• Hydrogen
• nano platinum-hydrogen saline
• oxygen-induced retinopathy
• retinopathy of prematurity
• therapy

• Animals
• Retinopathy of Prematurity/chemically induced
• Retinopathy of Prematurity/drug therapy
• Retinopathy of Prematurity/pathology
• Retinopathy of Prematurity/metabolism
• Animals, Newborn
• Rats
• Platinum/administration & dosage
• Platinum/pharmacology
• Platinum/therapeutic use
• Vascular Endothelial Growth Factor A/metabolism
• Oxygen/adverse effects
• Hydrogen/administration & dosage
• Rats, Sprague-Dawley
• Disease Models, Animal
• Oxidative Stress/drug effects
• Metal Nanoparticles
• Saline Solution
• Apoptosis/drug effects
• Malondialdehyde/metabolism
• Reactive Oxygen Species/metabolism

• Apoptosis
• Cisplatin
• IGF1
• Outer hair cell protection
• Oxidative stress

• Animals
• Cisplatin/toxicity
• Insulin-Like Growth Factor I/pharmacology
• Insulin-Like Growth Factor I/metabolism
• Hair Cells, Auditory, Outer/drug effects
• Hair Cells, Auditory, Outer/metabolism
• Hair Cells, Auditory, Outer/pathology
• Apoptosis/drug effects
• Receptor, IGF Type 1/metabolism
• Receptor, IGF Type 1/antagonists & inhibitors
• Ototoxicity
• Oxidative Stress/drug effects
• Antineoplastic Agents/toxicity
• Mice
• Signal Transduction/drug effects
• Mice, Inbred C57BL
• Animals, Newborn
• Organ Culture Techniques
• Insulin-Like Peptides

• Oxidative stress
• ROS-scavenging biomaterials
• Reactive oxygen species (ROS)
• Sensorineural hearing loss

• Humans
• Reactive Oxygen Species/metabolism
• Biocompatible Materials/chemistry
• Animals
• Hearing Loss, Sensorineural/drug therapy
• Hearing Loss, Sensorineural/therapy
• Oxidative Stress/drug effects
• Antioxidants/therapeutic use
• Antioxidants/pharmacology

• antioxidants
• cisplatin
• cisplatin-induced hearing loss (CIHL)
• hearing loss
• ototoxicity
• oxidative stress

• 2022-Iif-004-DOSSENA Research and Innovation Fund of Paracelsus Medical University (PMU-RIF)
• FIZ RM&NT Talent Pool Senior Researcher 042023 Research and Innovation Fund of Paracelsus Medical University (PMU-RIF)

• concurrent chemoradiotherapy
• head and neck cancer
• hydrogen gas

• by Helix Japan Co., Ltd

• anticancer drug
• antitumor drug
• clinical application
• inflammation
• molecular hydrogen
• oxidative stress
• reactive oxygen species
• side effect
• tissue injury

• mesenchymal stem cells
• molecular hydrogen
• regenerative medicine
• stem cell priming
• tissue regeneration

• Cancer treatment
• Hydrogen
• Intestinal flora
• Oxidative stress
• Tumor immunity

• Humans
• Reactive Oxygen Species
• Hydrogen/pharmacology
• Hydrogen/therapeutic use
• Cell Proliferation
• Gastrointestinal Microbiome
• Immunomodulation
• Neoplasms/drug therapy
• Neoplasms/prevention & control

• antioxidant
• clinical trials
• human studies
• hydrogen therapy
• medical gas
• molecular hydrogen

• Animals
• Humans
• Hydrogen/therapeutic use
• Antioxidants/pharmacology
• Antioxidants/therapeutic use

• 313954 The Research Council of Norway

• biological techniques
• biotechnology
• health care

• Rats
• Animals
• Cisplatin/pharmacology
• Kidney/metabolism
• Oxidative Stress
• Pleurotus/metabolism
• Antioxidants/pharmacology
• Antioxidants/metabolism
• Antineoplastic Agents/pharmacology

• Egyptian Atomic Energy Authority

• free radical
• hearing loss
• hydrogen
• inner ear
• sudden deafness

To evaluate the clinical efficacy and safety of hydrogen inhalation in improving hearing loss in patients with long-term survival of nasopharyngeal carcinoma after radiotherapy.

The eustachian tube dysfunction score, pure tone air conduction threshold, bone conduction threshold, the score of tympanogram and otoscope were prospectively observed in patients with deafness after radiotherapy only or combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Paired t test and one-way analysis of variance were used to analyze the data before and after treatment.

A total of 17 patients were observed. The median time from radiotherapy to now was 228 months, and the median time from the diagnose of deafness to now was 92 months. After 4 weeks of hydrogen inhalation, the score of eustachian tube dysfunction, air conduction and bone conduction hearing thresholds were significantly reduced, P values were 0.0293, 0.0027, 0.0404, respectively. The mean air-bone gap, the score of otoendoscopy and tympanogram were also decreased, but the differences were not significant (P = 0.2079, P = 0.0536, P = 0.1056). Patients with radiotherapy alone and concurrent chemo-radiotherapy had significantly lower air conduction hearing threshold after hydrogen absorption (P = 0.0142, P = 0.0495). The results of air and bone hearing thresholds before, 4 and 12 weeks after hydrogen inhalation showed a descending trend. The air and bone hearing thresholds before hydrogen inhalation were 74.69 ± 27.03 dB and 45.70 ± 21.58 dB, respectively. At the 12th week, the mean values of air and bone hearing thresholds were the lowest, which were 66.88 ± 20.88 dB and 40.94 ± 18.93 dB, respectively, but there was no significant difference in air and bone hearing thresholds among all groups (P = 0.6755, P = 0.7712). After hydrogen inhalation treatment, no adverse reactions such as nosebleed, chest pain, dyspnea, nausea, vomiting, dizziness, earache and allergic reaction were observed.

This is the first prospective study on the effect of hydrogen inhalation on hearing improvement in patients with deafness after radiotherapy/chemotherapy for nasopharyngeal carcinoma, suggesting that continuous hydrogen inhalation may be an alternative rehabilitation therapy for these patients.

• In vivo
• LCMS
• Metabolomics
• NIHL
• Noise-induced hearing loss
• Perilymph

• Animals
• Chromatography, High Pressure Liquid
• Cochlea/chemistry
• Cochlea/drug effects
• Cochlea/metabolism
• Gases/pharmacology
• Guinea Pigs
• Hydrogen/pharmacology
• Mass Spectrometry
• Metabolomics/methods
• Noise
• Perilymph/chemistry
• Perilymph/drug effects
• Perilymph/metabolism
• Quality Control
• Software

• AFA Försäkring
• Stiftelsen Tysta Skolan
• Akademiska Sjukhuset
• Uppsala Universitet

• Case report
• Hydrogen gas
• Metastatic gallbladder cancer

Noise exposure or ototoxic drugs instigate various types of damage to the cochlea, resulting in hearing loss (HL). While the incidence of HL is growing continuously, there are, so far, no adequate drugs to prevent or treat HL. Avenanthramide (AVN), a natural product extracted from oats, has been reported to possess anti-oxidant/inflammatory properties, and protect several types of cells. In this study, we investigated whether AVN-C can protect auditory hair cells, and preserve hearing from noise trauma and ototoxic drugs. Wild-type C57BL/6 mice were used to generate several HL models. Serum and perilymphatic fluid samples were analyzed using mass spectrophotometry to detect AVN-C. AVN-C crossed the blood-labyrinth barrier, and was detected in the perilymph after systemic injection. Pretreatment by AVN-C 24 h before exposure to temporary threshold shift noise contributed to the preserving hearing. Moreover, in the case of permanent threshold shift, AVN-C provided significant protection from noise. AVN-C also strongly protected against deterioration in hearing due to kanamycin and furosemide (K + F). According to the results of our scanning electron microscopy analysis, many outer hair cells (OHCs) were destroyed by noise trauma, while AVN-C prevented these losses. OHC loss due to K + F was even more severe, even affecting the apex. Strikingly, AVN-C treatment maintained OHCs at a level comparable to normal cochlea. AVN-C reduced the dichlorofluorescin (DCF)-positive population in gentamicin-treated HEI-OC1 in vitro. The expressions of TNF-a, BAK, IL-1b, and Bcl-2 were attenuated by AVN-C, revealing its antioxidant effects. The results of this study show that AVN-C crosses the blood-labyrinth barrier and provide a significant protection against noise- and drug-induced ototoxicity. Hence, AVN-C is a good candidate for future therapy aimed at protecting against sensorineural HL.

• Cell death in the nervous system
• Drug development

Although the cochlear vascular supply (stria vascularis) is designed to block to certain compounds and molecules, it must enable gas exchange to survive. The inner ear capillaries must deliver oxygen and remove carbon dioxide for the cochlea to function. These gases diffuse through tissues across a concentration gradient to reach the desired target. Tight junctions or the endothelial basement membrane do not impede them. Therefore, gases that can diffuse into the inner ear are attractive as therapeutic agents. The two gases most often used in this way are oxygen and hydrogen, although carbon dioxide, ozone, and argon have also been investigated. Typically, oxygen is delivered as hyperbaric oxygen (HBO) (oxygen at pressure higher than atmospheric) to provide increased oxygen levels to the inner ear. This not only relieves hypoxia, but also has anti-inflammatory and other biochemical effects. HBO is used clinically to treat idiopathic sudden sensorineural hearing loss, and both animal and human studies suggest it may also assist recovery after acute acoustic trauma. Laboratory studies suggest hydrogen works as a free radical scavenger and reduces the strong oxidants hydroxyl radicals and peroxynitrite. It also has anti-apoptotic effects. Because of its anti-oxidant and anti-inflammatory effects, it has been studied as a treatment for ototoxicity and shows benefit in an animal model of cisplatinum toxicity. Gas diffusion offers an effective way to provide therapy to the inner ear, particularly since some gases (oxygen, hydrogen, carbon dioxide, ozone, argon) have important therapeutic effects for minimizing cochlear damage.

• cochlea
• hydrogen
• hyperbaric
• inner ear
• oxygen

• ROS
• Hsp47
• NOX4
• antioxidant
• hearing loss
• transgenic mouse model

Hydrogen is the most abundant chemical element in the universe, and has been used as an inert gas for a long time. More recent studies have shown that molecular hydrogen as a kind of antioxidant, anti-inflammatory, anti-apoptosis, gene expression and signal modulation molecule, can be used for the treatment of many diseases. This review mainly focuses on the research progresses of hydrogen in various medical fields and the possible action mechanisms.

• action mechanisms
• antioxidant
• future direction
• gene expression
• hydrogen
• injection methods
• research progresses
• signal-transduction

• Anti-oxidative effect
• Hydrogen-rich water
• Mongolian gerbil
• Prevention of hearing loss
• Transient cochlear ischemia

• gaseous signal modulator
• molecular hydrogen
• preventive and therapeutic applications
• selective anti-oxidation

Hyperbaric oxygen (HBO) therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA) is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS), breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H₂) can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H₂ on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H₂ on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H₂ at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H₂ promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O₂^•-, H₂O₂, or NO• in PC12 cells during HBO therapy. These results indicated that H₂ effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H₂ could be potentially used as an antioxidant during HBO therapy.

• Animals
• Cell Survival/drug effects
• Hydrogen/pharmacology
• Hydroxyl Radical/metabolism
• L-Lactate Dehydrogenase/metabolism
• Lipid Peroxidation/drug effects
• Oxygen/toxicity
• PC12 Cells
• Rats
• Reactive Oxygen Species/metabolism

• Ginsenoside Rg1
• Nrf2
• cisplatin
• liver injury
• oxidative stress

• Cisplatin
• Keratinocytes
• Oxidative stress
• Reactive oxygen species
• Vitamin D
• Vitamin D analogues

• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Calcitriol/analogs & derivatives
• Calcitriol/pharmacology
• Cell Division/drug effects
• Cell Line
• Cell Proliferation/drug effects
• Cisplatin/pharmacology
• Humans
• Hydrogen Peroxide/pharmacology
• Keratinocytes/drug effects
• Keratinocytes/metabolism
• Membrane Potential, Mitochondrial/drug effects
• Reactive Oxygen Species/metabolism
• Vitamin D/analogs & derivatives
• Vitamin D/pharmacology

• R01 AR056666 NIAMS NIH HHS
• R21 AR066505 NIAMS NIH HHS

Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4 % is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.

• Inflammatory diseases
• Ischemia-reperfusion injury
• Molecular hydrogen