Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation.

Inhalation of hydrogen (H2) gas is therapeutically effective for cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders including pathologies induced by anesthetic gases. To understand the mechanisms underlying the protective effects of H2 on the brain, we investigated the molecular signals affected by H2 in sevoflurane-induced neuronal cell death. We confirmed that neural progenitor cells are susceptible to sevoflurane and undergo apoptosis in the retrosplenial cortex of neonatal mice. Co-administration of 1-8% H2 gas for 3 h to sevoflurane-exposed pups suppressed elevated caspase-3-mediated apoptotic cell death and concomitantly decreased c-Jun phosphorylation and activation of the c-Jun pathway, all of which are induced by oxidative stress. Anesthesia-induced increases in lipid peroxidation and oxidative DNA damage were alleviated by H2 inhalation. Phosphoproteome analysis revealed enriched clusters of differentially phosphorylated proteins in the sevoflurane-exposed neonatal brain that included proteins involved in neuronal development and synaptic signaling. H2 inhalation modified cellular transport pathways that depend on hyperphosphorylated proteins including microtubule-associated protein family. These modifications may be involved in the protective mechanisms of H2 against sevoflurane-induced neuronal cell death.

H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

Effects of Molecular Hydrogen in the Pathophysiology and Management of Cardiovascular and Metabolic Diseases.

Diet and lifestyle choices, notably the Western-type diet, are implicated in oxidative stress and inflammation, factors that elevate the risk of cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM). In contrast, the Mediterranean of diet, rich in antioxidants, appears to have protective effects against these risks. This article highlights the dual role of diet in generating molecular hydrogen ( H 2 ) in the gut, and H 2 's subsequent influence on the pathophysiology and prevention of CVD and T2DM. Dietary fiber, flavonoids, and probiotics contribute to the production of liters of H 2 in the gut, functioning as antioxidants to neutralize free radicals and dampen inflammation. In the last two decades, mounting evidence has demonstrated that both endogenously produced and exogenously administered H 2 , whether via inhalation or H 2 -rich water (HRW), have potent anti-inflammatory effects across a wide range of biochemical and pathophysiological processes. Recent studies indicate that H 2 can neutralize hydroxyl and nitrosyl radicals, acting as a cellular antioxidant, thereby reducing oxidative stress and inflammation-leading to a significant decline in CVDs and metabolic diseases. Clinical and experimental research support the therapeutic potential of H 2 interventions such as HRW in managing CVDs and metabolic diseases. However, larger studies are necessary to verify the role of H 2 therapy in the management of these chronic diseases.

Competition between Loss of H2 versus H+H in the Fragmentation of the Fluorene Cation.

The fluorene cation is a frequently studied molecule in the context of fragmentation experiments. This is because of its potential role in interstellar chemistry, notably as a precursor of PAH cages. In this paper, we analyze H, H+ , H2 and H 2 + ${{\rm{H}}_2^ + }$ losses from the fluorene cation using the SMF (Statistical Molecular Fragmentation) model. We calculate the probabilities of all the 534 possible fragmentation channels as a function of the excitation energy, up to the loss of three hydrogens. Four different types of hydrogen atom pairings (from the same carbon, from the same ring, from different rings and across-the-bay) have been tested in order to determine which types contribute to the actual production of hydrogen molecules. The simulated breakdown curves are in very good agreement with different experimental results when same ring pairing is taken into account. It was possible to deduce from the model the locations of the emitted H, H+ , H2 and H 2 + ${{\rm{H}}_2^ + }$ species.

Hydrogen therapy as a potential therapeutic intervention in heart disease: from the past evidence to future application.

Cardiovascular disease is the leading cause of mortality worldwide. Excessive oxidative stress and inflammation play an important role in the development and progression of cardiovascular disease. Molecular hydrogen, a small colorless and odorless molecule, is considered harmless in daily life when its concentration is below 4% at room temperature. Owing to the small size of the hydrogen molecule, it can easily penetrate the cell membrane and can be metabolized without residue. Molecular hydrogen can be administered through inhalation, the drinking of hydrogen-rich water, injection with hydrogen-rich-saline, and bathing of an organ in a preservative solution. The utilization of molecular hydrogen has shown many benefits and can be effective for a wide range of purposes, from prevention to the treatment of diseases. It has been demonstrated that molecular hydrogen exerts antioxidant, anti-inflammatory, and antiapoptotic effects, leading to cardioprotective benefits. Nevertheless, the exact intracellular mechanisms of its action are still unclear. In this review, evidence of the potential benefits of hydrogen molecules obtained from in vitro, in vivo, and clinical investigations are comprehensively summarized and discussed with a focus on the cardiovascular aspects. The potential mechanisms involved in the protective effects of molecular hydrogen are also presented. These findings suggest that molecular hydrogen could be used as a novel treatment in various cardiovascular pathologies, including ischemic-reperfusion injury, cardiac injury from radiation, atherosclerosis, chemotherapy-induced cardiotoxicity, and cardiac hypertrophy.

The effect of hydrogen-rich water consumption on premenstrual symptoms and quality of life: a randomized controlled trial.

BACKGROUND: Premenstrual syndrome (PMS) consists of psychiatric or somatic symptoms negatively affecting the daily life. PMS treatment can involve the use of complementary-alternative approaches. Hydrogen-rich water (HRW) has antioxidant and anti-inflammatory properties that may treat PMS. This study aimed to investigate the effect of drinking HRW on the severity of premenstrual symptoms and the quality of life of women who suffer from PMS. METHODS: This study is a randomized controlled trial. Participants were randomized into two groups (intervention group=33, control group=32) using the block randomization method. Participants were requested to consume 1500-2000 mL of HRW daily in the intervention group and drink water in the placebo group. Participants began drinking either HRW or placebo water from day 16 of their menstrual cycle until day 2 of the following cycle for three menstrual cycles. The research data were collected using a Demographic Information Form, Premenstrual Syndrome Scale (PMSS), and Short form of the World Health Organization Quality of Life Questionnaire (WHOQOL- BREF). RESULTS: The intervention group had significantly lower mean scores than the control group in both the first and second follow-ups on the PMSS (P<0.05). In the first follow-up, the intervention group had significantly higher mean scores in the Physical Health and Psychological domains of the WHOQOL-BREF compared to the control group (P<0.05). Group × time interaction was significant for PMSS (F = 10.54, P<0.001). Group × time interaction was insignificant for WHOQOL- BREF (P>0.05). CONCLUSIONS: The consumption of HRW reduces the severity of premenstrual symptoms and improves individuals' quality of life in physical and psychological domains.

Hydrogen-rich solvent method in phytochemical extraction: Potential mechanisms and perspectives.

INTRODUCTION: Phytochemicals are used in many products, including foods, beverages, pharmaceuticals, and cosmetics. The extraction of phytochemicals is considered one of the best solutions to valorize these underestimated materials. Many methods have been developed to efficiently extract phytochemicals at high quality, high purity, and low costs without harming the environment. Recently, molecular hydrogen (H2 ) has shown its ability to improve the extraction of phytochemicals from plant materials. Due to its unique physicochemical and biological properties, H2 showed an efficient ability to extract phenolics and antioxidants at high yields with cost-effective potential. Without sophisticated equipment and high energy and solvent consumption, the hydrogen extraction method is a green and applicable alternative for the extraction of phytochemicals. OBJECTIVES: This review aims to provide the latest knowledge and results concerning the studies on using hydrogen-rich solvents to extract phytochemicals from different agri-food wastes, by-products, and other plant materials. MATERIALS AND METHODS: Recent literature relating to extracting phytochemicals by the hydrogen-rich solvent method and its potential mechanisms is summarized to provide a basic understanding of how hydrogen can improve the extraction of phytochemicals. RESULTS: This review describes, for the first time, the practical procedure of how researchers and laboratories can apply the hydrogen extraction method under safe conditions at a low-budget scale. The review provides some examples of the hydrogen extraction method and the mechanisms and rationale behind its effectiveness. CONCLUSIONS: It can be concluded that the hydrogen-rich solvent method is a green and cost-effective method for extracting phytochemicals from different plant materials.

Hydrogen as an innovative nootropic in health and disease.

Molecular hydrogen (H2, dihydrogen) is an antioxidant and signaling molecule with potent antioxidative, antiapoptotic, and anti-inflammatory properties. Despite the growing interest in H2 as a potential therapeutic agent, the evidence regarding its potential as a nootropic remains limited. Only a handful of studies on the human population have evaluated its effects, although there are suggestive indications of its efficacy. The present paper overviews H2's potential as a novel agent for improving cognitive functions in health and disease contexts, highlighting its mechanisms of action and areas for further investigation. Current evidence suggests that H2 improves executive function, alertness and memory in several clinical trials, from healthy young and elderly individuals to individuals with altered circadian rhythms, neurodegenerative disorders, and cancer. Further investigations are needed to confirm the potential positive effects of dihydrogen as a nootropic agent in both health and disease.

The Protective Role of Molecular Hydrogen in Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) represents a significant contributor to morbidity and mortality associated with various clinical conditions, including acute coronary syndrome, stroke, and organ transplantation. During ischemia, a profound hypoxic insult develops, resulting in cellular dysfunction and tissue damage. Paradoxically, reperfusion can exacerbate this injury through the generation of reactive oxygen species and the induction of inflammatory cascades. The extensive clinical sequelae of IRI necessitate the development of therapeutic strategies to mitigate its deleterious effects. This has become a cornerstone of ongoing research efforts in both basic and translational science. This review examines the use of molecular hydrogen for IRI in different organs and explores the underlying mechanisms of its action. Molecular hydrogen is a selective antioxidant with anti-inflammatory, cytoprotective, and signal-modulatory properties. It has been shown to be effective at mitigating IRI in different models, including heart failure, cerebral stroke, transplantation, and surgical interventions. Hydrogen reduces IRI via different mechanisms, like the suppression of oxidative stress and inflammation, the enhancement of ATP production, decreasing calcium overload, regulating cell death, etc. Further research is still needed to integrate the use of molecular hydrogen into clinical practice.

Comparative Study on Proton Conductivity and Mechanism Analysis of Two Imidazole Modified Imine-Based Covalent Organic Frameworks.

This work elucidates the potential impact of intramolecular H-bonds within the pore walls of covalent organic frameworks (COFs) on proton conductivity. Employing DaTta and TaTta as representative hosts, it was observed that their innate proton conductivities (σ) are both unsatisfactory and σ(DaTta)<σ(TaTta). Intriguingly, the performance of both imidazole-loaded products, Im@DaTta and Im@TaTta is greatly improved, and the σ of Im@DaTta (0.91×10-2  S cm-1 ) even surpasses that of Im@TaTta (3.73×10-3  S cm-1 ) under 100 °C and 98 % relative humidity. The structural analysis, gas adsorption tests, and activation energy calculations forecast the influence of imidazole on the H-bonded system within the framework, leading to observed changes in proton conductivity. It is hypothesized that intramolecular H-bonds within the COF framework impede efficient proton transmission. Nevertheless, the inclusion of an imidazole group disrupts these intramolecular bonds, leading to the formation of an abundance of intermolecular H-bonds within the pore channels, thus contributing to a dramatic increase in proton conductivity. The related calculation of Density Functional Theory (DFT) provides further evidence for this inference.

Molecular hydrogen: prospective treatment strategy of kidney damage after cardiac surgery.

Cardiac surgery-associated acute kidney injury is a common post-operative complication, mostly due to increasing oxidative stress. Recently, molecular hydrogen (H2 gas) has also been applied to cardiac surgery due to its ability to reduce oxidative stress. We evaluated the potential effect of H2 application on the kidney in an in vivo model of simulated heart transplantation. Pigs underwent cardiac surgery within 3 h while connected to extracorporeal circulation (ECC) and subsequent 60 min of spontaneous reperfusion of the heart. We used two experimental groups: T-pigs after transplantation and TH-pigs after transplantation treated with 4% H2 mixed with air during inhalation of anesthesia and throughout oxygenation of blood in ECC. The levels of creatinine, urea and phosphorus were measured in plasma. Renal tissue samples were analyzed by Western blot method for protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1), and superoxide dismutase (SOD1). After cardiac surgery, selected plasma biomarkers were elevated. However, H2 therapy was followed by the normalization of all these parameters. Our results suggest activation of Nrf2/Keap1 pathway as well as increased SOD1 protein expression in the group treated with H2. The administration of H2 had a protective effect on the kidneys of pigs after cardiac surgery, especially in terms of normalization of plasma biomarkers to control levels.

High-Precision Trace Hydrogen Sensing by Multipass Raman Scattering.

Despite its growing importance in the energy generation and storage industry, the detection of hydrogen in trace concentrations remains challenging, as established optical absorption methods are ineffective in probing homonuclear diatomics. Besides indirect detection approaches using, e.g., chemically sensitized microdevices, Raman scattering has shown promise as an alternative direct method of unambiguous hydrogen chemical fingerprinting. We investigated the suitability of feedback-assisted multipass spontaneous Raman scattering for this task and examined the precision with which hydrogen can be sensed at concentrations below 2 parts per million. A limit of detection of 60, 30, and 20 parts per billion was obtained at a pressure of 0.2 MPa in a 10-min-long, 120-min-long, and 720-min-long measurement, respectively, with the lowest concentration probed being 75 parts per billion. Various methods of signal extraction were compared, including asymmetric multi-peak fitting, which allowed the resolution of concentration steps of 50 parts per billion, determining the ambient air hydrogen concentration with an uncertainty level of 20 parts per billion.

The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease.

Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.

APOA2: New Target for Molecular Hydrogen Therapy in Sepsis-Related Lung Injury Based on Proteomic and Genomic Analysis.

Target biomarkers for H2 at both the protein and genome levels are still unclear. In this study, quantitative proteomics acquired from a mouse model were first analyzed. At the same time, functional pathway analysis helped identify functional pathways at the protein level. Then, bioinformatics on mRNA sequencing data were conducted between sepsis and normal mouse models. Differential expressional genes with the closest relationship to disease status and development were identified through module correlation analysis. Then, common biomarkers in proteomics and transcriptomics were extracted as target biomarkers. Through analyzing expression quantitative trait locus (eQTL) and genome-wide association studies (GWAS), colocalization analysis on Apoa2 and sepsis phenotype was conducted by summary-data-based Mendelian randomization (SMR). Then, two-sample and drug-target, syndrome Mendelian randomization (MR) analyses were all conducted using the Twosample R package. For protein level, protein quantitative trait loci (pQTLs) of the target biomarker were also included in MR. Animal experiments helped validate these results. As a result, Apoa2 protein or mRNA was identified as a target biomarker for H2 with a protective, causal relationship with sepsis. HDL and type 2 diabetes were proven to possess causal relationships with sepsis. The agitation and inhibition of Apoa2 were indicated to influence sepsis and related syndromes. In conclusion, we first proposed Apoa2 as a target for H2 treatment.

Molecular Hydrogen Therapy-A Review on Clinical Studies and Outcomes.

With its antioxidant properties, hydrogen gas (H2) has been evaluated in vitro, in animal studies and in human studies for a broad range of therapeutic indications. A simple search of "hydrogen gas" in various medical databases resulted in more than 2000 publications related to hydrogen gas as a potential new drug substance. A parallel search in clinical trial registers also generated many hits, reflecting the diversity in ongoing clinical trials involving hydrogen therapy. This review aims to assess and discuss the current findings about hydrogen therapy in the 81 identified clinical trials and 64 scientific publications on human studies. Positive indications have been found in major disease areas including cardiovascular diseases, cancer, respiratory diseases, central nervous system disorders, infections and many more. The available administration methods, which can pose challenges due to hydrogens' explosive hazards and low solubility, as well as possible future innovative technologies to mitigate these challenges, have been reviewed. Finally, an elaboration to discuss the findings is included with the aim of addressing the following questions: will hydrogen gas be a new drug substance in future clinical practice? If so, what might be the administration form and the clinical indications?

Molecular Hydrogen Reduces the Degree of Endothelial Alteration under Conditions of Chronic Heart Failure.

We studied the effect of molecular hydrogen H2 on the content of circulating endothelial cells and the macrohistological structure of the heart in rats with simulated chronic heart failure. Inhalation with 2% H2 was carried out repeatedly (40 min per day for 5 consecutive days) or once (40 min). Molecular hydrogen inhalations in both regimens caused a decrease in the number of circulating endothelial cells; the most pronounced effect was observed after repeated inhalations on day 14 after chronic heart failure modeling. The decrease in the count of circulating endothelial cells under the action of H2 was accompanied by recovery of the myocardial structure and a decrease in its weight. Molecular hydrogen in chronic heart failure limited the damage to endothelial cells and improved the structure of rat myocardium, which allows us to consider H2 inhalations as the means reducing the progression of chronic heart failure.

A randomized, placebo-controlled clinical trial of hydrogen/oxygen inhalation for non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide with increasing incidence consistent with obesity, type 2 diabetes and cardiovascular diseases. No approved medication was currently available for NAFLD treatment. Molecular hydrogen (H2 ), an anti-oxidative, anti-inflammatory biomedical agent is proved to exhibit therapeutic and preventive effect in various diseases. The purpose of this study was to investigate the effect of hydrogen/oxygen inhalation on NAFLD subjects and explore the mechanism from the perspective of hepatocyte autophagy. We conducted a randomized, placebo-controlled clinical trial of 13-week hydrogen/oxygen inhalation (China Clinical Trial Registry [#ChiCTR-IIR-16009114]) including 43 subjects. We found that inhalation of hydrogen/oxygen improved serum lipid and liver enzymes. Significantly improved liver fat content detected by ultrasound and CT scans after hydrogen/oxygen inhalation was observed in moderate-severe cases. We also performed an animal experiment based on methionine and choline-deficient (MCD) diet-induced mice model to investigate effect of hydrogen on mouse NASH. Hydrogen/oxygen inhalation improved systemic inflammation and liver histology. Promoted autophagy was observed in mice inhaled hydrogen/oxygen and treatment with chloroquine blocked the beneficial effect of hydrogen. Moreover, molecular hydrogen inhibited lipid accumulation in AML-12 cells. Autophagy induced by palmitic acid (PA) incubation was further promoted by 20% hydrogen incubation. Addition of 3-methyladenine (3-MA) partially blocked the inhibitory effect of hydrogen on intracellular lipid accumulation. Collectively, hydrogen/oxygen inhalation alleviated NAFLD in moderate-severe patients. This protective effect of hydrogen was possibly by activating hepatic autophagy.

Molecular hydrogen is a potential protective agent in the management of acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome, which is a more severe form of ALI, are life-threatening clinical syndromes observed in critically ill patients. Treatment methods to alleviate the pathogenesis of ALI have improved to a great extent at present. Although the efficacy of these therapies is limited, their relevance has increased remarkably with the ongoing pandemic caused by the novel coronavirus disease 2019 (COVID-19), which causes severe respiratory distress syndrome. Several studies have demonstrated the preventive and therapeutic effects of molecular hydrogen in the various diseases. The biological effects of molecular hydrogen mainly involve anti-inflammation, antioxidation, and autophagy and cell death modulation. This review focuses on the potential therapeutic effects of molecular hydrogen on ALI and its underlying mechanisms and aims to provide a theoretical basis for the clinical treatment of ALI and COVID-19.

Non-Covalent Interactions in Molecular Systems: Thermodynamic Evaluation of the Hydrogen-Bond Strength in Amino-Ethers and Amino-Alcohols.

The intramolecular hydrogen bond (intra-HB) is one of the best-known examples of non-covalent interactions in molecules. Among the different types of intramolecular hydrogen bonding, the NH⋅⋅⋅O hydrogen bond in amino-alcohols and amino-ethers is one of the weakest. In contrast to the strong OH⋅⋅⋅N intramolecular hydrogen bond, the strength of the NH⋅⋅⋅O bond can hardly be measured with conventional spectroscopic methods, even for simple amino-alcohols, since the band belonging to the NH⋅⋅⋅O conformer merges with the free OH band. In this work, we developed a combination of G4 calculations, and a method based on experimental vaporization enthalpies to determine the NH⋅⋅⋅O hydrogen bonding strength. The archetypal compounds for this study are 2-amino-1-ethanol and 3-amino-1-propanol as well as their respective methoxy analogs. Based on these molecules, different series were studied to investigate various factors influencing NH⋅⋅⋅O intra-HB strength. In the first series, the influence of alkylation near the hydroxy or methoxy group and the amino group in sterically hindered aminoalcohols was examined. In the second series, the influence of alkylation of the amino-group was investigated. In the third series, the effect of extending the alkyl chain between functional groups was studied.

Molecular hydrogen suppresses Porphyromonas gingivalis lipopolysaccharide-induced increases in interleukin-1 alpha and interleukin-6 secretion in human gingival cells.

Periodontitis is defined as a multifactorial polymicrobial infection accompanied by inflammatory reactions. Porphyromonas gingivalis (Pg) is known as a major pathogen in the initiation and progression of periodontitis, and a major virulence factor is Pg lipopolysaccharide (LPS). Molecular hydrogen (H2) has been reported to act as a gaseous antioxidant, which suppresses periodontitis progression by decreasing gingival oxidative stress. However, no human periodontitis model has examined the anti-inflammatory effects of H2. In this study, we examined the effects of H2 on Pg LPS-induced secretion of 8 types of inflammation markers in a human periodontitis model using human gingival cells with enzyme-linked immunosorbent assays. Our results demonstrated that Pg LPS increased interleukin (IL) 1 alpha (IL-1α) and IL-6 secretion, but H2 significantly suppressed the secretion of both cytokines without cytotoxicity. H2 can suppress the production of IL-1α and IL-6, which are identified as cytokines involved in inflammatory reactions in periodontal disease. Thus, H2 may provide therapeutic applications for periodontitis.