Hydrogen Gas Cancer Research Results

H2, Hydrogen Gas: Click to Expand ⟱
Features:
Hydrogen Gas, Powerful Antioxidant
Mechanistically, H₂ is most defensibly framed as a selective antioxidant + anti-inflammatory signaling modulator (often via Nrf2↑ and NF-κB↓ / NLRP3↓), with strongest clinical relevance in oncology being reduction of treatment toxicities (radiation/CCRT side-effects), with mixed/early evidence for direct anticancer effects.

1.Antioxidant and Nrf2/ARE Pathway: activate Nrf2, which induces antioxidant enzymes.
2.NF-κB Pathway: reported to inhibit NF-κB activation, thereby reducing inflammatory cytokine production
3.Mitochondrial Apoptosis Pathway
4.MAPK (Mitogen-Activated Protein Kinases) Pathway
5.PI3K/Akt/mTOR Pathway
6.Inflammatory Cytokine Signaling: Reducing cytokines (such as IL-6, TNF-α)
7.p53 Pathway
8.Autophagy Pathways: might regulate autophagy, (dual roles in cancer)

Example unit sometimes used in studies
Example Canadian Supplier

Hydrogen gas can be generated in small amount by hydrogenase of certain members of the human gastrointestinal tract microbiota from unabsorbed carbohydrates in the intestine through degradation and metabolism, which then is partially diffused into blood flow and released and detected in exhaled breath, indicating its potential to serve as a biomarker.

Many studies have shown that H2 therapy can reduce oxidative stress. This, however, contradicts radiation therapy and chemotherapy, in which ROS are required to induce apoptosis and combat cancer. Yet many studies show chemoprotective and radioprotective and some even show chemosentizing
Nevertheless there are some papers claiming ROS ↑ for cancer cells

Hydrogen Gas in Water is also used.
- the amount of H2 dissolved in solutions is limited: up to 0.8 mM (1.6 mg/L) H2 can be dissolved in water under atmospheric pressure at room temperature


Hydrogen Gas — molecular hydrogen (H₂) is a small, neutral diatomic gas investigated as a therapeutic medical gas and redox-signaling modulator. It rapidly diffuses across biological membranes and can be administered by inhalation or indirectly as hydrogen-rich water (HRW), hydrogen-rich saline, or hydrogen-releasing materials. H₂ is best classified as an experimental therapeutic gas rather than a conventional antioxidant drug. Standard abbreviations are H₂ for molecular hydrogen and HRW for hydrogen-rich water. Endogenous H₂ is also produced by intestinal microbial fermentation. Its biological effects appear to involve modulation of oxidative stress, inflammation, mitochondrial function, cell-death signaling, and immune metabolism rather than indiscriminate ROS scavenging alone.

Primary mechanisms (ranked):

  1. Redox modulation and selective suppression of highly damaging oxidative/nitrosative stress, with secondary NRF2-dependent antioxidant adaptation.
  2. Suppression of inflammatory signaling, particularly NF-κB and associated cytokine pathways.
  3. Mitochondrial and metabolic modulation, including preservation or remodeling of mitochondrial bioenergetics and PGC-1α-linked signaling.
  4. Immune modulation, including reported restoration of metabolically exhausted CD8+ T-cell function in cancer.
  5. Context-dependent regulation of tumor-cell ROS, apoptosis, pyroptosis, differentiation, proliferation, and PI3K/Akt/mTOR signaling.
  6. Protection of normal tissues from chemotherapy- and radiotherapy-associated oxidative and inflammatory injury.

Bioavailability / PK relevance: H₂ has unusually rapid tissue diffusion because of its very small, nonpolar structure, but tissue exposure is transient because hydrogen is rapidly redistributed and exhaled. Inhalation provides continuing systemic exposure during administration, whereas HRW delivers a comparatively small finite H₂ dose that falls rapidly after preparation and ingestion. At approximately atmospheric pressure and room temperature, water saturation is only about 1.6 mg/L H₂, approximately 0.8 mmol/L. Biological efficacy therefore depends strongly on route, concentration, treatment duration, and proximity of H₂ generation to the target tissue.

In-vitro vs systemic exposure relevance: H₂ does not behave like a conventional concentration-maintained small-molecule drug. Gas-equilibrated cell culture can provide sustained H₂ exposure that is difficult to reproduce with a single oral dose of HRW. Conversely, inhalation can continuously replenish dissolved H₂ during treatment. Results from prolonged gas-equilibrated cultures, high-pressure systems, or locally generated H₂ nanomaterials should therefore not automatically be extrapolated to ordinary hydrogen-water exposure.

Clinical evidence status: Small human studies and randomized adjunctive trials exist, but H₂ is not an established anticancer therapy. The most credible oncology application currently is supportive treatment during chemotherapy or radiotherapy. A 2025 randomized study in cervical-cancer patients receiving concurrent chemoradiotherapy reported reduced acute radiation enteritis and inflammatory responses with adjunctive H₂/O₂ inhalation without an apparent reduction in tumor-control efficacy. Direct antitumor evidence remains predominantly preclinical, observational, or derived from small uncontrolled cancer cohorts. Trials of HRW during glioma radiochemotherapy and other indications remain exploratory. H₂ should therefore be classified as experimental adjunct/supportive therapy rather than standalone cancer treatment.

Hydrogen Gas Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Redox and reactive oxygen species regulation ROS ↑ or ↓ (model-dependent) Excess ROS ↓; oxidative damage ↓ P, R Redox modulation H₂ should not be treated as a simple universal ROS scavenger. Normal-tissue studies predominantly show reduced oxidative injury, whereas some tumor models paradoxically show ROS ↑ and ROS-dependent tumor cell death.
2 NRF2 antioxidant stress response NRF2 ↔ or ↑ (context-dependent) NRF2 ↑; HO-1 ↑; SOD ↑; GSH-associated defenses ↑ R, G Adaptive antioxidant signaling NRF2 activation is mechanistically important mainly for cytoprotection and stress adaptation rather than as a consistent direct anticancer mechanism.
3 NF-κB inflammatory signaling NF-κB ↓ (context-dependent) NF-κB ↓; inflammatory injury ↓ R, G Anti-inflammatory signaling Frequently accompanied by IL-6 ↓, TNF-α ↓ and IL-1β ↓. This pathway is particularly relevant to normal-tissue protection during inflammatory injury and cancer therapy.
4 Mitochondrial bioenergetics and PGC-1α Mitochondrial function ↑ in exhausted immune cells; tumor response model-dependent Mitochondrial damage ↓; ATP homeostasis ↑ R, G Bioenergetic remodeling H₂ can improve mitochondrial resilience. In cancer, an important proposed mechanism is metabolic restoration of exhausted antitumor lymphocytes rather than direct mitochondrial poisoning of tumor cells.
5 CD8 T-cell exhaustion and antitumor immunity Indirect tumor suppression ↑ CD8+ T-cell metabolic fitness ↑ G Immune restoration Clinical observations in colorectal and lung cancer suggest restoration of exhausted CD8+ T-cell function, including mitochondrial and CoQ10-associated effects. Evidence remains preliminary.
6 PI3K Akt mTOR proliferative signaling PI3K ↓; p-Akt ↓; mTOR signaling ↓ (model-dependent) ↔ or context-dependent G Growth suppression Reported particularly in experimental colorectal-cancer models. This is not yet established as a reproducible systemic mechanism in patients.
7 NLRP3 caspase-1 GSDMD pyroptosis ROS ↑; NLRP3 ↑; caspase-1 ↑; GSDMD-mediated pyroptosis ↑ (model-dependent) NLRP3 commonly ↓ during inflammatory injury R, G Context-dependent inflammatory cell death An important example of opposite modulation by biological context. H₂ induced ROS-dependent NLRP3-mediated pyroptosis in an endometrial-cancer model, whereas normal-tissue inflammatory models commonly show NLRP3 suppression.
8 Tumor proliferation and differentiation Proliferation ↓; differentiation ↑ (model-dependent) Generally ↔ G Tumor phenotype modulation Glioblastoma models report differentiation of glioma stem-like cells and reduced tumor growth. Generalization to other cancers is uncertain.
9 Angiogenesis and hypoxic signaling HIF-1α ↓; VEGF ↓ (model-dependent) VEGF responses mixed G Angiogenic suppression Preclinical evidence suggests inhibition in selected tumor models but does not establish a general antiangiogenic clinical effect.
10 Glycolytic metabolism HK2 ↓; PFK ↓; glycolysis ↓; lactate production ↓ (model-dependent) ↔ or context-dependent G Metabolic growth restriction Reported in selected experimental cancer systems and should remain secondary until replicated across models.
11 Chemosensitization Therapeutic response ↑ in selected models Chemotherapy-associated organ injury ↓ G Adjunctive treatment modulation H₂ has produced both chemoprotective normal-tissue effects and occasional tumor chemosensitization. Protection of normal tissues should not be interpreted as established protection of tumors.
12 Radiotherapy tissue protection Tumor control apparently ↔ in limited human data Radiation-associated oxidative and inflammatory injury ↓ R, G Supportive radioprotection A randomized cervical-cancer study reported reduced acute radiation enteritis during chemoradiotherapy without evidence of compromised short-term antitumor efficacy. Larger confirmation is required.
13 Clinical Translation Constraint Direct anticancer efficacy unproven Generally well tolerated in studied protocols G Exposure and evidence limitation H₂ exposure varies substantially with inhaled concentration, flow, duration, HRW concentration, storage, and delivery technology. Gas mixtures containing high H₂ concentrations require engineered control because hydrogen is flammable and explosive in air. No standardized oncology dose or approved anticancer indication exists.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr



Hydrogen Gas and Alzheimer’s disease: Molecular hydrogen has substantial preclinical neuroprotective evidence and limited early human evidence in Alzheimer’s disease and mild cognitive impairment. Proposed mechanisms include oxidative-stress suppression, neuroinflammation reduction, mitochondrial protection, BDNF-related signaling, and reductions in Aβ/BACE-associated pathology and tau phosphorylation. H₂ readily diffuses into the CNS, making delivery biologically plausible, but clinical evidence remains insufficient to classify it as a disease-modifying AD treatment.

Clinical evidence status: Preclinical evidence is extensive relative to the small clinical literature. Human studies include an open-label inhalation pilot in AD, a single-arm biomarker study, and a randomized hydrogen-rich-water study in mild cognitive impairment. Reported cognitive or biomarker improvements are hypothesis-generating; adequately powered randomized trials with validated AD endpoints are still needed.

Hydrogen Gas Alzheimer-Relevant Mechanisms

Rank Pathway / Axis Modulation TSF Primary Effect Notes / Interpretation
1 Oxidative and mitochondrial stress ROS ↓; lipid oxidation ↓; mitochondrial damage ↓ P, R Neuroprotection One of the most consistently reproduced effects in experimental neurodegeneration models.
2 Neuroinflammatory signaling NF-κB ↓; IL-1β ↓; IL-6 ↓; TNF-α ↓ R, G Neuroinflammation suppression Likely interconnected with redox and glial responses.
3 NRF2 antioxidant response NRF2 ↑; HO-1 ↑; endogenous antioxidant defenses ↑ R, G Cellular stress resistance Secondary adaptive mechanism rather than simple chemical radical scavenging.
4 Amyloid beta and BACE signaling Aβ ↓; BACE-associated processing ↓ (model-dependent) G Amyloid pathology reduction Demonstrated mainly in experimental models; human disease-modifying evidence is not established.
5 Tau phosphorylation p-tau ↓ (model-dependent) G Tau pathology attenuation Supported primarily by animal and experimental hydrogen-delivery studies.
6 BDNF and neuronal plasticity BDNF ↑; neuronal plasticity ↑ G Cognitive and synaptic support Reported across several neurologic injury models and investigated as a biomarker in human inhalation studies.
7 NLRP3 inflammasome NLRP3 ↓ R, G Microglial inflammatory suppression Potential connection between oxidative stress, innate immune activation, and neurodegeneration.
8 Cognition and memory Memory ↑; cognitive performance ↑ (model-dependent) G Functional outcome Robust in several animal paradigms but human trials remain small and heterogeneous.
9 Clinical Translation Constraint Evidence insufficient for established AD treatment G Clinical evidence limitation Existing human studies are small, often uncontrolled, or use surrogate endpoints. Optimal concentration, inhalation duration, treatment schedule, and long-term efficacy remain unresolved.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr
Scientific Papers found: Click to Expand⟱
4306- H2,    Molecular Hydrogen as an Emerging Candidate for Preventing Alzheimer’s Disease
- Review, AD, NA
*ROS↓, As the result, drinking H2-water reduced oxidative stress in DAL101 mice, suppressed a decline in learning and memory impairment, and suppressed neurodegeneration
*memory↑,
*neuroP↑,
*OS↑, Moreover, H2-water extended the average lifespan of DAL mice [1].
*Inflam↓, Additionally, H2 reduced oxidative stress and inflammation in an amyloid-β-induced Alzheimer rat model [27].

7482- H2,    Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA - Review, Sepsis, NA - Review, AD, NA
Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.

7481- H2,  Rad,    Clinical Efficacy of Hydrogen Therapy on Acute Radiation Enteritis and Inflammatory Response in Patients with Cervical Cancer Undergoing Concurrent Chemoradiation Therapy
- Trial, Var, NA
Dose↝, The experimental group received inhalation therapy with a hydrogen-oxygen gas mixture (66.6% hydrogen, 33.3% oxygen; 3 L/min, 2 h/d) on each radiation therapy day.
CRP↓, experimental group showed significantly lower levels of C-reactive protein, neutrophil-to-lymphocyte ratio, interleukin 6, and fecal occult blood positivity rates
NLR↓,
IL6↓,
AntiTum∅, Importantly, no significant difference in tumor response was observed between groups based on the Response Evaluation Criteria in Solid Tumors
*toxicity↓, Hydrogen inhalation is a safe and effective adjunctive therapy that significantly alleviates inflammation and mitigates clinical symptoms of ARE in patients with cervical cancer who are undergoing CCRT, without compromising antitumor treatment outcom
Inflam↓,
radioP↑,
*IBI↑, significant reduction in fecal occult blood positivity in the hydrogen group (χ² = 16.278, P < .001), reinforcing its protective effect on intestinal mucosa integrity.
*ROS↓, Molecular hydrogen has demonstrated a unique capacity to selectively scavenge cytotoxic ROS

4347- H2,    Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study
- ex-vivo, NA, NA
*AntiAg↑, Collagen-induced platelet aggregation was significantly decreased in H2 gas and HS group rats (p=0.042, 0.018, respectively),

4346- H2,    Medical Application of Hydrogen in Hematological Diseases
- Review, NA, NA
*AntiAg↑, hydrogen-rich saline may inhibit collagen-induced platelet aggregation in healthy volunteers' blood samples.
*TNF-α↓, hydrogen may improve the body weight, number of peripheral blood cells, and the bone marrow microenvironment by decreasing the levels of TNF-α, IFN-γ, and IL-6.
*IL6↓,
*IFN-γ↓,
*NF-kB↓, decreased activation of NF-κB

4345- H2,    The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease
- Human, NA, NA
*Inflam↓, anti-inflammatory and antioxidant effects of hydrogen gas are attributed to its ability to target reactive oxygen species (ROS) and inhibit NLRP3 inflammasome activation in macrophages
*antiOx↑,
*ROS↓,
*NLRP3↑,
*NF-kB↓, inhibiting the activation of the transcription factor NF-κB
*SOD↑, hydrogen gas regulates the expression of antioxidant enzymes like superoxide dismutase (SOD) and catalase, providing protection against oxidative stress-induced damage
*Catalase↑,
*AntiAg↑, Additionally, Qian et al. found that hydrogen-rich saline may inhibit collagen-induced platelet aggregation in healthy volunteers’ blood samples.

4344- H2,    Hydrogen May Inhibit Collagen-Induced Platelet Aggregation: An ex vivo and in vivo Study
- in-vivo, NA, NA - ex-vivo, NA, NA
*AntiAg↑, Collagen-induced platelet aggregation was significantly decreased in H 2 gas and HS group rats (p= 0.042, 0.018, respectively)

4343- H2,    Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation
- vitro+vivo, NA, NA
*antiOx↑, H2 has antithrombotic effects, which may be due to its antioxidant property and subsequent inhibition of platelet activation via NO/cGMP/PKG/ERK pathway.
*AntiAg↑,
*NO↑,
*ERK↑,

4308- H2,    A biomimetic upconversion nanoreactors for near-infrared driven H2 release to inhibit tauopathy in Alzheimer's disease therapy
- in-vivo, AD, NA
*BioAv↝, However, conventional administration methods of H2 face significant challenges in controlling H2 release on demand and fail to achieve effective accumulation at lesion sites.
*ROS↓, As an antioxidant, hydrogen gas (H2) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH.
*p‑tau↓, nanoreactors release H2 in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model.
*Dose↝, Currently, H2 administration can be achieved through three common routes, which include inhalation of H2, oral intake of H2-rich water, and injection of H2-dissolved saline
*cognitive↑, Moreover, such a local H2 generation in the cortex and hippocampus rescued the neuronal density and improved cognitive function by suppressing p-tau pathology in mice of AD models.

4307- H2,    Hydrogen Gas Attenuates Toxic Metabolites and Oxidative Stress-Mediated Signaling to Inhibit Neurodegeneration and Enhance Memory in Alzheimer’s Disease Models
- in-vivo, AD, NA
*cognitive↑, H2 treatment significantly prevented cognitive deficits, oxidative stress, the accumulation of toxic metabolites, and the increase in inflammatory markers in 5xFAD mice.
*Inflam↓,
*ROS↓, H2 therapy has been shown to attenuate OS via selective reduction in ROS. 1.2-fold decrease in ROS levels
*neuroP↑, thereby reducing neurodegeneration and memory loss in AD.
*memory↑,
*BBB↑, making it easy for H2 to penetrate cell membranes and cross the blood–brain barrier
*BDNF↑, H2 therapy has been shown to modulate brain-derived neurotrophic factor and estrogen receptor β,
*TNF-α↓, We observed a significant reduction in TNF-α mRNA levels
*Catalase↑, 1.4-fold increase in catalase activity
*IL6↓, H2 treatment markedly suppressed TNF-α and IL-6 mRNA expression by 1.6-fold
*Aβ↓, observed that Aβ plaque accumulation in GFAP decreased by 2.8-fold in the cortex
*GABA↓, GABA levels were markedly lower
*Dose↝, Approximately 1–4% of H2 is deemed safe [ 36 ], and 3% of inhaled H2 has been reported to improve cognitive and diffusion tensor imaging scores in patients with AD

7483- H2,  Cisplatin,    Molecular hydrogen attenuates cisplatin-induced nephrotoxicity by modulating β-hydroxybutyrate metabolism
- in-vivo, Nor, HK-2
RenoP↑, H2 inhalation significantly attenuated cisplatin-induced kidney injury by reducing inflammation and apoptosis in renal tissue.
BHB↑, H2 upregulated the ketone body metabolic pathway, particularly enhancing β-hydroxybutyrate (β-HOB) synthesis via increased expression of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2).
HMGCS2↑,
chemoP↑, Molecular hydrogen confers protection against cisplatin-induced nephrotoxicity by modulating β-HOB metabolism through upregulation of HMGCS2, thereby suppressing renal inflammation and apoptosis.
*IL2↓, IL-1β, IL-6, MCP-1, and TNF-α in kidney tissue. Levels of these proinflammatory mediators were significantly elevated following cisplatin treatment. H2 inhalation significantly suppressed these cytokines,
*IL6↓,
*MCP1/CCL2↓,
*TNF-α↓,
*KeyT↝, H2 upregulated HMGCS2 to enhance ketone body metabolism
*Inflam↓, H2 has been demonstrated protective effects in various inflammatory and oxidative stress-related conditions
*ROS↓,
*MMP↑, Several studies have shown that H2 can preserve mitochondrial membrane potential, boost ATP generation, and improve mitochondrial dynamics and biogenesis by activating pathways such as mitofusin-2 (Mfn2) and PGC-1α
*ATP↑,
*MFN2↑,
*PGC-1α↑,
*BUN↓, Our work confirmed that H2 inhalation significantly ameliorated cisplatin-induced histological damage, elevated BUN and creatinine levels, renal inflammation, and tubular apoptosis.
*creat↓,

4237- H2,    Hydrogen-Rich Saline Protects Against Spinal Cord Injury in Rats
- in-vitro, NA, NA
*Apoptosis↓, administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions.
*ROS↓,
*motorD↑,
*BDNF↑, Hydrogen-rich saline increased the release of BDNF.

4236- H2,    Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model
- in-vivo, Stroke, NA
*neuroP↑, H2 gas administration exerted a neuroprotective effect against early brain injury after ICH through anti-inflammatory, neuroprotective, anti-apoptotic, and antioxidative activity.
*Inflam↓,
*antiOx↑,
*BDNF↑, neuroprotective benefits of hydrogen inhalation might owe to down-regulation of caspase-3-related apoptotic signaling, and upregulation of BDNF expression related
*Casp3↓,

4235- H2,    PPARα contributes to the therapeutic effect of hydrogen gas against sepsis-associated encephalopathy with the regulation to the CREB-BDNF signaling pathway and hippocampal neuron plasticity-related gene expression
- in-vivo, Sepsis, NA
*PPARα↑, H2 alleviates sepsis-induced brain injury in mice through the regulation of neurotrophins and hippocampal plasticity-related genes via PPARα by activating the CREB-BDNF signaling pathway.
*CREB↑,
*BDNF↑,
*OS↑, activation of PPARα in septic mice improved the survival rate and alleviated cognitive dysfunction.
*cognitive↑,

4234- H2,    Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice
- in-vivo, Sepsis, NA
*cognitive↑, 2% H2 protects against sepsis-induced cognitive impairment in septic mice.
*DNMT1↓, 2% H2 decreases DNMT1, DNMT3a but not DNMT3b levels in the hippocampus.
*DNMT3A↓,
*BDNF↑, 2% H2 enhances BDNF levels through hypomethylating the BDNF promoter IV.

3787- H2,    Hydrogen, a Novel Therapeutic Molecule, Regulates Oxidative Stress, Inflammation, and Apoptosis
- Review, AD, NA
*Inflam↓, anti-inflammatory and antioxidant activity
*antiOx↑,
*ROS↓, annihilating excess reactive oxygen species production and modulating nuclear transcription factor.
*other↝, H2 does not explode if it is <10% when mixed with air or O2
*NF-kB↓, H2-rich saline inhibited the activation of crucial inflammatory signaling pathway NF-κB and reduced serum IL-1β, IL-6, and TNF-α levels,
*IL2↓,
*IL6↓,
*TNF-α↓,
*HO-1↑, Studies have demonstrated that H2 administration increased the HO-1 expression
Apoptosis↑, Similarly, cell apoptosis and autophagy were significantly enhanced in A549 and H1975 lung cancer cell lines treated with different concentrations of H2 gas
TumAuto↑,
*Sepsis↓, sepsis-related organ injury models, H2 treatment significantly reduced the expression of caspase-1 in the damaged organ and the levels of IL-1β and IL-18 cytokines
*NLRP3↓, NLRP3, caspase-1, and the N-terminal of gasdermin D (GSDMD-N), were reduced after lung inflation with 3% H2,
Pyro↑, H2-rich water inhibited the proliferation of endometrial cancer cells by triggering the NLRP3 inflammasome/caspase-1 mediated classical pyroptosis pathway and activated the downstream proinflammatory cytokine IL-1β.

3777- H2,    Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders
- Review, AD, NA - Review, Stroke, NA - Review, Park, NA
*neuroP↑, imary mechanism underlying hydrogen's neuroprotection.

3776- H2,    The role of hydrogen in Alzheimer's disease
- Review, AD, NA
*antiOx↑, hydrogen has shown great anti-oxidative stress and anti-inflammatory effect in many cerebral disease models.
*Inflam↓,
*NLRP3↓, hydrogen could inhibit the activation of NLRP3 inflammasome in AD brains
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a
*SIRT1↑,
*FOXO3↑,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling
*BDNF↑, by reducing the decline in brain estrogen levels, estrogen receptor (ER) β, and the expression of brain-derived neurotrophic factor (BDNF),

3775- H2,    Molecular hydrogen therapy for neurological diseases: a review of current evidence
- Review, AD, NA - Review, Stroke, NA
*Inflam↓, anti-inflammatory and antioxidative effects.
*antiOx↑,
*neuroP↑, demonstrate neuroprotective effects of hydrogen therapy in stroke, neurodegenerative diseases, neurotrauma, and global brain injury.
*cognitive↑, Oral hydrogen water intake ameliorated cognitive impairment in senescent accelerated mice.

2503- H2,    Brain Metastases Completely Disappear in Non-Small Cell Lung Cancer Using Hydrogen Gas Inhalation: A Case Report
- Case Report, Lung, NA
TumVol↓, Hydrogen-gas monotherapy was started to control the tumor a month later. After 4 months, the size of multiple brain tumors was reduced significantly
OS↑, After 1 year, all brain tumors had disappeared, and there were no significant changes in metastases in the liver and lung.
Dose↝, The hydrogen oxygen nebulizer (AMS-H-03, Asclepius Meditec, Shanghai, China) generates 3 L/min hydrogen gas by hydrocephalus electrolysis. As measured by gas chromatography, the gas generated consisted of 67% hydrogen and 33% oxygen.
Dose↝, Using a special mask, the patient continued to inhale hydrogen for 3–6 hrs a day at rest, with no interruption even after the obvious relief of symptoms.
CEA↓, dropped from 29.44 to 12 ng/mL in 12 months (figure 3)
CA125↓, dropped from 150 to 60 u/mL (figure 3)
CYFRA21-1↓, dropped from 12 to 6 ng/mL (figure 3)
SIRT1↓, several scholars have demonstrated that hydrogen can suppress SIRT1 signaling in different model
COX2/PTGS2↓, hydrogen exerts neuroprotective effects by reducing cyclooxygenase-2 activity25 or activating expression of anti-apoptotic protein kinase B.
IL1β↓, Hydrogen inhalation can down-regulate the expression of various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, intracellular adhesion molecule-1, high mobility group box-1, nuclear factor-kappa B, and prosta
IL6↓,
TNF-α↓,
HMGB1↓,
NF-kB↓,
EP2↓, and prostaglandin-E2

7925- H2,    Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice
- in-vivo, Asthma, NA
*Dose?, received inhalation of 67% high concentration of hydrogen gas for 60 min once a day for 7 consecutive days after OVA or PBS challenge respectively
*IL4↓, Increased level of IL-4, IL-13, TNF-α and CXCL15 in the BALF and IL-4 in the serum were decreased significantly after inhalation.
*IL13↓,
*TNF-α↓,
*CXCL15↓,
*SOD↑, Hydrogen gas inhalation markedly upregulated the activity of decreased superoxide dismutase
*MDA↓, and significantly attenuated the increased level of malondialdehyde and myeloperoxidase
*MPO↓,
*ROS↓, Hydrogen gas inhalation improves lung function and protects established airway inflammation in the allergic asthmatic mice model which may be associated with the inhibition of oxidative stress process.
*antiOx↑, therapeutic effects of molecular hydrogen on various diseases have been investigated regarding its antioxidation capability [4] and its anti-inflammation [5] and anti-apoptosis
*Inflam↓,
*Apoptosis↓,
*toxicity↓, it is sufficiently mild that it does not disturb metabolic oxidation-reduction reactions or ROS-mediated cell signalling. Thus, it may be a safe and effective antioxidant for pulmonary diseases
*Stroke↓, , accumulating evidence has demonstrated various types of diseases involving oxidative stress, including ischaemic heart disease [7], stroke [8], acute lung injury [9] and inflammatory bowel disease
*Airway↓, Hydrogen gas inhalation decreased lung resistance in the asthmatic mice model
*Neut↓, There was a significant increase in the number of total cells, neutrophils , eosinophils , lymphocytes . Hydrogen gas inhalation resulted in significant reduction in the number of total cells
*Eos↓,
*BALF-Lym↓,
*BALF-Infl↓, Hydrogen gas inhalation attenuated the elevated levels of inflammatory cytokines present in BALF from the asthmatic mouse model
*AirwayM↓, In our study, we found the hydrogen gas inhalation significantly alleviated the pathologic inflammation degree and mucus content in the lung tissue.

7934- H2,    Hydrogen-generating silicon-based agent is effective in a mouse model of ovalbumin-induced allergic bronchial asthma
- in-vivo, Asthma, NA
*IgE↓, Silicon-based agent tended to decrease the total IgE concentration in serum
*antiOx↑, Hydrogen therapy, which involves the intake of hydrogen as an antioxidant, has been reported to be effective against various oxidative stress-related diseases.
*Eos↓, The administration in the diet of this Si-based agent to a model mouse of allergic bronchial asthma significantly suppressed eosinophil counts in the BALF and reduced inflammatory cell infiltration in the lungs
*BALF-Infl↓,
*IL5↓, the expressions of interleukins 5, and 13 and C–C motif chemokine 11 in lung tissue tended to decreased in the Si group compared with those in the control group
*IL13↓,
*CCL11↓,

7933- H2,    Hydrogen inhalation ameliorates lung inflammation in mice with asthma
- in-vivo, Asthma, NA
*antiOx↑, Hydrogen has been shown to exhibit antioxidant and anti-inflammatory properties that are beneficial for a range of diseases.
*Inflam↓,
*IL4↓, Hydrogen inhalation attenuated the immune response; decreased the levels of IL-4, IL-5 and IL-13;
*IL5↓,
*IL13↓,
*IL10↑, and further increased the mRNA expression levels of Treg-associated cytokines, namely, IL-10 and TGF-β1, thereby bolstering the body's inflammatory resistance mechanisms.
*TGF-β1↑,
*IgE↓, it also reduced total serum IgE levels and malondialdehyde (MDA) production and increased superoxide dismutase (SOD) secretion in lung tissue.
*MDA↓,
*SOD↑,
*Airway↓, Inhalation of hydrogen decreases airway resistance in asthmatic mice

7932- H2,    Hydrogen Gas Inhalation Alleviates Airway Inflammation and Oxidative Stress on Ovalbumin-Induced Asthmatic BALB/c Mouse Model
- in-vivo, Asthma, NA
*antiOx↑, Molecular hydrogen (H2) has recently been recognized for its antioxidant and anti-inflammatory properties
*Inflam↓,
*ROS↓, inhaled H2 significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity.
*TAC↑,
*IgE↓, Furthermore, H2 also significantly decreased serum IgE levels, a marker of allergic inflammation.
*Dose↝, 3% H2 gas inhalation on OVA-induced inflammatory airway conditions, body and lung weights were recorded in mice.
*NLR↓, Our results also demonstrated a significant decline in the NLR in the HT group compared to the NT group
*IL4↓, Conversely, the levels of IL-4 (p < 0.001; Figure 4A), IL-5 (p < 0.001; Figure 4B), IL-13 (p < 0.01; Figure 4C), and GM-CSF (p < 0.01; Figure 4F) were significantly lower in the HT group than in the NC group
*IL5↓,
*IL13↓,
*GM-CSF↓,
*NO↓, NO (p < 0.05; Figure 5B) levels were reduced in the HT group compared with those in the NC group
*GPx↑, treatment with 3% H2 significantly increased the GPx activity in the HT group compared to that in the NC group
*Eos↓, In our study, we observed that H2 inhalation reduced neutrophils in the OVA-induced asthmatic BALB/c mouse model

7931- H2,    Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells
- in-vitro, Asthma, NA
*p‑FcεRI↓, Using rat RBL-2H3 mast cells, we demonstrated that hydrogen attenuates phosphorylation of the FcepsilonRI-associated Lyn and its downstream signal transduction
*NADPH↓, which subsequently inhibits the NADPH oxidase activity and reduces the generation of hydrogen peroxide.
*H2O2↓,
*Dose↝, We found that oral intake of hydrogen-rich water abolishes an immediate-type allergic reaction in mice.

7930- H2,    Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation
- in-vivo, Asthma, NA
*GutMicro↑, The findings revealed that HRW influenced gut microbiota by increasing Ligilactobacillus and Bifidobacterium abundance and enhancing the presence of indole-3-acetic acid (IAA), a microbially derived serum metabolite.
*Inflam↓, In summary, HRW can modify gut microbiota, increase Bifidobacterium abundance, elevate microbial-derived IAA levels, and activate AhR, which could potentially alleviate inflammation in asthma.
*Dose↝, HRW is water with a high concentration of hydrogen gas, typically up to 0.6 mM (1.2 ppm) or higher, generated using high-pressure dissolution, electrolysis of water [19], and hydrogen dissolution by nano-bubbles
*AirwayM↓, Periodic acid-schiff (PAS) staining revealed that HRW significantly reduced mucus secretion a

7929- H2,    Hydrogen-rich saline reduces airway remodeling via inactivation of NF-κB in a murine model of asthma
- NA, Asthma, NA
*IL4↓, The results showed that hydrogen-rich saline reduced cell counts and levels of cytokines IL-4, IL-5, IL-13 and TNF-α in BALF.
*IL5↓,
*IL13↓,
*TNF-α↓,
*AirwayM↓, Hydrogen-rich saline treatment also significantly decreased mucus index, collagen deposition, and expression of MUC5AC, collagen III and VEGF.
*MUC5AC↓,
*COL3A1↓,
*VEGF↓,
*NF-kB↓, The ratio of phospho-NF-κB p65 to total NF-κB p65 was much lower in mice treated with hydrogen-rich saline than in untreated mice.
*Inflam↓, These effects of hydrogen-rich saline on airway inflammation and remodeling were dose-dependent

7928- H2,    Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis
- in-vivo, Asthma, NA
*IL33↓, Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice.
*NF-kB↓, The expression of NF-κB (p65) and ST2 was upregulated by OVA and suppressed by H2.
*IL1RL1/ST2↓,
*ILC2↓, ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2.
*E-cadherin↑, E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment.
*ZO-1↑,
*Inflam↓, These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation.

7927- H2,    Hydrogen gas (XEN) inhalation ameliorates airway inflammation in asthma and COPD patients
- Human, Asthma, NA
*IL8↓, decreased IL-8 level only in asthma group
*IL4↓, IL-4 and IL-6 levels in EBC were significantly lower after inhalation in the COPD (0.80–0.64 pg/mL, P = 0.025) and asthma (0.06–0.05 pg/mL, P = 0.007) group, respectively.
*IL6↓,
*Inflam↓, A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD
*Sepsis↓, has been demonstrated that hydrogen could provide protection against various diseases, including sepsis, stroke and ischemia-reperfusion injury
*Stroke↓,
*antiOx↑, Hydrogen, which exhibits anti-oxidative and anti-inflammation effects, was proved to be relatively safe for inhalation in diving.9
*toxicity↓,

7926- H2,    Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model
- in-vivo, Asthma, NA
*Dose↝, Hydrogen gas was delivered to the mice through inhalation twice a day (2 h once) for 7 consecutive days
*Airway↓, Hydrogen gas inhalation significantly alleviated OVA-induced airway hyperresponsiveness, inflammation and goblet cell hyperplasia, diminished TH2 response and decreased IL-4 as well as IgE levels, reduced malondialdehyde (MDA) production
*BALF-Infl↓,
*Th2↓,
*IL4↓,
*IgE↓,
*MDA↓,
*SOD↑, increased superoxide dismutase (SOD) activity
*NF-kB↓, hydrogen gas inhalation inhibited NF-κB activation and markedly activated Nrf2 pathway in OVA-induced asthmatic mice.
*NRF2↑,

3774- H2,    The role of hydrogen in Alzheimer’s disease
- Review, AD, NA
*Inflam↓, hydrogen inhalation exhibit anti-inflammatory and anti-oxidant effects in many studies.
*antiOx↑,
*NLRP3↓, decline of nucleotide-binding domain leucin-rich repeat and pyrin domain-containing protein 3 (NLRP3) was proved to inhibit memory impairment and Aβ deposition.4
*memory↑,
*Aβ↓,
*AMPK↑, hydrogen-rich water can stimulate AMPK-Sirt1-FoxO3a pathway
*SIRT1↑,
*FOXO3↑,
*p‑p38↓, hydrogen water could suppress the activation of phospho-p38 and JNK
*JNK↓,
*ROS↓, hydrogen can reduce neuronal apoptosis by inhibiting ROS-activated caspase signaling and protecting mitochondria.
*cognitive↑, Currently, Hou et al.50 reported that hydrogen-rich water could improve cognition function in female transgenic AD mice by reducing the decline in brain estrogen levels, estrogen receptor (ER) β
*ER(estro)↑,
*BDNF↑, and the expression of brain-derived neurotrophic factor (BDNF),

7492- H2,  Chemo,    Molecular Hydrogen Protects against Various Tissue Injuries from Side Effects of Anticancer Drugs by Reducing Oxidative Stress and Inflammation
- Review, Var, NA
*ROS↓, reduces reactive oxygen species, which have very strong oxidative capacity, and indirectly exerts antioxidant, anti-inflammatory
*antiOx↑,
*Inflam↓,
*chemoP↑, Our comprehensive literature review revealed that H2 protects against tissue injuries induced by cisplatin, oxaliplatin, doxorubicin, bleomycin, and gefitinib.
AntiCan↑, Animal and clinical studies showed that H2 itself exhibits anticancer activity, and its combination with anticancer drugs achieved excellent anticancer activity
ChemoSen↑,
chemoP↑, Our literature review revealed that H2 reduced the side effects of CIS-induced nephrotoxicity, ototoxicity, and ovarian injury, CIS- or OXA-induced peripheral neuropathy, DXR-induced cardiotoxicity and hepatotoxicity, and BLM- or GEF-induced lung inj
*BUN↓, CIS Nephrotoxicity BUN ↓, Creatinine ↓, TUNEL ↓
*creat↓,
*TUNEL↓,
*MDA↓, CIS Ototoxicity MDA ↓, 8-iso-PGF2α ↓
*SOD↑, CIS Ovarian injury SOD ↑, CAT ↑, MDA ↓, Nrf2 ↑
*Catalase↑,
*NRF2↑,
*BNP↓, DXR Cardiotoxicity and hepatotoxicity BNP ↓, AST ↓, ALT ↓, ROS ↓, MDA ↓, TNF-α ↓, IL-1β ↓, IL-6 ↓, TUNEL ↓, Bax/Bcl-2 ↓, Caspase-3 ↓, Caspase-8 ↓
*AST↓,
*ALAT↓,
*TNF-α↓,
*IL1β↓,
*IL6↓,
*Casp3↓,
*Casp9↓,
*GPx↑, BLM Lung injury ROS ↓, MDA ↓ TGF-β1 ↓,TNF-α ↓, GSH-PX ↑, E-cadherin ↑, Vimentin ↓, α-SMA ↓, Collagen I ↓
*E-cadherin↑,
*Vim↓,
*α-SMA↓,
*COL1↓,
*cardioP↑, H2 ameliorated DXR-induced cardiotoxicity and hepatotoxicity by attenuating inflammation and apoptosis.
*hepatoP↑,
*p‑mTOR↓, decreased the phosphorylated mammalian target of rapamycin (p-mTOR) to mTOR
*EMT↓, H2 gas also inhibited BLM-mediated epithelial-to-mesenchymal transition by increasing the expression level of the epithelial cell marker E-cadherin and decreasing that of the mesenchymal cell marker vimentin [
eff∅, On the other hand, H2 did not impair the anticancer effects of GEF in in vitro experiments on lung cancer cell lines or in in vivo experiments on carcinoma-bearing mice
*LPS↓, figure 2
*TLR4↓,
radioP↑, radioprotective effects of H2 have also been reported in many in vitro and in vivo studies, and clinical trials recently showed that the inhalation of H2 gas mitigated decreases in quality of life and bone marrow damage associated with radiation [

7491- H2,    Transdermal hydrogen therapy for psoriasis using cavity-embedded double-conical microneedles
- in-vivo, PSA, NA
*Dose↝, designed a double-conical microneedle with high loading capacity and effective skin penetration to efficiently deliver MgH2 powders, enabling the sustained release of molecular hydrogen within the skin tissue.
*ROS↓, The transdermal hydrogen therapy greatly relieved oxidative damages, pro-inflammatory cytokine expression, immune cell infiltration, and ultimately mitigated keratinocyte hyperproliferation and systemic symptoms.

7490- H2,    Long-term administration of hydrogen-rich water enhances quality of life in diabetic rats and reduces renal neoplasm incidence through modulation of inflammatory and metabolic pathways
- in-vivo, Diabetic, NA
*BG↓, Long-term administration of HRW significantly decreased FBG levels and increased BW, indicating an improvement in metabolic control.
*AntiDiabetic↑,
*BMD↑, HRW also ameliorated various DM-related complications, including diabetic cataracts, bone loss, diabetic nephropathy, erectile dysfunction, asthenozoospermia, and renal neoplasms.
*hepatoP↑, revealed significant enrichment of metabolic pathway-related genes in testis, liver, kidney, and stomach tissues, suggesting the reprogramming of metabolic functions.
*RenoP↑,
*QoL↑, The findings suggest that oral ingestion of HRW is a safe, effective, and convenient treatment that improves quality of life for DM patients by reducing blood glucose levels and alleviating diabetic complications.

7489- H2,    Molecular Hydrogen in the Treatment of Respiratory Diseases
- Review, Asthma, NA
*antiOx↑, Molecular hydrogen is gaining increasing attention as an antioxidant, anti-inflammatory, and antiapoptotic agent.
*Inflam↓,
*Apoptosis↓,
*Dose↓, It reaches a maximum level of about 0.78 mM (≈1.6 mg/L) at room temperature with a loss of about 2–5% per 3 min
*Dose↝, It is produced (and consumed) by bacteria of the gut microbiota .The most prominent bacterial phyla involved in this process are the Firmicutes and Bacteroidetes phyla, which include the anaerobic Clostridium species
*eff↑, hydrogen mixed with oxygen at a ratio of 96%-to-4%, known as the Hydrox gas mixture, was used by deep-sea divers to prevent decompression sickness and allow diving to depths of up to 500 m
*ROS↓, The antioxidant activity of H2 is based on two processes: a direct scavenging of the most toxic reactive oxygen and nitrogen species (ROS/RNS),
*RNS↓,
*NRF2↑, H2 activates the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway, a key transcription factor involved in oxidative stress-related responses, including cytoprotective, antioxidant, and detoxifying enzymes such as HO-1
*HO-1↑,
*Fenton↓, removal of free heme and inhibition of the Fenton reaction
*NLRP3↓, the activation of the Nrf2 pathway has been shown to inhibit the NLRP3 (NLR family pyrin domain containing 3) inflammasome,
*NADPH↓, H2 suppresses the activation of the NADPH oxidase pathway and downregulates the expression of NOX2 and NOX4
*NOX4↓,
*NOX↓,
*MPO↓, H2 has been shown to reduce the overactivation of myeloperoxidase (MPO)
*NF-kB↓, would further suppress the NFκB
*TNF-α↓, figure 3
*IL6↓,
*IL1β↓,
*HMGB1↓,
*IL4↑,
*IL10↑,
*M2 MC↑, Additionally, H2 promotes the polarization of macrophages from the proinflammatory M1 type to the anti-inflammatory M2 type
*Treg lymp↝, It also inhibits Th2 responses, restores regulatory T cells (Treg), and, thus, normalizes an overactivated immune system
*Bcl-2↑, upregulate the antiapoptotic factors, including Bcl-2 and Bcl-xl.
*Bcl-xL↑,
*PI3K↑, phenomenon is likely facilitated by the activation of the PI3K/Akt and JAK2/STAT3 signaling pathways
*Akt↑,
*JAK2↑,
*STAT3↑,
*Dose↑, The consumption of certain prebiotics, especially those rich in dietary fiber, indigestible starches, and sugars (lactulose), has been demonstrated to enhance intestinal H2 production through the activity of intestinal flora
*CD4+↑, H2 increased the population of CD4+CD25+Foxp3+ Treg cells, which are often decreased in allergic rhinitis (AR)
*CD25+↑,
*FOXP3↑,
*MDA↓, H2 administration attenuated oxidative stress expressed as lower MDA and other lipid peroxidation markers along with an enhancement in the expression and activity of endogenous antioxidant enzymes such as SOD or CAT
*SOD↑,
*Catalase↑,
*Casp3↓, inhibition of proapoptotic processes like the caspase 3 and 9 pathways
*Casp9↓,
*TBARS↓, drinking of HRW by patients with asthma and COPD leads to an increase in blood oxygen saturation, vitamin E levels, along with lower oxidative stress markers such as thiobarbituric acid reactive substances (TBARS), MDA,
*SpO2↑,
*VitE↓,
*OS↑, COPD:In general, H2 administration has been found to lead to enhanced survival and reduced weight loss [110], improved lung function and static lung compliance, and decreased arterial blood pressure
*Weight↑,
*DNAdam↓, reduction in levels of oxidative DNA damage markers
*PGE2↓, H2 reduced elevated inflammatory markers, including IL-1β, IL-6, TNF-α, prostaglandin E2 (PGE2) [29,65,71,128,130], macrophage protein 1α 2 (MP1α), and monocyte chemoattractant protein-1 (MCP-1)
*MCP1/CCL2↓,
*lipid-P↓, Further, a reduction in oxidative stress markers such as lipid peroxidation and proapoptotic markers, including Bax and caspase-3, was observed.
*TumCP↓, H2-rich medium reduced the colony size and formation of tongue cancer cells and decreased proliferation in human fibrosarcoma and esophageal cancer cells, as well as A549 cells
*tumCV↓, decrease in cell viability, migration, and invasion
*TumCMig↓,
*TumCI↓,
TumW↓, A reduction in tumor weight and size, as well as a lower number of cells of squamous cell carcinoma, was revealed by animal studies.
TumVol↓,
selectivity↑, Notably, as previously reported, H2 administration exhibited no effect on healthy animals or non-cancerous cell lines
QoL↑, Patients reported improved quality of life with better physical status and fewer pulmonary symptoms
ChemoSen↑, In combination with conventional (such as cis-platin) and modern (including antibodies like nivolumab) therapeutics, H2 enhanced drug activity, resulting in enhanced outcomes and improved disease control
chemoP↑, and reduced side effects of the treatment, such as nephrotoxicity, weight loss, insomnia, pain, or hearing loss in the case of radiotherapy
radioP↑, radioprotective effects of H2 are primarily attributed to its hydroxyl radical scavenging activity
ROS↑, As indicated by Yang et al., the latter include the activation of the ROS/NLRP3/caspase-3/gasdermin D-mediated pyroptotic pathways
NLRP3↑,
Casp3↑,
VEGF↓, suppression of vascular endothelial growth factor (VEGF) expression
Wnt↓, H2 result in the suppression of the overactivated Wnt/beta-catenin signaling pathways, which further leads to suppression of tumor progression
β-catenin/ZEB1↓,

7488- H2,    Molecular hydrogen therapy: A "democratic" emerging strategy against aging and age-related diseases
- Review, Nor, NA
*antiOx↑, antioxidant and anti-inflammatory properties
*Inflam↑,
*toxicity↓, the lack of toxicities and low costs
*AntiAge↑, emerging strategy against aging and age-related diseases

7487- H2,    A comprehensive review of molecular hydrogen as a novel nutrition therapy in relieving oxidative stress and diseases: Mechanisms and perspectives
- Review, Nor, NA
*Inflam↓, H2 demonstrates numerous biologically therapeutic properties, including anti-inflammatory, antioxidant, anti-cancer, anti-stress, anti-apoptotic, anti-allergic effects, signaling molecule functions, regulation of redox balance
*antiOx↓,
*Stress↓,
*Dose↝, The administration methods of hydrogen include inhalation, hydrogen-rich water, hydrogen-rich saline, hydrogen-rich eye drops, and hydrogen-rich bathing.
*cardioP↑, graphical abstract and figure 4
*GastroP↑,
*BBB↑, H2 is its ability to easily cross the blood-brain barrier and penetrate biomembranes, diffusing throughout the different tissues and organs.
*eff↑, The above-cited properties led some researchers to refer to it as a "miracle" molecule
*toxicity↓, Regarding the biosafety of hydrogen, numerous reports, including those from the US government and the EU, have indicated that hydrogen is safe for biological systems, showing no acute or chronic toxicity under normal pressure
*Dose↝, human large intestine often produces approximately 70–140 mL of hydrogen daily through the action of coliform bacteria such as Escherichia coli under typical environmental conditions.
*hepatoP↑, including cardioprotective properties, improved liver function, reduced oxidative stress, and prevention of Parkinson's disease
*ROS↓,
*SOD↑, 1.5–2.0 L/day drinking HRW orally 0.55–0.65 mM 1.65–2.6 mg H2/day 8 weeks SOD: ↑ TRABS: ↓ HDL: ↑
*TBARS↓,
*HDL↑,
*LDL↓, figure 4
*Obesity↓, figure 5 obesity
*GSH↑, HRW treatment partially alleviated colitis symptoms, improved histopathological changes, significantly increased glutathione (GSH) concentration, and reduced the level of TNF-α.
*TNF-α↓,
*GutMicro↑, HRW was found to exhibit partial relief of inflammation, oxidative stress, and dysbiosis in the intestinal flora of mice with chronic ulcerative colitis (UC) induced by dextran sulfate sodium (DSS)
*DNAdam↓, HRW-treated mice exhibited decreased levels of markers associated with oxidative DNA damage, such as phosphorylated histone H2AX and 8-hydroxy-2′-deoxyguanosine, as well as markers indicative of aging
*γH2AX↓,
*p‑p38↓, Treatment with HRS also inhibited the activation of p-p38 and NF-κB while suppressing the production of several pro-inflammatory mediators,
*NF-kB↓,

7486- H2,    Effects of hydrogen-rich water on blood uric acid in patients with hyperuricemia: A randomized placebo-controlled trial
- Trial, Nor, NA
*eff↑, The high-dose of HRW was more effective than low-dose HRW in controlling blood uric acid.
*uricA↓, significant reduction in blood uric acid levels compared to the baseline (488.2 ± 54.1 μmol/L to 446.8 ± 57.1 μmol/L, P < 0.05).
*toxicity↓, As a rather safe agent, the prolonged consumption of HRW may be feasible in the management of hyperuricemia.
*antiOx↑, Molecular hydrogen (H2) has been proven to be an anti-oxidative and anti-inflammatory agen
*Inflam↓,
*Dose↝, various routes for H2 administration such as H2-rich water (HRW) drinking, H2 gas inhalation, and H2 water bath [21,22]. HRW refers to regular water that contains dissolved H2, and HRW drinking is convenient and extremely bio-safe.
*Dose↝, The High-HRW group consumed three bottles of HRW daily.330 mL per bottle. one bottle of water within 10 min in the morning, noon, and evening, respectively.
*Dose↝, H2 concentration was ≥4.66 mg/L. By calculation, the daily H2 intake doses were about 3.08 mg and 4.61 mg in the Low-HRW group and High-HRW group, respectively.
*toxicity↓, H2 is acknowledged as a relatively safe agent. In the food industry, H2 has obtained official approval as a food additive due to its non-toxic properties
*Dose↓, The solubility of H2 in water is approximately 1.6 mg/L under standard conditions (20 °C, 101.325 kPa). The utilization of micro and nanobubbles technologies has been shown to enhance the solubility of H2 in water.
*ROS↓, The mechanisms of HRW consumption on regulating oxidative stress and inflammatory responses, and thereby reducing blood uric acid levels require further inquiry.

7485- H2,    Molecular hydrogen inhibits neuroinflammation and ameliorates depressive-like behaviors and short-term cognitive impairment in senescence-accelerated mouse prone 8 mice
- in-vivo, Nor, NA
*Dose↑, SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26-28 weeks.
*cognitive↑, HRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice.
*memory↑,

7484- H2,    Hydrogen Gas Attenuates Toxic Metabolites and Oxidative Stress-Mediated Signaling to Inhibit Neurodegeneration and Enhance Memory in Alzheimer's Disease Models
- in-vivo, AD, NA
*Dose↝, either 3% hydrogen gas (H2) or vehicle for 60 days.
*cognitive↑, H2 treatment significantly prevented cognitive deficits, oxidative stress, the accumulation of toxic metabolites, and the increase in inflammatory markers in 5xFAD mice.
*ROS↓, H2 treatment significantly attenuated ROS production in AβO-stimulated primary mouse astrocytes, showing a 1.2-fold reduction compared with vehicle
*Inflam↓, H2 Reduced OS and Decreased Neuroinflammation in AβO-Treated Astrocytes
*neuroP↑, H2 therapy can mitigate toxic metabolites in the astrocytic urea cycle, thereby reducing neurodegeneration and memory loss in AD.
*memory↑, H2 Inhalation Attenuates Memory Impairment in 5xFAD Mice
*Catalase↑, catalase activity increased by 20% following H2 treatment, although this increase was insignificant
*TNF-α↓, observed a significant reduction in TNF-α mRNA levels
*Aβ↓, Aβ plaque accumulation in GFAP decreased by 2.8-fold in the cortex
*GABA↓, GABA levels were markedly lower (p < 0.001) in the AβO-induced astrocytes treated with H2 than in those treated with vehicle
*H2O2↓, H2 treatment attenuated toxic metabolite accumulation, including Aβ, H2O2, and GABA, which were markedly reduced after H2
*GFAP↓, These suggest that astrocyte function was enhanced after H2 treatment due to reduced astrogliosis, denoted by the decrease in the GFAP level.
*antiOx↑, The antioxidant defense system is key to H2’s efficacy, which is modulated upstream by nuclear factor erythroid 2-related factor 2 (Nrf2)
*NRF2↑,

2513- H2,    Hydrogen therapy: from mechanism to cerebral diseases
- Review, Stroke, NA
*BBB?, blood-brain barrier, penetrability
*antiOx↑, therefore concluded that this selective antioxidant effect is the basis of H2 therapy for cerebral ischemia/reperfusion injury
*Inflam↓, H2 can decrease both the amount of inflammatory cytokines and immunocyte stimulation
*Apoptosis↓, Research showed that the apoptosis of neurons in newborn rats induced by hypoxia and ischemia is inhibited if inhaling H2,
*NF-kB↓, demonstrated the inhibition of NF-κB with the introduction of H2
*Dose↝, Furthermore, there are many methods for ingestion of H2, such as oral intake of H2 water, intravenous drip of H2 -rich saline, and inhalation of air containing 2–4% H2 gas

3773- H2,    Role and mechanism of molecular hydrogen in the treatment of Parkinson’s diseases
- Review, Park, NA
*neuroP↑, potential neuroprotective effects, attributed to its selective antioxidant and anti-inflammatory properties.
*antiOx↑,
*Inflam↓,
*ROS↓, potential of molecular hydrogen to attenuate oxidative stress,
*NADPH↓, via the inhibition of NADPH oxidase activity
*NRF2↑, it also enhances the endogenous defense system by modulating the Nrf2/ARE pathway.
*BBB↑, easily penetrate the blood–brain barrier
*IL1β↓, H₂ significantly reduces the release of pro-inflammatory factors, including IL-1β, IL-6, TNF-α, NF-κB, and HMGB1,
*IL6↓,
*TNF-α↓,
*NF-kB↓,
*NLRP3↓, hydrogen can mitigate neuroinflammation by inhibiting the NLRP3 inflammasome pathway
*Sepsis↓, hydrogen intervention in sepsis models
*p‑mTOR↓, inhibits the phosphorylation level of mTOR (indicated by a decrease in the p-mTOR/mTOR ratio) while activating the AMPK s
*AMPK↑,
*SIRT1↑, hydrogen-rich water alleviates intestinal oxidative stress by upregulating the expression of SIRT1, Nrf2, and HO-1
*HO-1↑,

2522- H2,    A Systematic Review of Molecular Hydrogen Therapy in Cancer Management
- Review, Var, NA
chemoP↑, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction.
OS↑,
QoL↑,
TumVol↑,
ROS↑, Hydrogen, the lightest element on the earth, is an effective antioxidant that has been shown to selectively reduce harmful reactive oxygen species (ROS) in tissues
AntiTum↑, Although H2 has demonstrated significant anti-tumoural effects, the underlying mechanisms have not yet been elucidated.
other↝, Many studies have shown that H2 therapy can reduce oxidative stress. This, however, contradicts radiation therapy and chemotherapy, in which ROS are required to induce apoptosis and combat cancer.

2521- H2,    Oxyhydrogen Gas: A Promising Therapeutic Approach for Lung, Breast and Colorectal Cancer
- Review, CRC, NA - Review, Lung, NA - Review, BC, NA
Inflam↑, Oxyhydrogen gas, a mixture of 66% molecular hydrogen (H2) and 33% molecular oxygen (O2) has shown exceptional promise as a novel therapeutic agent due to its ability to modulate oxidative stress, inflammation, and apoptosis.
ROS↓, neutralises reactive oxygen and nitrogen species
ChemoSen↑, enhancing existing treatments and reducing harmful oxidative states in cancer cells. boosting the effectiveness of conventional therapies
p‑PI3K↓, inhibiting the PI3K/Akt phosphorylation cascade.
p‑Akt↓,
QoL↑, Similar results have been observed in breast cancer, where patients reported improved quality of life.
GutMicro↑, improves intestinal microflora dysbiosis.
chemoP↑, reduced oxidative stress and mitigated tissue damage, suggesting its potential as a cytoprotective agent in cancer patients undergoing radiation therapy or chemotherapy
radioP↑,
*NRF2↑, documented role in activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
*Catalase↑, consequently, hydrogen can enhance the expression of endogenous antioxidant enzymes, including catalase (CAT), glutathione peroxidase (GPx), haem oxygenase (e.g., HO-1), and superoxide dismutase (SOD) [45]
*GPx↑,
*HO-1↑,
*SOD↑,
*TNF-α↓, reducing the expression of proinflammatory mediators such as chemokines (e.g., CXCL15), cytokines (e.g., TNF-α), interleukins (e.g., IL-4, IL-6)
*IL4↓,
*IL6↓,
ChemoSen↑, further research demonstrates that oxyhydrogen gas enhanced the sensitivity of lung cancer cells to chemotherapy drugs, suggesting its potential as an adjuvant therapy
Appetite↑, inhaled oxyhydrogen gas over a minimum of 3 months. The results indicated substantial improvements in appetite, cognition, fatigue, pain, and sleeplessness
cognitive↑,
Pain↓,
Sleep↑,
other?, It is recommended that hydrogen should not exceed 4.6% in air or 4.1% by volume in pure oxygen gas (explosion risk)

2520- H2,    The Impact of Molecular Hydrogen on Mitochondrial ROS and Apoptosis in Colorectal Cancer Cells
- in-vitro, CRC, NA
mt-ROS↓, hydrogen-rich medium, we found a significant mitochondrial ROS decrease (∼40%), especially in the aldolase B over-expressed CRC
ChemoSen↑, hydrogen can synergize the apoptotic response of chemotherapy (∼20% improvement).
other↝, However, the decreasing mtROS signal and increasing apoptosis seems to be controversial with our current understanding, and further study in more detail is required to explore the underlying mechanisms of mitochondrial function and related signaling

2519- H2,    Hydrogen: an advanced and safest gas option for cancer treatment
- Review, Var, NA
antiOx↑, H2 has remarkable antioxidant and neuroprotective effects and other advantages
neuroP↓,
BBB↑, swift penetration ability to cross the blood–brain barrier
toxicity∅, H2 inhalation therapy has also been proposed in several countries as the safest mode of H2 administration
TumCP↓, A HeLa xenograft mouse model showed that H2 inhalation may increase the apoptosis rate, proliferation, and oxidative stress in HeLa cells
Apoptosis↓,
ROS↑,
Hif1a↓, H2 may affect tumor growth by regulating the expression of overexpressed subunits of transcription factors, such as hypoxia-inducible factor 1α and the nuclear factor-κB p65 subunit
NF-kB↓,
P53?, Hydrogen also increases the expression level of p53 tumor suppressor proteins.
OS↑, This study revealed that hydrogen gas inhalation 3 h/d can improve the prognosis and overall survival of stage IV colorectal carcinoma patients by decreasing the number of programmed cell death 1/CD8+ T cells
chemoP↑, H 2 anticancer therapy can minimize the debilitating side effects of conventional anticancer therapies by improving survival, quality of life, and blood parameters.

2518- H2,    Hydrogen Therapy Reverses Cancer-Associated Fibroblasts Phenotypes and Remodels Stromal Microenvironment to Stimulate Systematic Anti-Tumor Immunity
- in-vitro, BC, 4T1 - in-vitro, Nor, 3T3
TumCD↑, CaCO3 can not only directly kill tumor cells
CD4+↑, augment immune activities of CD4+ T cells
ROS↓, results indicated that hydrogen therapy by Mg-CaCO3 could decrease MMP and alleviate ROS within CAFs

2517- H2,    Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response
- in-vitro, Var, A549 - in-vitro, NA, HCT116 - in-vitro, NA, HeLa - in-vitro, NA, HepG2 - in-vitro, NA, HT1080 - in-vitro, NA, PC3 - in-vitro, NA, SH-SY5Y
TumCP↓, the proliferation of four cell lines (A549, HeLa, HT1080, and PC3 cells) was increased 1.16–1.27-fold by 5% hydrogen gas, and 1.30–1.41-fold by 10% hydrogen
other↝, responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders.
eff↝, Effects of Hydrogen on Cell Proliferation Are Independent of Concentrations of Cellular Reactive Oxygen Species (ROS)
mt-UPR↑, hydrogen induces mtUPR as evidenced by upregulation of mtUPR-related molecules (ATF5, p-eIf2α, and HSP60) in the responders

2516- H2,    Hydrogen Gas in Cancer Treatment
- Review, Var, NA
*Half-Life↓, Except the thigh muscle required a longer time to saturate, the other organs need 5–10 min to reach Cmax (maximum hydrogen concentration).
*ROS↓, regulate several key players in cancer, including ROS, and certain antioxidant enzymes
*selectivity↑, hydrogen gas could selectively scavenge the most cytotoxic ROS, •OH, as tested in an acute rat model of cerebral ischemia and reperfusion
*SOD↑, the expression of superoxide dismutase (SOD) (48), heme oxyganase-1 (HO-1) (49), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) (50), increased significantly, strengthening its potential in eliminating ROS.
*HO-1↑,
*NRF2↑,
*chemoP↑, reduce the adverse effects in cancer treatment while at the same time doesn't abrogate the cytotoxicity of other therapy, such as radiotherapy and chemotherapy
*radioP↑,
ROS↑, Interestingly, due the over-produced ROS in cancer cells (38), the administration of hydrogen gas may lower the ROS level at the beginning, but it provokes much more ROS production as a result of compensation effect, leading to the killing of cancer
*Inflam↓, By regulating inflammation, hydrogen gas can prevent tumor formation, progression, as well as reduce the side effects caused by chemotherapy/radiotherapy
eff↑, More importantly, hydrogen-rich water didn't impair the overall anti-tumor effects of gefitinib both in vitro and in vivo, while in contrast, it antagonized the weight loss induced by gefitinib and naphthalene, and enhanced the overall survival rate
*TNF-α↓, hydrogen-rich saline treatment exerted its protective effects via inhibiting the inflammatory TNF-α/IL-6 pathway, increasing the cleaved C8 expression and Bcl-2/Bax ratio, and attenuating cell apoptosis in both heart and liver tissue
*IL6↓,
*cl‑Casp8↑,
*Bax:Bcl2↓,
*Apoptosis↓,
*cardioP↑,
*hepatoP↑,
*RenoP↑, Hydrogen-rich water also showed renal protective effect against cisplatin-induced nephrotoxicity in rats.
*chemoP↑, nother study showed that both inhaling hydrogen gas (1% hydrogen in air) and drinking hydrogen-rich water (0.8 mM hydrogen in water) could reverse the mortality, and body-weight loss caused by cisplatin via its anti-oxidant property
eff↝, More importantly, hydrogen didn't impair the anti-tumor activity of cisplatin against cancer cell lines in vitro and in tumor-bearing mice
chemoP↑, hydrogen-rich water combinational treatment group exhibited no differences in liver function during the treatment, probably due to its antioxidant activity, indicating it a promising protective agent to alleviate the mFOLFOX6-related liver injury
radioP↑, consumption of hydrogen-rich water reduced the radiation-induced oxidative stress while at the same time didn't compromise anti-tumor effect of radiotherapy
eff↑, Hydrogen Gas Acts Synergistically With Thermal Therapy
TumCG↓, in vivo study showed that under hydrogen gas treatment, tumor growth was significantly inhibited, as well as the expression of Ki-67, VEGF and SMC3
Ki-67↓,
VEGF↓,
selectivity↑, H2-silica could concentration-dependently inhibit the cell viability of human esophageal squamous cell carcinoma (KYSE-70) cells, while it need higher dose to suppress normal human esophageal epithelial cells (HEEpiCs), indicating its selective profi

2515- H2,    Recent Advances in Studies of Molecular Hydrogen against Sepsis
- Review, Sepsis, NA
*Sepsis↓, Molecular hydrogen exerts multiple biological effects involving anti-inflammation, anti-oxidation, anti-apoptosis, anti-shock, and autophagy regulation, which may attenuate the organ and barrier damage caused by sepsis.
*Inflam↓,
*antiOx↑,
*ROS↓, Studies have demonstrated that HRS reduces ROS production and attenuates mitochondrial dysfunction by inhibiting NADPH oxidase activity in rat cardiomyocytes
*NADPH↓,


Showing Research Papers: 1 to 50 of 82
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 82

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

BHB↑, 1,   CD47↓, 1,   HMGCS2↑, 1,   miR-124-3p↓, 1,   NLR↓, 1,   PFS↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   ROS↓, 2,   ROS↑, 4,   mt-ROS↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

PGC-1α↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

SCD1↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 2,   Casp3↑, 1,   IAP2/BIRC3↓, 1,   Pyro↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

EZH2↓, 1,   other?, 1,   other↝, 3,  

Protein Folding & ER Stress(tgid=8) ⓘ

mt-UPR↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

P53?, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK4↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EP2↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

CEA↓, 1,   Ki-67↓, 1,   MALAT1↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

Hif1a↓, 2,   VEGF↓, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 1,   COX2/PTGS2↓, 1,   CRP↓, 1,   HMGB1↓, 1,   IL1β↓, 1,   IL6↓, 2,   Inflam↓, 1,   Inflam↑, 1,   NF-kB↓, 2,   NK cell↑, 1,   TNF-α↓, 1,  

Protein Aggregation(tgid=19) ⓘ

NLRP3↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 6,   Dose↝, 5,   eff↑, 4,   eff↝, 2,   eff∅, 1,   selectivity↑, 3,  

Clinical Biomarkers(tgid=22) ⓘ

CA125↓, 1,   CEA↓, 1,   CRP↓, 1,   CYFRA21-1↓, 1,   EZH2↓, 1,   GutMicro↑, 1,   IL6↓, 2,   Ki-67↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   AntiTum↑, 1,   AntiTum∅, 1,   Appetite↑, 1,   chemoP↑, 8,   cognitive↑, 1,   neuroP↓, 1,   NP/CIPN↓, 1,   OS↑, 3,   Pain↓, 1,   QoL↑, 4,   radioP↑, 6,   RenoP↑, 1,   Sleep↑, 1,   toxicity∅, 1,   TumVol↓, 3,   TumVol↑, 1,   TumW↓, 1,  

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,  
Total Targets: 90

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

Airway↓, 3,   AirwayM↓, 3,   BALF-Infl↓, 3,   BALF-Lym↓, 1,   CCL11↓, 1,   compII↑, 1,   CXCL15↓, 1,   Eos↓, 3,   p‑FcεRI↓, 1,   GFAP↓, 1,   IgE↓, 4,   IL13↓, 5,   IL1RL1/ST2↓, 1,   ILC2↓, 1,   MUC5AC↓, 1,   NLR↓, 1,   SpO2↑, 1,   Stress↓, 1,   Stroke↓, 3,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1,   antiOx↑, 21,   Catalase↑, 7,   Fenton↓, 1,   GPx↑, 4,   GSH↑, 1,   H2O2↓, 2,   HDL↑, 1,   HO-1↑, 6,   lipid-P↓, 1,   MDA↓, 6,   MFN2↑, 1,   MPO↓, 3,   NOX4↓, 1,   NRF2↑, 8,   RNS↓, 1,   ROS↓, 22,   SOD↑, 10,   TAC↑, 1,   TBARS↓, 2,   uricA↓, 1,   VitE↓, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 2,   compIII↑, 1,   MMP↑, 2,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 2,   AMPK↑, 3,   BUN↓, 2,   CREB↑, 1,   KeyT↝, 1,   LDL↓, 2,   NADPH↓, 4,   PPARα↑, 1,   SIRT1↑, 3,  

Cell Death(tgid=5) ⓘ

Akt↑, 2,   Apoptosis↓, 5,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Bcl-xL↑, 1,   Casp12↓, 1,   Casp3↓, 3,   cl‑Casp8↑, 1,   Casp9↓, 2,   GranB/GZMB↓, 1,   JNK↓, 1,   p‑JNK↓, 1,   p38↓, 1,   p‑p38↓, 2,   TUNEL↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,   other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 1,   p‑eIF2α↓, 1,   ER Stress↓, 1,   GRP78/BiP↓, 1,   XBP-1↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

LC3‑Ⅱ/LC3‑Ⅰ↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 2,   DNMT1↓, 1,   DNMT3A↓, 1,   γH2AX↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EMT↓, 1,   ERK↑, 1,   FOXO3↑, 2,   mTOR↓, 1,   p‑mTOR↓, 2,   PI3K↑, 2,   STAT3↑, 1,  

Migration(tgid=13) ⓘ

AntiAg↑, 5,   APP↓, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↑, 2,   TGF-β↑, 1,   TGF-β1↑, 1,   Treg lymp↝, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   Vim↓, 1,   ZO-1↑, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

ATF4↓, 1,   NO↓, 1,   NO↑, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB?, 1,   BBB↑, 3,   GastroP↑, 1,   IBI↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD25+↑, 1,   CD4+↑, 2,   FOXP3↑, 1,   GM-CSF↓, 1,   HMGB1↓, 1,   IFN-γ↓, 2,   IL10↑, 3,   IL1β↓, 4,   IL2↓, 2,   IL33↓, 1,   IL4↓, 8,   IL4↑, 1,   IL5↓, 4,   IL6↓, 11,   IL8↓, 1,   Imm↑, 1,   Inflam↓, 26,   Inflam↑, 1,   JAK2↑, 1,   LPS↓, 2,   M2 MC↑, 1,   MCP1/CCL2↓, 2,   Neut↓, 1,   NF-kB↓, 10,   PGE2↓, 1,   Th2↓, 1,   TLR4↓, 1,   TNF-α↓, 14,  

Cellular Microenvironment(tgid=17) ⓘ

NOX↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

BDNF↑, 7,   GABA↓, 2,   p‑tau↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 4,   BACE/β-secretase↓, 1,   NLRP3↓, 6,   NLRP3↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

BNP↓, 1,   ER(estro)↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↝, 2,   Dose?, 1,   Dose↓, 2,   Dose↑, 2,   Dose↝, 17,   eff↑, 4,   Half-Life↓, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 2,   AST↓, 2,   BG↓, 1,   BMD↑, 1,   creat↓, 3,   GutMicro↑, 3,   IL6↓, 11,   Urea↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1,   AntiDiabetic↑, 1,   antiPs↑, 1,   cardioP↑, 4,   chemoP↑, 3,   cognitive↑, 9,   hepatoP↑, 6,   memory↑, 5,   motorD↑, 1,   neuroP↑, 9,   Obesity↓, 2,   OS↑, 3,   QoL↑, 1,   radioP↑, 1,   RenoP↑, 3,   toxicity↓, 7,   Weight↑, 1,  

Infection & Microbiome(tgid=24) ⓘ

Sepsis↓, 5,  
Total Targets: 183

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:295  Target#:%  State#:%  Dir#:%
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