (1.00
µmol/mol), C4H8 (2.85 µmol/mol), and C4H6 (1.14 µmol/mol). A Molseive column then
replaced the gas column to detect CO. Measurement shows the maximum CO impurities
in the samples is 13.2 µmol/mol. These findings reveal that while hydrogen gas has a
positive impact on the body, negative consequences might arise due to the presence of
other gases from the electrolysis process.
... Previous studies have demonstrated that feed supplemented with C. butyricum can boost growth performance, balance intestinal flora, and promote immune responses in broilers (Cassir et al. 2016;Huang et al. 2019;Han et al. 2018). Butyric acid is the most important metabolite of C. butyricum and endows C. butyricum with antioxidant effects on the colonic mucosa (Hamer et al. 2009;Ohsawa et al. 2007;Huang et al. 2010). However, there are only few reports on the effects of C. butyricum on anti-oxidant activity in broilers. ...
Low-protein (LP) feeds are used in the poultry industry to combat the increasing consumption of protein resources and reduce environmental pollution caused by excessive nitrogen excretion. Dietary supplementation of protease or Clostridium butyricum increases the growth performance of broilers; however, it is unclear whether they counteract the negative effects of LP diets. The effects of protease and C. butyricum on growth performance, intestinal morphology, anti-oxidant capacity, anti-inflammatory response, and microbial community of broilers have not been studied extensively. Here, 450 healthy 1-day-old Cobb500 broilers were allocated to five groups, according to different diets: basal diet (Control); LP diet (LP; 2% less crude protein than the control); LP diet + 200 g/t HuPro protease (LPH); LP diet + 1.0 × 10⁹ CFU/t C. butyricum (LPC); and basal diet + 200 g/t oxytetracycline (Antibiotic). Supplementing both C. butyricum and protease improved the growth performance of broilers. The supplementation of HuPro protease under low-protein conditions could achieve a breeding effect similar to that of the positive control (Antibiotic). Supplementing C. butyricum could maintain intestinal barrier function, alleviate the inflammatory response, and increase ileal and cecal short-chain fatty acid concentrations. Both C. butyricum and protease altered the bacterial diversity in the cecum, increased Bacteroidetes abundance, and resulted in higher abundance of Rikenellaceae RC9 gut spp. and lower abundance of Alistipes spp. in broilers. This study demonstrates the positive effects of proteases and C. butyricum on broilers and serves as a reference for the selection of appropriate supplementation for broilers in the poultry industry.
Key points
• Low-protein diet had a negative effect on growth performance of broilers.
• Protease significantly reduced feed conversion rate.
• Clostridium butyricum had positive effects on broilers.
... Recent studies have shown that hydrogen gas (H 2 ) is an important physiological regulatory factor with antioxidant, anti-inflammatory, and anti-apoptotic properties [26]. In the present study, we investigated the protective effects of H 2 treatment in LPS-induced ALI mice. ...
Background
Chronic inflammation and oxidant/antioxidant imbalance are two main pathological features associated with lipopolysaccharide (LPS)-induced acute lung injury (ALI). The following study investigated the protective role of hydrogen (H2), a gaseous molecule without known toxicity, in LPS-induced lung injury in mice and explored its potential molecular mechanisms.
Methods
Mice were randomly divided into three groups: H2 control group, LPS group, and LPS + H2 group. The mice were euthanized at the indicated time points, and the specimens were collected. The 72 h survival rates, cytokines contents, pathological changes, expression of Toll-like receptor 4 (TLR4), and oxidative stress indicators were analyzed. Moreover, under different culture conditions, RAW 264.7 mouse macrophages were used to investigate the potential molecular mechanisms of H2 in vitro. Cells were divided into the following groups: PBS group, LPS group, and LPS + H2 group. The cell viability, intracellular ROS, cytokines, and expression of TLR4 and nuclear factor kappa-B (NF-κB) were observed.
Results
Hydrogen inhalation increased the survival rate to 80%, reduced LPS-induced lung damage, and decreased inflammatory cytokine release in LPS mice. Besides, H2 showed remarked anti-oxidative activity to reduce the MDA and NO contents in the lung. In vitro data further indicated that H2 down-regulates the levels of ROS, NO, TNF-α, IL-6, and IL-1β in LPS-stimulated macrophages and inhibits the expression of TLR4 and the activation of nuclear factor kappa-B (NF-κB).
Conclusion
Hydrogen gas alleviates lipopolysaccharide-induced acute lung injury and inflammatory response most probably through the TLR4-NF-κB pathway.
... Its molecular form, hydrogen gas (H2), is a colorless, odorless and tasteless gas. Since H2 was first purified by Robert Boyle in 1671, it has been known as a reducing gas [1]. The production of H2 was first observed in bacteria [2] and then in green algae [3]. ...
Hydrogen gas (H2) is a unique molecular messenger, which is known to be involved in diverse physiological processes in plants, from seed germination to seedling growth to regulation of environmental stresses. In this review, we focus on the role of H2 in plant responses to abiotic stresses, such as temperature, osmotic stress, light, paraquat (PQ)-induced oxidative stresses, and metal stresses. In general, H2 can alleviate environmental stresses by improving the antioxidant defense system, photosynthetic capacity, re-establishing ion homeostasis and glutathione homeostasis, maintaining nutrient element homeostasis, mediating glucose metabolism and flavonoid pathways, regulating heme oxygenase-1 (HO-1) signaling, and interaction between H2 and nitric oxide (NO), carbonic oxide (CO), or plant hormones. In addition, some genes modulated by H2 under abiotic stresses are also discussed. Detailed evidence of molecular mechanisms for H2-mediated particular pathways under abiotic stress, however, is scarce. Further studies regarding the regulatory roles of H2 in modulating abiotic stresses research should focus on the molecular details of the particular pathways that are activated in plants. More research work will improve knowledge concerning possible applications of hydrogen-rich water (HRW) to respond to abiotic stresses with the aim of enhancing crop quality and economic value.
... Safety In its gaseous state H2 has a flammability range of 4% -94% at standard pressure and temperature. 48 Therefore calculations assessing the inhalation volume of H2 should be conducted before administration. For example, if a patient is experiencing rapid or shallow breathing, or has a chronic lung condition, it would be beneficial to conduct a simple spirometry test to ensure accurate measurement of tidal volume and H2 consumption, using the formula: (mL/sec): H2 / (Breath -H2) x 100 H2 is classified as a 'generally regarded as safe' (GRAS) product by the Food and Drug Administration (U.S.), 49 and is regarded as a food supplement (E949) under part C group I of regulation 1129/2011 in the European Union 50,51 and U.K. 52 ...
Coronavirus Infectious Disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) that emerged as a novel pathogen of global concern in the latter stages of 2019. COVID-19 is a highly contagious disease which can be transmitted through aerosol droplets and surface-to-host contact. Both symptomology and the severity of disease can vary wildly between individuals, from asymptomatic but infectious, to those that require critical care. Due to the neoteric emergence of SARS-CoV-2, current treatment strategies are not yet well developed and rely on the repurposing of such medications as antiviral, corticosteroid, immunosuppressant and oxygen (O2) therapies. However, the minimal efficacy of these interventions is concerning. In addition to the acute infection that prevails, it is estimated that up to 30% of adults who contract COVID-19 develop chronic symptoms lasting longer than 12 weeks. It is also estimated that 15% of children aged 2-16 years have developed long-lasting sequelae associated with SARS-CoV-2 infection. According to recent clinical data, molecular hydrogen (H2) and oxy-hydrogen (H2/O2) therapies successfully remediated the debilitating effects of SARS-CoV-2 infection in adults. By acting as an effective anti-inflammatory and antioxidative agent, it is reported that H2 administration can improve recovery through abatement of the hyperinflammatory cytokine cascade and reduction of inhalation resistance in patients with mild-moderate disease symptoms. In this review, the authors investigate the clinical and empirical evidence relating to treating the symptoms of both acute and chronic COVID-19 with H2-containing therapeutics.
... Molecular hydrogen (H2) is a colorless, tasteless, odorless, flammable gas [1]. H2 is also a minimal molecule that can quickly diffuse through the alveoli into the blood and circulate throughout the body during breathing. ...
This research examined the effects of single-dose molecular hydrogen (H2) supplements on acid-base status and local muscle deoxygenation during rest, high-intensity intermittent training (HIIT) performance, and recovery. Ten healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg, containing 2.544 μg of H2) or H2-depleted placebo (1500 mg) supplements 1 h pre-exercise. They performed six bouts of 7 s all-out pedaling (HIIT) at 7.5% of body weight separated by 40 s pedaling intervals, followed by a recovery period. Blood gases' pH, PCO2, and HCO3 − concentrations were measured at rest. Muscle deoxygenation (deoxy[Hb + Mb]) and tissue O2 saturation (StO2) were determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF) muscles from rest to recovery. At rest, the HCP group had significantly higher PCO2 and HCO3 − concentrations and a slight tendency toward acidosis. During exercise, the first HIIT bout's peak power was significantly higher in HCP (839 ± 112 W) vs. Placebo (816 ± 108 W, p = 0.001), and HCP had a notable effect on significantly increased deoxy[Hb + Mb] concentration during HIIT exercise, despite no differences in heart rate response. The HCP group showed significantly greater O2 extraction in VL and micro-vascular (Hb) volume in RF during HIIT exercise. The HIIT exercise provided significantly improved blood flow and muscle reoxygenation rates in both the RF and VL during passive recovery compared to rest in all groups. The HCP supplement might exert ergogenic effects on high-intensity exercise and prove advantageous for improving anaerobic HIIT exercise performance.
Background
Inhalation of hydrogen gas (H 2 ) as an antioxidant supplement may alleviate exercise-induced oxidative damage and protect post-exercise hydrogen peroxide signaling, which may help mediate beneficial exercise adaptation. The aims of this study were to determine the effects of H 2 inhalation on plasma nitric oxide (NO) level and its synthesis precursor in professional athletes.
Methods
A randomized, placebo-controlled, double-blind, crossover trial was conducted with professional male rugby players for 3 weeks. Participants underwent 1 week of H 2 supplementation and 1 week of placebo treatment prior to daily sessions of high-intensity exercise training, separated by 1 week of low-intensity training as a washout.
Results
Two-way (supplementation and time) repeated-measures analyses of variance showed that NO, L-arginine, and tetrahydrobiopterin levels in the H 2 inhalation group were significantly higher than those in the placebo group after exercise (D6) and remained higher after 24 h of rest (D7). Levels of hydroxydeoxyguanosine and interleukin 6 were lower in the H 2 inhalation week than in the placebo week on D6 and D7. In addition, total antioxidant levels were significantly higher with H 2 inhalation than with placebo.
Significance
These results suggest that H 2 inhalation helps to maintain NO signaling after exercise and to alleviate inflammation and oxidative stress induced by high-intensity exercise training in professional athletes.
Moleküler hidrojen, düşük molekül ağırlıklı, polar olmayan, renksiz,
kokusuz bir gaz olup, fizikokimyasal ve fizyolojik özelliklere sahiptir.
Hidrojen; gaz, su içerisinde çözündürülerek hidrojenli zenginleştirilmiş
su (HZS), magnezyum (Mg) alkalisinden elde edilen gaz şeklinde gıda
zincirinde kullanılmaktadır. Hidrojen çevreye zarar vermeden, gıdada
meydana gelen olumsuzlukları asgari seviyeye düşürdüğü, gıdanın raf
ömrünün uzamasına katkı sağladığı ve gıda kalitesini koruduğu
bilinmektedir. Son zamanlarda ise hidrojenin gıda (yağ, süt, et vb.) üretim
prosesinin çeşitli aşamalarına kontrollü ve hızlı bir şekilde ilave edildiğini
gösteren çalışmaların sayısı sürekli artmaktadır. Bu bölümde hidrojenin
gıdalardaki potansiyel uygulamaları ve gıdalarda gözlemlenen etkilerin
neler olduğuna ilişkin son veriler ele alınmıştır.
The disruptions caused by ice crystal formation during the cryopreservation of cells and tissues can cause cell and tissue damage. Thus, preventing such damage during cryopreservation is an important but challenging goal. Here, a hibernating/awakening nanomotor with magnesium/palladium covering one side of a silica platform (Mg@Pd@SiO2) is proposed. This nanomotor is used in the cultivation of live NCM460 cells to demonstrate a new method to actively limit ice crystal formation and enable highly efficient cryopreservation. Cooling Mg@Pd@SiO2 in solution releases Mg²⁺/H2 and promotes the adsorption of H2 at multiple Pd binding sites on the cell surface to inhibit ice crystal formation and cell/tissue damage; additionally, the Pd adsorbs and stores H2 to form a hibernating nanomotor. During laser‐mediated heating, the hibernating nanomotor is activated (awakened) and releases H2, which further suppresses recrystallization and decreases cell/tissue damage. These hibernating/awakening nanomotors have great potential for promoting highly efficient cryopreservation by inhibiting ice crystal formation.
Molecular hydrogen shows antioxidant activity and distinct efficacy towards vascular diseases, but the understanding of this is not yet satisfactory at the atomic level. In this work, we study the binding properties of H2 to the heme group in relation with other diatomic molecules (DMs), including O2, NO and CO, and their displacement reactions, using first-principles calculations. We carry out molecular modeling of the heme group, using iron-porphyrin with the imidazole ligand, i.e., FePIm, and smaller models of Fe(CnHn+2N2)2NH3 with n = 3 and 1, and of molecular complexes of heme–DM and –H. Through analysis of optimized geometries and energetics, it is found that the order of binding strength of DMs or H to the Fe of heme is NO > O2 > CO > H > H2 for FePIm-based systems, while it is H > O2 > NO > CO > H2 for model-based systems. We calculate the activation energies for displacement reactions of H2 and H by other DMs, revealing that the H2 displacements occur spontaneously while the H displacements require a large amount of energy. Finally, our calculations corroborate that the rate constants increase with increasing temperature according to the Arrhenius relation.
Molecular hydrogen plays a role in modulating several cellular functions and in several diseases were documented its pleiotropic therapeutic effects. Several lines of evidence indicates that an important role in mechanisms involved in molecular hydrogen effects play modulation of cellular antioxidant defenses, including intracellular and extracellular redox signaling. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are involved in regulation of several cellular functions, in particular the modulation of extracellular matrix turnover. Moreover, oxidative stress-induced dysregulation of MMPs activities plays a crucial role in the development of pathological changes. Since it was described regulatory role of molecular hydrogen in modulation of several MMPs these enzymes represent potential targets of molecular hydrogen action. Our data demonstrated potential negative role of MMP-2 and MMP-28 in development of pathological changes induced by mediastinal irradiation (MI) of rats. Molecular hydrogen possessed beneficial effects against MI-induced changes in both matrix metalloproteinases. To the potential role of MMPs in protective effects of molecular hydrogen point also findings that inhalation of hydrogen-rich air was associated with protection against post-transplant complications and led to a partial reversal of MMP-9 activation. In conclusion, modulation of matrix metalloproteinases using molecular hydrogen could be promising strategy for treatment of several diseases, in which oxidative stress and tissue remodeling is an important partner.
In parallel with the development of nanoscience, nanomedicine and its branches were established. Its remarkable development is evidenced by milestones, awarded several times with Nobel prizes. Milestones also include the renaissance of molecular hydrogen therapy from 2007, which uses H2 as an effective antioxidant in preventive and therapeutic applications. In this chapter, in connection with the developed targeted delivery of drugs, we are dedicated to its modification in the form of local generation and release of hydrogen from nanocarriers such as nanoparticles, nanorods etc. The results are already reported in Alzheimer's disease and cancer treatment, wound healing, etc. Hydrogen therapy requires support and service which includes safe solid state storage of hydrogen to avoid potential explosions, where, in addition to hydrides such as MgH2, functionalized nanomaterials from the carbon family—as graphene or carbon nanotubes are applied. Attention must also be paid to the leakage of hydrogen and its presence in the environment, where nanosensors based on metal oxides and especially graphene-based sensors are the promising solution. Considering the numerous clinical trials and studies, H2 therapy can today be situated at the rise part of the Gartner’s cycle heading for the production plateau.
Molecular hydrogen (H2, dihydrogen) is an innovative experimental agent that could foster beneficial effects in a plethora of human conditions, including liver disorders. Recent trials demonstrated the positive effects of dihydrogen in several acute and chronic liver diseases, including chronic hepatitis B, non-alcoholic fatty liver disease, and liver cancer. Still, no systematic review or meta-analysis investigated the effects of dihydrogen intake on the hepatic function panel. For this report, we searched three relevant databases (PubMed, Web of Science, Scopus) from inception until December 24, 2022, using PRISMA guidelines. A literature search yielded 365 publications in total. After removing duplicates and studies that did not meet the inclusion criteria, 12 studies (published from 2008 to 2022) were included in this analysis. We found that serum malondialdehyde levels were significantly decreased following dihydrogen intake (pooled standardized mean difference = − 0.97 [95% confidence interval [CI], from − 1.65 to − 0.19; P = 0.01), with results indicating a large effect of dihydrogen intervention. A strong trend for a reduction in the liver function tests (including aspartate aminotransferase and alanine transaminase) has also been observed after dihydrogen administration (P < 0.20). Our findings suggested that dihydrogen can favorably affect the hepatic function panel; additional well-sampled interventional trials are highly warranted to corroborate our results.
Ageing is an inevitable process that increases the probability of chronic disease that involves an evolving decline in organism function over time. The length of human life is closely related to ageing, which can cause a deterioration of physiological functions and lead to the development of various chronic diseases. Many theories have been put forward to illustrate the ageing mechanisms, with the free oxidative stress theory being the most well-known. Aging is caused by the excessive accumulation of cells or tissues related to oxidative damage caused by ROS. As everyone knows that oxidative stress is closely related to aging, antioxidants may be potentially valuable in the treatment of senescence disease. Hydrogen (H2) is a colorless, tasteless small molecule that plays a major role in eliminating harmful free radicals and reducing oxidative damage in vivo, such as anti-oxidation, anti-inflammation, and anti-apoptosis. Additionally, H2 can be utilized to prevent and cure several aging-related diseases, including cancer, Alzheimer’s disease, and gastrointestinal diseases. Understanding the aging process is crucial for comprehending how to slow the aging process and the development of aging-related diseases. This chapter summarized the preventive and treatment applications of molecular H2 in anti-ageing and underlying mechanisms in aging-related diseases.
Background:
Lung contusion caused by blunt chest trauma evokes a severe inflammatory reaction in the pulmonary parenchyma that may be associated with acute respiratory distress syndrome. Although hydrogen gas has antioxidant and anti-inflammatory effects and is protective against multiple types of lung injury at safe concentrations, the effects of inhaled hydrogen gas on blunt lung injury have not been previously investigated. Therefore, using a mouse model, we tested the hypothesis that hydrogen inhalation after chest trauma would reduce pulmonary inflammation and acute lung injury associated with lung contusion.
Methods:
Inbred male C57BL/6 mice were randomly divided into 3 groups: sham with air inhalation, lung contusion with air inhalation, and lung contusion with 1.3% hydrogen inhalation. Experimental lung contusion was induced using a highly reproducible and standardized apparatus. Immediately after induction of lung contusion, mice were placed in a chamber exposed to 1.3% hydrogen gas in the air. Histopathological analysis and real-time polymerase chain reaction in lung tissue and blood gas analysis were performed 6 hours after contusion.
Results:
Histopathological examination of the lung tissue after contusion revealed perivascular/intra-alveolar hemorrhage, perivascular/interstitial leukocyte infiltration, and interstitial/intra-alveolar edema. These histological changes and the extent of lung contusion, as determined by computed tomography, were significantly mitigated by hydrogen inhalation. Hydrogen inhalation also significantly reduced inflammatory cytokine and chemokine mRNA levels and improved oxygenation.
Conclusion:
Hydrogen inhalation therapy significantly mitigated inflammatory responses associated with lung contusion in mice. Hydrogen inhalation therapy may be a supplemental therapeutic strategy for treating lung contusion.
Background:
Activated inflammatory cells produce reactive oxygen species (ROS) to eliminate pathogens. Under normal conditions, the pathogens are taken care of, and tissues are repaired. However, in periodontal disease, persistent inflammation causes increased ROS release and impaired healing. Therefore, removal of overproduced ROS using antioxidants is necessary. Hydrogen water has an antioxidative effect on cells and impedes oxidative stress-related disorders.
Aim:
To study the effect of hydrogen water on cell viability, migration, and its antioxidative potential in fibroblasts obtained from chronic periodontitis patients.
Materials and methods:
The gingival tissue samples were obtained from 26 subjects (13 periodontally healthy individuals and 13 chronic periodontitis patients) and processed. The human gingival fibroblasts were cultured and the assays were commenced once adequate growth was detected. The effect of hydrogen water on cell viability was checked by neutral red assay, while the migration potential was assessed by transwell migration assay. The antioxidative potential of hydrogen water was evaluated by CUPRAC assay.
Statistical analysis:
Intergroup comparison was done using Mann-Whitney U-test. Intragroup comparison was done using Wilcoxon signed-rank test.
Results:
Hydrogen water was nontoxic to the fibroblasts at 24 h and 48 h. The intergroup comparison of the cell viability between hydrogen water-treated periodontally healthy gingival fibroblasts (HF) and fibroblasts from patients with chronic periodontitis (CF) showed a statistically significant (P = 0.00) difference at 24 h and 48 h. Hydrogen water also positively influenced the migratory capacity. Hydrogen water-treated fibroblasts obtained from chronic periodontitis patients showed more migration in comparison to the healthy group (P = 0.00). Hydrogen water showed an antioxidative potential. The maximum potential was seen in relation to the fibroblasts obtained from chronic periodontitis patients at 48 h.
Conclusion:
Hydrogen water was nontoxic, increased the migratory capacity, and showed an antioxidative potential on human fibroblasts obtained from periodontally healthy individuals and patients with chronic periodontitis.
Iron is the trace element of natural selection by the biological systems due to its versatile coordination chemistry, and is recently explored for medicinal and diagnostic applications. Photo-activated states of iron complexes exhibiting substitution, dissociation, isomerization reactions, intramolecular redox reactions or energy transfer to other molecules have attracted the attention across the globe for the potent applications in photo-chemotherapy. There is a significant advancement on the development of iron-based complexes for photochemotherapeutic applications. Here in we reviewed the photo-activated states and photochemistry of iron complexes, and recent advances made in the area of photochemotherapy of iron complexes relevant to the photochemistry of iron complexes.
Birth asphyxia can cause moderate to severe brain injury. It is unclear to what degree apoptotic or necrotic mechanisms of cell death account for damage after neonatal hypoxia-ischemia (HI). In a 7-d-old rat HI model, we determined the contributions of apoptosis and necrosis to neuronal injury in adjacent Nissl-stained, hematoxylin and eosin-stained, and terminal deoxynucleotidyl transferase-mediated UTP nick end-labeled sections. We found an apoptotic-necrotic continuum in the morphology of injured neurons in all regions examined. Eosinophilic necrotic neurons, typical in adult models, were rarely observed in neonatal HI. Electron microscopic analysis showed "classic" apoptotic and necrotic neurons and "hybrid" cells with intermediate characteristics. The time course of apoptotic injury varied regionally. In CA3, dentate gyrus, medial habenula, and laterodorsal thalamus, the density of apoptotic cells was highest at 24-72 hr after HI and then declined. In contrast, densities remained elevated from 12 hr to 7 d after HI in most cortical areas and in the basal ganglia. Temporal and regional patterns of neuronal death were compared with expression of caspase-3, a cysteine protease involved in the execution phase of apoptosis. Immunocytochemical and Western blot analyses showed increased caspase-3 expression in damaged hemispheres 24 hr to 7 d after HI. A p17 peptide fragment, which results from the proteolytic activation of the caspase-3 precursor, was detected in hippocampus, thalamus, and striatum but not in cerebral cortex. The continued expression of activated caspase-3 and the persistence of cells with an apoptotic morphology for days after HI suggests a prolonged role for apoptosis in neonatal hypoxic ischemic brain injury.
This paper presents a composition method for stack-attributed tree transducers. Stackattributed tree transducers extend attributed tree transducers with a pushdown stack device for attribute values. Stack-attributed tree transducers are more powerful than attributed tree transducers due to the stack mechanism. We extend the existing composition method for attributed tree transducers to the composition method for stack-attributed tree transducers. The composition method is proved to be correct and to enjoy a closure property.
Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5-2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55-0.65 mM), by the following chemical reaction; Mg + 2H(2)O --> Mg (OH)(2) + H(2). The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome. The portable magnesium stick was a safe, easy and effective method of delivering hydrogen rich water for daily consumption by participants in the study.
Background:
Small intestinal bacterial overgrowth (SIBO) is a condition in which excessive levels of bacteria, mainly the colonic-type species are present in the small intestine. Recent data suggest that SIBO may contribute to the pathophysiology of Irritable bowel syndrome (IBS). The purpose of this study was to identify potential predictors of SIBO in patients with IBS.
Methods:
Adults with IBS based on Rome II criteria who had predominance of bloating and flatulence underwent a glucose breath test (GBT) to determine the presence of SIBO. Breath samples were obtained at baseline and at 30, 45, 60, 75 and 90 minutes after ingestion of 50 g of glucose dissolved in 150 mL of water. Results of the glucose breath test, which measures hydrogen and methane levels in the breath, were considered positive for SIBO if 1) the hydrogen or methane peak was >20 ppm when the baseline was <10 ppm, or 2) the hydrogen or methane peak increased by 12 ppm when baseline was >or=10 ppm.
Results:
Ninety-eight patients were identified who underwent a GBT (mean age, 49 y; 78% female). Thirty-five patients (36%) had a positive GBT result suggestive of SIBO. A positive GBT result was more likely in patients >55 years of age (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4-9.0) and in females (OR, 4.0; 95% CI, 1.1-14.5). Hydrogen was detected more frequently in patients with diarrhea-predominant IBS (OR, 8; 95% CI, 1.4-45), and methane was the main gas detected in patients with constipation-predominant IBS (OR, 8; 95% CI, 1.3-44). There was no significant correlation between the presence of SIBO and the predominant bowel pattern or concurrent use of tegaserod, proton pump inhibitors, or opiate analgesics.
Conclusions:
Small intestinal bacterial overgrowth was present in a sizeable percentage of patients with IBS with predominance of bloating and flatulence. Older age and female sex were predictors of SIBO in patients with IBS. Identification of possible predictors of SIBO in patients with IBS could aid in the development of successful treatment plans.
It has been demonstrated that hydrogen can selectively reduce hydroxyl and peroxynitrite in vitro. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, this study was designed to test the hypothesis that hydrogen may be an effective radioprotective agent. This paper demonstrates that treating cells with hydrogen before irradiation could significantly inhibit ionizing irradiation(IR)-induced Human Lymphocyte AHH-1 cells apoptosis and increase cells viability in vitro. This paper also shows that hydrogen can protect gastrointestinal endothelia from radiation-induced injury, decrease plasma malondialdehyde (MDA) intestinal 8-hydroxydeoxyguanosine (8-OHDG) levels and increase plasma endogenous antioxidants in vivo. It is suggested that hydrogen has a potential as an effective and safe radioprotective agent.
Retinal ischemia-reperfusion (I/R) injury by transient elevation of intraocular pressure (IOP) is known to induce neuronal damage through the generation of reactive oxygen species. Study results have indicated that molecular hydrogen (H(2)) is an efficient antioxidant gas that selectively reduces the hydroxyl radical (*OH) and suppresses oxidative stress-induced injury in several organs. This study was conducted to explore the neuroprotective effect of H(2)-loaded eye drops on retinal I/R injury.
Retinal ischemia was induced in rats by raising IOP for 60 minutes. H(2)-loaded eye drops were prepared by dissolving H(2) gas into a saline to saturated level and administered to the ocular surface continuously during the ischemia and/or reperfusion periods. One day after I/R injury, apoptotic cells in the retina were quantified, and oxidative stress was evaluated by markers such as 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine. Seven days after I/R injury, retinal damage was quantified by measuring the thickness of the retina.
When H(2)-loaded eye drops were continuously administered, H(2) concentration in the vitreous body immediately increased and I/R-induced *OH level decreased. The drops reduced the number of retinal apoptotic and oxidative stress marker-positive cells and prevented retinal thinning with an accompanying activation of Müller glia, astrocytes, and microglia. The drops improved the recovery of retinal thickness by >70%.
H(2) has no known toxic effects on the human body. Thus, the results suggest that H(2)-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury.
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.
While it is well established that stroke and cerebral hypoperfusion are risk factors for Alzheimer's disease (AD), the molecular link between ischemia/hypoxia and amyloid precursor protein (APP) processing has only been recently established. Here we review the role of the release of reactive oxygen species (ROS) by the mitochondrial electron chain in response to hypoxia, providing evidence that hypoxia fosters the amyloidogenic APP processing through a biphasic mechanism that up-regulates Beta-secretase activity, which involves an early release of ROS and an activation of HIF-1Alpha.
Cisplatin is a widely used anti-cancer drug in the treatment of a wide range of tumors; however, its application is limited by nephrotoxicity, which is affected by oxidative stress. We have reported that molecular hydrogen (H(2)) acts as an efficient antioxidant (Ohsawa et al. in Nat Med 13:688-694, 2007). Here we show that hydrogen efficiently mitigates the side effects of cisplatin by reducing oxidative stress.
Mice were administered cisplatin followed by inhaling hydrogen gas (1% H(2) in air). Furthermore, instead of inhaling hydrogen gas, we examined whether drinking water containing hydrogen (hydrogen water; 0.8 mM H(2) in water) is applicable by examining oxidative stress, mortality, and body-weight loss. Nephrotoxicity was assessed by morphological changes, serum creatinine and blood urea nitrogen (BUN) levels.
Inhalation of hydrogen gas improved mortality and body-weight loss caused by cisplatin, and alleviated nephrotoxicity. Hydrogen was detected in blood when hydrogen water was placed in the stomach of a rat. Consuming hydrogen water ad libitum also reduced oxidative stress, mortality, and body-weight loss induced by cisplatin in mice. Hydrogen water improved metamorphosis accompanying decreased apoptosis in the kidney, and nephrotoxicity as assessed by serum creatinine and BUN levels. Despite its protective effects against cisplatin-induced toxicity, hydrogen did not impair anti-tumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo.
Hydrogen has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the side effects of cisplatin.
Respiratory muscle weakness resulting from both diaphragmatic contractile dysfunction and atrophy has been hypothesized to contribute to the weaning difficulties associated with prolonged mechanical ventilation (MV). While it is clear that oxidative injury contributes to MV-induced diaphragmatic weakness, the source(s) of oxidants in the diaphragm during MV remain unknown. These experiments tested the hypothesis that xanthine oxidase (XO) contributes to MV-induced oxidant production in the rat diaphragm and that oxypurinol, a XO inhibitor, would attenuate MV-induced diaphragmatic oxidative stress, contractile dysfunction, and atrophy. Adult female Sprague-Dawley rats were randomly assigned to one of six experimental groups: 1) control, 2) control with oxypurinol, 3) 12 h of MV, 4) 12 h of MV with oxypurinol, 5) 18 h of MV, or 6) 18 h of MV with oxypurinol. XO activity was significantly elevated in the diaphragm after MV, and oxypurinol administration inhibited this activity and provided protection against MV-induced oxidative stress and contractile dysfunction. Specifically, oxypurinol treatment partially attenuated both protein oxidation and lipid peroxidation in the diaphragm during MV. Further, XO inhibition retarded MV-induced diaphragmatic contractile dysfunction at stimulation frequencies >60 Hz. Collectively, these results suggest that oxidant production by XO contributes to MV-induced oxidative injury and contractile dysfunction in the diaphragm. Nonetheless, the failure of XO inhibition to completely prevent MV-induced diaphragmatic oxidative damage suggests that other sources of oxidant production are active in the diaphragm during prolonged MV.
The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III)1 identified the metabolic syndrome as a multiplex risk factor for cardiovascular disease (CVD) that is deserving of more clinical attention. The cardiovascular community has responded with heightened awareness and interest. ATP III criteria for metabolic syndrome differ somewhat from those of other organizations. Consequently, the National Heart, Lung, and Blood Institute, in collaboration with the American Heart Association, convened a conference to examine scientific issues related to definition of the metabolic syndrome. The scientific evidence related to definition was reviewed and considered from several perspectives: (1) major clinical outcomes, (2) metabolic components, (3) pathogenesis, (4) clinical criteria for diagnosis, (5) risk for clinical outcomes, and (6) therapeutic interventions.
ATP III viewed CVD as the primary clinical outcome of metabolic syndrome. Most individuals who develop CVD have multiple risk factors. In 1988, Reaven2 noted that several risk factors (eg, dyslipidemia, hypertension, hyperglycemia) commonly cluster together. This clustering he called Syndrome X , and he recognized it as a multiplex risk factor for CVD. Reaven and subsequently others postulated that insulin resistance underlies Syndrome X (hence the commonly used term insulin resistance syndrome ). Other researchers use the term metabolic syndrome for this clustering of metabolic risk factors. ATP III used this alternative term. It avoids the implication that insulin resistance is the primary or only cause of associated risk factors. Although ATP III identified CVD as the primary clinical outcome of the metabolic syndrome, most people with this syndrome have insulin resistance, which confers increased risk for type 2 diabetes. When diabetes becomes clinically apparent, CVD risk rises sharply. Beyond CVD and type 2 diabetes, individuals with metabolic syndrome seemingly are susceptible to other conditions, notably polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some …
Context The Third Report of the National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (ATP III) highlights the importance of treating patients with the metabolic
syndrome to prevent cardiovascular disease. Limited information is available
about the prevalence of the metabolic syndrome in the United States, however.Objective To estimate the prevalence of the metabolic syndrome in the United States
as defined by the ATP III report.Design, Setting, and Participants Analysis of data on 8814 men and women aged 20 years or older from the
Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional
health survey of a nationally representative sample of the noninstitutionalized
civilian US population.Main Outcome Measures Prevalence of the metabolic syndrome as defined by ATP III (≥3 of
the following abnormalities): waist circumference greater than 102 cm in men
and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69
mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL
(1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of
at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).Results The unadjusted and age-adjusted prevalences of the metabolic syndrome
were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among
participants aged 20 through 29 years to 43.5% and 42.0% for participants
aged 60 through 69 years and aged at least 70 years, respectively. Mexican
Americans had the highest age-adjusted prevalence of the metabolic syndrome
(31.9%). The age-adjusted prevalence was similar for men (24.0%) and women
(23.4%). However, among African Americans, women had about a 57% higher prevalence
than men did and among Mexican Americans, women had about a 26% higher prevalence
than men did. Using 2000 census data, about 47 million US residents have the
metabolic syndrome.Conclusions These results from a representative sample of US adults show that the
metabolic syndrome is highly prevalent. The large numbers of US residents
with the metabolic syndrome may have important implications for the health
care sector.
We studied the role of reactive oxygen intermediates (ROls) in experimental liver metastasis induced in mice by the inoculation of COLON 26-M5 murine colon cancer cells, a highly metastatic variant of COLON 26 cells, and the effect of ROIs on the invasive capacity of the cells in an in vitro chemo-invasion assay model using reconstituted basement membrane matrigel. We also measured the release of ROIs from cells using electron spin resonance (ESR) spectrometry. Hydroxyl radicals (.OH) were constitutively released from the cells. This release was augmented by pre-treatment with phorbol 12-myristate 13-acetate (PMA). In experimental liver metastasis in CDF1 mice, the administration of recombinant human superoxide dismu-tase (r-hSOD) significantly increased the number of metastatic nodules, while administration of catalase significantly inhibited metastasis formation. In vitro pre-treatment of cells with PMA significantly increased the number of metastatic nodules. Invasive capacity of the cells was markedly augmented by pre-treatment with PMA. PMA-induced augmentation was significantly inhibited by the simultaneous addition of r-hSOD to the assay. Catalase had no significant effect. Our findings suggest that ROIs play an important role in tumor invasion and metastasis, and that hydrogen peroxide (H2O2) may contribute to the retention or extravasation of circulating tumor cells. Furthermore, the superoxide anion (O2-) released by tumor cells may play an important role in basement membrane degradation.
The pathogenesis of chronic rejection likely involves an interplay between immunogenic and nonimmunogenic factors. The objective of this study was to determine the influence of cold ischemic preservation injury on the rate of progression to chronic rejection in the Lewis to F344 cardiac allograft model.
To induce an ischemic injury, donor hearts were stored for 3 hr at 4 degrees C in University of Wisconsin solution before transplantation. Allografts were excised at 1, 7, and 90 days after transplantation or at rejection. Vasculopathy was graded for degree of intimal thickening based on the involvement of vascular perimeter and luminal compromise.
The degree of vessel injury in ischemic injured allografts at 90 days was significantly greater than in nonischemic injured allografts (2.8+/-0.4 vs. 1.6+/-0.5, P<0.05). Ischemic injury in syngeneic grafts did not induce a vasculopathy. Immunoperoxidase staining with R73 (anti-T cell) and ED1 (anti-macrophage) monoclonal antibodies revealed that, in ischemic injured allografts at 90 days after transplantation, the infiltrate was composed predominantly of T cells and macrophages. Additionally, ischemic injured allografts excised at 7 days after transplantation showed cellular infiltrates composed of R73-positive T cells and rare interleukin-2 receptor-positive cells, which was not observed in nonischemic allografts or ischemic syngeneic grafts.
The progression to chronic vasculopathy in this model is principally an immunologic process, which is accelerated by an ischemic insult to the allograft. The vascular injury is mediated in part by T cells and macrophages.
By its antioxidant effect, molecular hydrogen gas (H2) was reported to protect organs from tissue damage induced by ischemia reperfusion. To evaluate its anti-inflammatory effects, we established a mouse model of human inflammatory bowel disease (IBD) by supplying mice with water containing (1) dextran sodium sulfate (DSS) (5%), (2) DSS (5%) and H2, or (3) H2 only ad libitum up to 7 days. At day-7, DSS-induced pathogenic outcomes including, loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of IL-12, TNF-α and IL-1β in colon lesion, were significantly suppressed by the addition of H2 to DSS solution. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice.
It is well known that some intestinal bacteria, such as Escherichia coli, can produce a remarkable amount of molecular hydrogen (H2). Although the antioxidant effects of H2 are well documented, the present study examined whether H2 released from intestinally colonized bacteria could affect Concanavalin A (ConA)-induced mouse hepatitis. Systemic antibiotics significantly decreased the level of H2 in both liver and intestines along with suppression of intestinal bacteria. As determined by the levels of AST, ALT, TNF-α and IFN-γ in serum, suppression of intestinal bacterial flora by antibiotics increased the severity of ConA-induced hepatitis, while reconstitution of intestinal flora with H2-producing E. coli, but not H2-deficient mutant E. coli, down-regulated the ConA-induced liver inflammation. Furthermore, in vitro production of both TNF-α and IFN-γ by ConA-stimulated spleen lymphocytes was significantly inhibited by the introduction of H2. These results indicate that H2 released from intestinal bacteria can suppress inflammation induced in liver by ConA.
Oxidative stress is implicated in atherogenesis; however most clinical trials with dietary antioxidants failed to show marked success in preventing atherosclerotic diseases. We have found that hydrogen (dihydrogen; H2) acts as an effective antioxidant to reduce oxidative stress [I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki, K. Yamagata, K. Katsura, Y. Katayama, S, Asoh, S. Ohta, Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals, Nat. Med. 13 (2007) 688–694]. Here, we investigated whether drinking H2-dissolved water at a saturated level (H2–water) ad libitum prevents arteriosclerosis using an apolipoprotein E knockout mouse (apoE−/−), a model of the spontaneous development of atherosclerosis. ApoE−/− mice drank H2–water ad libitum from 2 to 6 month old throughout the whole period. Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis.
Protective effect of hydrogen (H(2)) gas on cardiac ischemia-reperfusion (I/R) injury has been demonstrated previously. This study was designed to test the hypothesis that hydrogen-rich saline (saline saturated with molecular hydrogen), which is easy to use, induces cardioprotection against ischemia (30 min) and reperfusion (24 h) injury in rats. Adult male Sprague-Dawley rats underwent 30-min occlusion of the left anterior descending (LAD) coronary artery and 24-h reperfusion. Intraperitoneal injection of hydrogen-rich saline before reperfusion significantly decreased plasma and myocardium malondialdehyde (MDA) concentration, decreased cardiac cell apoptosis, and myocardial 8-hydroxydeoxyguanosine (8-OHdG) in area at risk zones (AAR), suppressed the activity of caspase-3, and reduced infarct size. The heart function parameters including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), +(dP/dt)(max) and -(dP/dt)(max) were also significantly improved 24 h after reperfusion. It is concluded that hydrogen-rich saline is a novel, simple, safe, and effective method to attenuate myocardial I/R injury.
Protective effect of hydrogen (H(2)) gas on cardiac ischemia-reperfusion (I/R) injury has been demonstrated previously. This study was designed to test the hypothesis that hydrogen-rich saline (saline saturated with molecular hydrogen), which is easy to use, induces cardioprotection against ischemia (30 min) and reperfusion (24 h) injury in rats. Adult male Sprague-Dawley rats underwent 30-min occlusion of the left anterior descending (LAD) coronary artery and 24-h reperfusion. Intraperitoneal injection of hydrogen-rich saline before reperfusion significantly decreased plasma and myocardium malondialdehyde (MDA) concentration, decreased cardiac cell apoptosis, and myocardial 8-hydroxydeoxyguanosine (8-OHdG) in area at risk zones (AAR), suppressed the activity of caspase-3, and reduced infarct size. The heart function parameters including left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), +(dP/dt)(max) and -(dP/dt)(max) were also significantly improved 24 h after reperfusion. It is concluded that hydrogen-rich saline is a novel, simple, safe, and effective method to attenuate myocardial I/R injury. Exp Biol Med 234:1212-1219, 2009
Hydrogen has been reported to selectively reduce the hydroxyl radical, the most cytotoxic of reactive oxygen species. In this study we investigated the effects of hydrogen-rich saline on the prevention of lung injury induced by intestinal ischemia/reperfusion (I/R) in rats.
Male Sprague-Dawley rats (n=30, 200-220g) were divided randomly into three experimental groups: sham operated, intestinal I/R plus saline treatment (5ml/kg, i.v.), and intestinal I/R plus hydrogen-rich saline treatment (5ml/kg, i.v.) groups. Intestinal I/R was produced by 90min of intestinal ischemia followed by a 4h of reperfusion.
Hydrogen-rich saline treatment decreased the neutrophil infiltration, the lipid membrane peroxidation, NF-kappaB activation and the pro-inflammatory cytokine interleukin IL-1beta and TNF-alpha in the lung tissues compared with those in saline-treated rat.
Hydrogen-rich saline attenuates lung injury induced by intestinal I/R.
Background:
Hydrogen has been considered as a novel antioxidant that prevents injuries resulted from ischemia-reperfusion (I/R) injury in various tissues. The study was designed to determine the effect of hydrogen-rich saline on the smooth muscle contractile response to KCl, and on epithelial proliferation and apoptosis of intestine subjected to I/R.
Methods:
Intestinal I/R injury was induced in Sprague-Dawley rats using bulldog clamps in superior mesenteric artery by 45 min ischemia followed by 1 h reperfusion. Rats were divided randomly into four groups: sham-operated, I/R, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment groups. Hydrogen-rich saline (>0.6 mM, 6 mL/kg) or saline (6 mL/kg) was administered, respectively, via tail vein 30 min prior to reperfusion. Following reperfusion, segments of terminal jejunum were rapidly taken and transferred into isolated organ bath and responses to KCl were recorded. Samples of terminal jejunum were also taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in intestinal epithelium was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression and distribution of proliferating cell nuclear antigen (PCNA) were detected with immunohistochemistry.
Results:
Hydrogen-rich saline treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis, and promoting enterocytes proliferation. Moreover, Hydrogen-rich saline treatment significantly limited the neutrophil infiltration, lipid oxidation, and ameliorated the decreased contractility response to KCl in the intestine subjected to I/R.
Conclusions:
These results suggest that hydrogen treatment has a protective effect against intestinal contractile dysfunction and damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis, and to promote epithelial cell proliferation.
Hypoxia-ischemia (HI) brain injury is a major cause of neuronal cell death especially apoptosis in the perinatal period. This study was designated to examine the effect of hydrogen therapy on apoptosis in an established neonatal HI rat pup model. Seven-day-old rat pups were subjected to left common carotid artery ligation and then 90 min hypoxia (8% oxygen at 37 C). Immediately after HI insult, pups were placed into a chamber filled with 2% H(2) for 30 min, 60 min, or 120 min, respectively. 24 h after 2% H2 therapy, the pups were decapitated and brain injury was assessed by 2,3,5-triphenyltetrazoliumchloride (TTC), Nissl, and TUNEL staining, as well as caspase-3, caspase-12 activities in the cortex and hippocampus. H(2) treatment in a duration-dependent manner significantly reduced the number of positive TUNEL cells and suppressed caspase-3 and -12 activities. These results indicated H(2) administration after HI appeared to provide brain protection via inhibition of neuronal apoptosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
Hydrogen selectively reduces levels of hydroxyl radicals and alleviates acute oxidative stress in many models. Hydrogen-rich saline provides a high concentration of hydrogen that can be easily and safely applied.
In this study, we investigated the effects of hydrogen-rich saline on the prevention of liver injury induced by obstructive jaundice in rats.
Male Sprague-Dawley rats (n=56) were divided randomly into four experimental groups: sham operated, bile duct ligation (BDL) plus saline treatment [5 ml/kg, intraperitoneal (i.p.)], BDL plus low-dose hydrogen-rich saline treatment (5 ml/kg, i.p.) and BDL plus high-dose hydrogen-rich saline treatment (10 ml/kg, i.p.).
The liver damage was evaluated microscopically 10 days after BDL. Serum alanine aminotransferase and aspartate aminotransferase levels, tissue malondialdehyde content, myeloperoxidase activity, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6 and high-mobility group box 1 levels were all increased significantly by BDL. Hydrogen-rich saline reduced levels of these markers and relieved morphological liver injury. Additionally, hydrogen-rich saline markedly increased the activities of anti-oxidant enzymes superoxide dismutase and catalase and downregulated extracellular signal-regulated protein kinase (ERK)1/2 activation.
Hydrogen-rich saline attenuates BDL-induced liver damage, possibly by the reduction of inflammation and oxidative stress and the inhibition of the ERK1/2 pathway.
In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.
Hydrogen-dissolved water has been suggested to be effective for alleviating the oxidative stress. In the present study, neutral-pH hydrogen-enriched electrolyzed water (NHE-water; dissolved hydrogen: 0.90-1.14 parts per million [ppm]; oxido-reduced potential: -150 approximately -80 mV), which was prepared with a water-electrolysis apparatus equipped with a non-diaphragm cell and a highly compressed activated-carbon block, was evaluated for the mutagenic and genotoxic potentials, at concentrations up to 100% dose/plate, and for the subchronic toxicity. NHE-water did not induce reverse mutations in Salmonella typhimurium strains TA100, TA1535, TA98 and TA1537, and Escherichia coli strain WP2uvrA, in either the absence or presence of rat liver S9 for exogenous metabolic activation. Similarly, NHE-water did not induce chromosome aberrations in Chinese hamster lung fibroblast cells (CHL/IU), in short-term (6-hour) tests, with or without rat liver S9, or in a continuous treatment (24-hour) test. To evaluate the subchronic toxicity, Crj:CD(SD) specific pathogen free (SPF)-rats were administered with NHE-water at a dose of 20 mL/kg/day for 28 days via intragastric infusion. NHE-water-related toxic changes were not seen in terms of any items such as clinical symptoms, body weight, food consumption, urinalysis, hematology, blood chemistry, necropsy, each organ weight and histopathology. Thus, the no-observable-adverse-effect level (NOAEL) for NHE-water was estimated to be greater than 20 mL/kg/day under the conditions examined, demonstrating the consistency with the expected safety for a human with a body weight of 60 kg to drink the NHE-water up to at least 1.2 L/day.
This study is to examine if hydrogen-rich saline reduced amyloid beta (Abeta) induced neural inflammation, and learning and memory deficits in a rat model. S-D male rats (n=84, 280-330g) were divided into three groups, sham-operated, Abeta1-42 injected and Abeta1-42 plus hydrogen-rich saline-treated animals. Hydrogen-rich saline (5ml/kg, i.p., daily) was injected for 14days after intracerebroventricular injection of Abeta1-42. The levels of MDA, IL-6 and TNF-alpha were assessed by biochemical and ELISA analysis. Morris Water Maze and open field task were used to assess the memory dysfunction and motor dysfunction, respectively. LTP were used to detect the electrophysiology changes, HNE and GFAP immunohistochemistry were used to assess the oxidative stress and glial cell activation. After Abeta1-42 injection, the levels of MDA, IL-6, and TNF-alpha were increased in brain tissues and hydrogen-rich saline treatment suppressed MDA, IL-6, and TNF-alpha concentration. Hydrogen-rich saline treatment improved Morris Water Maze and enhanced LTP in hippocampus blocked by Abeta1-42. Furthermore, hydrogen-rich saline treatment also decreased the immunoreactivitiy of HNE and GFAP in hippocampus induced by Abeta1-42. In conclusion, hydrogen-rich saline prevented Abeta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.
Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the l-arginine (l-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of l-Arg, each at concentrations of 250mg/100g body weight, with an interval of 1h. Hydrogen-rich saline (>0.6mM, 6ml/kg) or saline (6ml/kg) was administered, respectively, via tail vein 15min after each l-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-kappaB) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of l-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-kappaB activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-kappaB activation and to promote acinar cell proliferation.
Cardinal and colleagues describe the use of molecular hydrogen, the most abundant molecule in the universe, as a treatment for chronic allograft nephropathy (CAN) in a rat model of kidney transplantation.