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Soldatov V, Venediktov A, Belykh A, Piavchenko G, Naimzada MD, Ogneva N, Kartashkina N, Bushueva O. Chaperones vs. oxidative stress in the pathobiology of ischemic stroke. Front Mol Neurosci 2024; 17:1513084. [PMID: 39723236 PMCID: PMC11668803 DOI: 10.3389/fnmol.2024.1513084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024] Open
Abstract
As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in the Liebig's barrel of cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting the quality of the proteome in healthy and stressful conditions. This machinery, namely chaperones, assists in folding, refolding, and the utilization of client proteins. The functions of chaperones are especially important for brain cells, which are highly sophisticated in terms of structural and functional organization. Molecular chaperones are known to exert beneficial effects in many brain diseases including one of the most threatening and widespread brain pathologies, ischemic stroke. However, whether and how they exert the antioxidant defense in stroke remains unclear. Herein, we discuss the chaperones shown to fight oxidative stress and the mechanisms of their antioxidant action. In ischemic stroke, during intense production of free radicals, molecular chaperones preserve the proteome by interacting with oxidized proteins, regulating imbalanced mitochondrial function, and directly fighting oxidative stress. For instance, cells recruit Hsp60 and Hsp70 to provide proper folding of newly synthesized proteins-these factors are required for early ischemic response and to refold damaged polypeptides. Additionally, Hsp70 upregulates some dedicated antioxidant pathways such as FOXO3 signaling. Small HSPs decrease oxidative stress via attenuation of mitochondrial function through their involvement in the regulation of Nrf- (Hsp22), Akt and Hippo (Hsp27) signaling pathways as well as mitophagy (Hsp27, Hsp22). A similar function has also been proposed for the Sigma-1 receptor, contributing to the regulation of mitochondrial function. Some chaperones can prevent excessive formation of reactive oxygen species whereas Hsp90 is suggested to be responsible for pro-oxidant effects in ischemic stroke. Finally, heat-resistant obscure proteins (Hero) are able to shield client proteins, thus preventing their possible over oxidation.
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Affiliation(s)
- Vladislav Soldatov
- Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia
| | - Artem Venediktov
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Andrei Belykh
- Pathophysiology Department, Kursk State Medical University, Kursk, Russia
- Research Institute of General Pathology, Kursk State Medical University, Kursk, Russia
| | - Gennadii Piavchenko
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Mukhammad David Naimzada
- Research Institute of Experimental Medicine, Kursk State Medical University, Kursk, Russia
- Laboratory of Public Health Indicators Analysis and Health Digitalization, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
| | - Nastasya Ogneva
- Scientific Center of Biomedical Technologies, Federal Medical and Biological Agency of Russia, Moscow, Russia
| | - Natalia Kartashkina
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Olga Bushueva
- Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russia
- Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia
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Chitapanarux I, Onchan W, Chakrabandhu S, Muangwong P, Autsavapromporn N, Ariyanon T, Akagi J, Mizoo A. Pilot Feasibility and Safety Study of Hydrogen Gas Inhalation in Locally Advanced Head and Neck Cancer Patients. Onco Targets Ther 2024; 17:863-870. [PMID: 39493677 PMCID: PMC11531231 DOI: 10.2147/ott.s478613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 10/24/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose Hydrogen (H2) gas inhalation might alleviate acute radiotherapy toxicities by scavenging free radicals produced by ionizing radiation and anti-inflammatory properties. This study aimed to investigate the feasibility and safety of H2 gas inhalation during concurrent chemoradiotherapy (CCRT) in patients with locally advanced head and neck cancer (LAHNC). Patients and Methods We designed a pilot prospective study combining CCRT with aerosol inhalation of H2 gas. Each patient was scheduled to receive daily intensity-modulated radiotherapy (IMRT) in 33 fractions on a weekday and six cycles of weekly chemotherapy. All patients inhaled H2 gas through a cannula or mask 1 hour per day, 1-2 hours before IMRT. The primary endpoint was the feasibility of H2 inhalation. Eighty percent of the patients who completed at least 20 applications of H2 gas inhalation were considered feasible. The secondary endpoints were safety profiles during H2 gas inhalation (vital signs and symptoms related to H2 gas inhalation) and acute toxicities during CCRT. Results We enrolled 10 patients with LAHNC between July 2023 and December 2023. All patients received 33 fractions of H2 gas inhalation on the same day as the IMRT. Vital signs during and at the end of H2 gas inhalation were stable in all patients. None of the 10 patients had hypertension or hypotension during any of the 33 inhalations. No adverse events related to H2 gas inhalation, such as cough, nasal bleeding, dizziness, headache, nausea, or vomiting, were reported. Grade 3 leukopenia was found in two patients (20%) during the 5th week of CCRT. Grade 2 radiation dermatitis and pharyngitis were found in three patients (30%). Conclusion H2 gas inhalation combined with CCRT is feasible and safe for patients with LAHNC.
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Affiliation(s)
- Imjai Chitapanarux
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Wimrak Onchan
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Somvilai Chakrabandhu
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Pooriwat Muangwong
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Narongchai Autsavapromporn
- Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Tapanut Ariyanon
- Division of Head and Neck Surgery and Oncology and Hyperbaric Oxygen Therapy, Department of Otolaryngology, Chiang Mai University, Chiang Mai, Thailand
| | - Junji Akagi
- Kumamoto Immunity Integrative Medical Clinic, Kumamoto, Japan
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Nag DS, Swain A, Sahu S, Sen B, Vatsala, Parween S. Stroke: Evolution of newer treatment modalities for acute ischemic stroke. World J Clin Cases 2024; 12:6137-6147. [PMID: 39371560 PMCID: PMC11362888 DOI: 10.12998/wjcc.v12.i28.6137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 06/08/2024] [Accepted: 07/03/2024] [Indexed: 08/13/2024] Open
Abstract
Acute ischemic stroke is one of the leading causes of morbidity and mortality worldwide. Restoration of cerebral blood flow to affected ischemic areas has been the cornerstone of therapy for patients for eligible patients as early diagnosis and treatment have shown improved outcomes. However, there has been a paradigm shift in the management approach over the last decade, and with the emphasis currently directed toward including newer modalities such as neuroprotection, stem cell treatment, magnetic stimulation, anti-apoptotic drugs, delayed recanalization, and utilization of artificial intelligence for early diagnosis and suggesting algorithm-based management protocols.
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Affiliation(s)
- Deb Sanjay Nag
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, India
| | - Amlan Swain
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Seelora Sahu
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Biswajit Sen
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, India
| | - Vatsala
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, India
| | - Sadiya Parween
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, India
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Xiao K, Liu J, Sun Y, Chen S, Ma J, Cao M, Yang Y, Pan Z, Li P, Du Z. Anti-inflammatory and antioxidant activity of high concentrations of hydrogen in the lung diseases: a systematic review and meta-analysis. Front Immunol 2024; 15:1444958. [PMID: 39211045 PMCID: PMC11357939 DOI: 10.3389/fimmu.2024.1444958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.
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Affiliation(s)
- Kang Xiao
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
| | - Jianwei Liu
- Public Health Monitoring and Evaluation Institute of Shandong Provincial Center for Disease Control and Prevention, Ji’nan, Shandong, China
| | - Yuxin Sun
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Shangya Chen
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Jiazi Ma
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Mao Cao
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Yong Yang
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Zhifeng Pan
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Peng Li
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
| | - Zhongjun Du
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji’nan, Shandong, China
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Li Q, Shi M, Ang Y, Yu P, Wan B, Lin B, Chen W, Yue Z, Shi Y, Liu F, Wang H, Duan M, Long Y, Bao H. Hydrogen ameliorates endotoxin-induced acute lung injury through AMPK-mediated bidirectional regulation of Caspase3. Mol Immunol 2024; 168:64-74. [PMID: 38428216 DOI: 10.1016/j.molimm.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 04/28/2023] [Accepted: 02/01/2024] [Indexed: 03/03/2024]
Abstract
Septic lung injury is characterized by uncontrollable inflammatory infiltrations and acute onset bilateral hypoxemia. Evidence has emerged of the beneficial effect of hydrogen in acute lung injury (ALI), but the underlying mechanism is unclear. In this research, the recovery action of hydrogen on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells was investigated. The 7-day survival rate and body weight of mice were measured after intraperitoneal injection of LPS. Lung function was determined by a whole body plethysmography (WBP) system using the indicators respiratory rate and enhanced pause. Hematoxylin and eosin (HE) staining confirmed the signs of pulmonary edema and inflammatory ooze. Reverse transcription-polymerase chain reaction (RT-PCR) quantification was used to detect the expression of inflammatory factors. Western blotting analysis evaluated the expression levels of involved proteins in the AMP-activated protein kinase (AMPK) pathway. The experimental results confirmed that hydrogen provided an essential solution to the dissipative effects of LPS on survival rate, weight loss and lung function. The LPS-stimulated inflammatory factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also suppressed by hydrogen in A549 cells. Western blot analysis showed that hydrogen significantly upregulated the levels of phosphorylated AMPK (p-AMPK) and lowered the LPS-induced increased expression of dynamin-related protein 1 (Drp1) and Caspase3. These findings prove that hydrogen attenuated LPS-treated ALI by activating the AMPK pathway, supporting the feasibility of hydrogen treatment for sepsis.
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Affiliation(s)
- Qian Li
- Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Jiangsu 210000, China; Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China
| | - Min Shi
- Department of Anesthesiology, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China
| | - Yang Ang
- Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China
| | - Pan Yu
- Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China
| | - Bing Wan
- Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China
| | - Bin Lin
- Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China
| | - Wei Chen
- Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China
| | - Zichuan Yue
- Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China
| | - Yadan Shi
- Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China
| | - Faqi Liu
- Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China
| | - Hao Wang
- Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China
| | - Manlin Duan
- Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China; Department of Anesthesiology, BenQ Medical Center, the Affiliated BenQ Hospital of Nanjing Medical University, Jiangsu 210019, China.
| | - Yun Long
- Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China.
| | - Hongguang Bao
- Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Jiangsu 210000, China.
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Peng Z, Li XJ, Zhou Y, Zhang JT, Zhu Q, Sun JQ, Hang CH, Li W, Zhang QR, Zhuang Z. Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation. Free Radic Biol Med 2024; 215:79-93. [PMID: 38447853 DOI: 10.1016/j.freeradbiomed.2024.02.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/01/2024] [Accepted: 02/29/2024] [Indexed: 03/08/2024]
Abstract
OBJECTIVE Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.
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Affiliation(s)
- Zheng Peng
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Xiao-Jian Li
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Yan Zhou
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Jia-Tong Zhang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Qi Zhu
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Jia-Qing Sun
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Chun-Hua Hang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China
| | - Wei Li
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China.
| | - Qing-Rong Zhang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China.
| | - Zong Zhuang
- Department of Neurosurgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; Neurosurgical Institute, Nanjing University, Nanjing, China.
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Li J, Huang G, Wang J, Wang S, Yu Y. Hydrogen Regulates Ulcerative Colitis by Affecting the Intestinal Redox Environment. J Inflamm Res 2024; 17:933-945. [PMID: 38370464 PMCID: PMC10871146 DOI: 10.2147/jir.s445152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 01/23/2024] [Indexed: 02/20/2024] Open
Abstract
The redox balance in the intestine plays an important role in maintaining intestinal homeostasis, and it is closely related to the intestinal mucosal barrier, intestinal inflammation, and the gut microbiota. Current research on the treatment of ulcerative colitis has focused on immune disorders, excessive inflammation, and oxidative stress. However, an imbalance in intestinal redox reaction plays a particularly critical role. Hydrogen is produced by some anaerobic bacteria via hydrogenases in the intestine. Increasing evidence suggests that hydrogen, as an inert gas, is crucial for immunity, inflammation, and oxidative stress and plays a protective role in ulcerative colitis. Hydrogen maintains the redox state balance in the intestine in ulcerative colitis and reduces damage to intestinal epithelial cells by exerting its selective antioxidant ability. Hydrogen also regulates the intestinal flora, reduces the harmful effects of bacteria on the intestinal epithelial barrier, promotes the restoration of normal anaerobic bacteria in the intestines, and ultimately improves the integrity of the intestinal epithelial barrier. The present review focuses on the therapeutic mechanisms of hydrogen-targeting ulcerative colitis.
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Affiliation(s)
- Jiayi Li
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Gang Huang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Juexin Wang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Sui Wang
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| | - Yanbo Yu
- Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China
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Zhang Y, Fan W, Li X, Wang WX, Liu S. Enhanced Removal of Free Radicals by Aqueous Hydrogen Nanobubbles and Their Role in Oxidative Stress. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2022; 56:15096-15107. [PMID: 36099323 DOI: 10.1021/acs.est.2c03707] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Elevated levels of reactive oxygen radicals caused by environmental stress are the key triggers of inflammation, aging, and disease; thus, it is critical to develop novel reactive oxygen radical scavenging methods with high efficiency and low toxicity. As a result of their selective reactive oxygen radical removal, hydrogen molecules are strong candidates, but their application is limited by the small hydrogen supply and short duration of action. In this study, we for the first time combined nanobubble (NB) technology and hydrogen water to remove reactive oxygen species (ROS) using copper ions as a representative environmental pollutant and Tetrahymena thermophila as a model organism. Hydrogen NBs displayed a remarkable capability of removing H2O2 and O2•- at molar ratios of 8:1 and 240:1, respectively, which were unable to be removed by dissolved hydrogen molecules only. During the oxidative defense phase, hydrogen NB water either directly removed ROS or increased the activity and relative expression of glutathione peroxidase (GSH-Px). During the oxidative inhibition phase, hydrogen NB water exerted antioxidant effects mainly by increasing the activities of superoxide dismutase and GSH-Px as well as the expression of the corresponding genes. Our results provide an important theoretical support for the wide application of hydrogen NBs in empowering the antioxidant defense system.
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Affiliation(s)
- You Zhang
- Department of Environmental Science and Engineering, School of Space and Environment, Beihang University, Beijing 100191, China
| | - Wenhong Fan
- Department of Environmental Science and Engineering, School of Space and Environment, Beihang University, Beijing 100191, China
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100191, China
| | - Xiaomin Li
- Department of Environmental Science and Engineering, School of Space and Environment, Beihang University, Beijing 100191, China
| | - Wen-Xiong Wang
- School of Energy and Environment and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon, Hong Kong
| | - Shu Liu
- Department of Environmental Science and Engineering, School of Space and Environment, Beihang University, Beijing 100191, China
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Adzavon YM, Xie F, Yi Y, Jiang X, Zhang X, He J, Zhao P, Liu M, Ma S, Ma X. Long-term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways. Sci Rep 2022; 12:3904. [PMID: 35273249 PMCID: PMC8913832 DOI: 10.1038/s41598-022-07710-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 02/22/2022] [Indexed: 11/10/2022] Open
Abstract
Molecular hydrogen (H2) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H2 remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and daily use of H2 on liver function. Rats exposed 2 h daily to H2 either by drinking HRW (H2 dissolved in H2O) or by breathing 4% H2 gas showed reduced lipogenesis and enhanced lipolysis in the liver, which was associated with apparent loss of visceral fat and brown adipose tissue together with a reduced level of serum lipids. Both transcripts and metabolites enriched in H2-treated rats revealed alteration of amino acid metabolism pathways and activation of purine nucleotides and carbohydrate biosynthesis pathways. Analysis of the interaction network of genes and metabolites and correlation tests revealed that NADP is the central regulator of H2 induced metabolic alterations in the liver, which was further confirmed by an increase in the level of components of metabolic pathways that require NADP as substrate. Evidence of immune response regulation activity was also observed in response to exposure to H2. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism.
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Affiliation(s)
- Yao Mawulikplimi Adzavon
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Fei Xie
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Yang Yi
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Xue Jiang
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Xiaokang Zhang
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Jin He
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Pengxiang Zhao
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Mengyu Liu
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Shiwen Ma
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China
| | - Xuemei Ma
- Faculty of Environment and Life, Beijing University of Technology, Beijing, 100124, People's Republic of China.
- Beijing Molecular Hydrogen Research Center, Beijing, 100124, People's Republic of China.
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Yuan G, Cen J, Liao J, Huang Y, Jie L. In situ hydrogen nanogenerator for bimodal imaging guided synergistic photothermal/hydrogen therapies. NANOSCALE 2021; 13:15576-15589. [PMID: 34524338 DOI: 10.1039/d1nr03260g] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Multifunctional nanoagents integrating multiple therapeutic and imaging functions hold promise in the field of non-invasive and precise tumor therapies. However, the complex preparation process and uncertain drug metabolism of nanoagents loaded with various therapeutic agents or imaging agents greatly hinder its clinical applications. Developing simple and effective nanoagents that integrate multiple therapeutic and imaging functions remain a huge challenge. Therefore, a novel strategy based on in situ hydrogen release is proposed in this work: aminoborane (AB) was loaded onto mesoporous polydopamine nanoparticles (MPDA NPs) as a prodrug for hydrogen production, and then, PEG was modified on the surface of nanoparticles (represented as AB@MPDA-PEG). MPDA NPs not only act as photothermal agents (PTA) with high photothermal conversion efficiency (808 nm, η = 38.72%) but also as the carriers of AB accumulated in the tumor through enhanced permeability and retention (EPR) effect. H2 gas generated by AB in the weak acid conditions of the tumor microenvironment (TME) not only was used to treat tumors via a combination of hydrogen and photothermal therapies but also serves as a US and CT contrast agent, providing accurate guidance for tumor treatment. Finally, in vivo and in vitro investigation suggest that the designed multifunctional nanosystem not only showed excellent properties such as high hydrogen-loading capacity, long-lasting sustained hydrogen release ability and excellent biocompatibility but also achieve selective PTT/hydrogen therapies and US/CT bimodal imaging functions, which can effectively guide antitumor therapies. The proposed hydrogen gas-based strategy for combination therapies and bimodal imaging integration holds promise as an efficient and safe tumor treatment for future clinical translation.
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Affiliation(s)
- Guanglong Yuan
- Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
| | - Jieqiong Cen
- Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
| | - Jiamin Liao
- Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
| | - Yuqin Huang
- Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
| | - Liu Jie
- Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China.
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11
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Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression. Int J Mol Sci 2021; 22:ijms22168724. [PMID: 34445428 PMCID: PMC8395776 DOI: 10.3390/ijms22168724] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 01/10/2023] Open
Abstract
While many antitumor drugs have yielded unsatisfactory therapeutic results, drugs are one of the most prevalent therapeutic measures for the treatment of cancer. The development of cancer largely results from mutations in nuclear DNA, as well as from those in mitochondrial DNA (mtDNA). Molecular hydrogen (H2), an inert molecule, can scavenge hydroxyl radicals (·OH), which are known to be the strongest oxidizing reactive oxygen species (ROS) in the body that causes these DNA mutations. It has been reported that H2 has no side effects, unlike conventional antitumor drugs, and that it is effective against many diseases caused by oxidative stress and chronic inflammation. Recently, there has been an increasing number of papers on the efficacy of H2 against cancer and its effects in mitigating the side effects of cancer treatment. In this review, we demonstrate the efficacy and safety of H2 as a novel antitumor agent and show that its mechanisms may not only involve the direct scavenging of ·OH, but also other indirect biological defense mechanisms via the regulation of gene expression.
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12
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Li H, Wu Z, Zhang J, Sun X, Duan F, Yao J, Sun M, Zhang J, Nie L. Instant Ultrasound-Evoked Precise Nanobubble Explosion and Deep Photodynamic Therapy for Tumors Guided by Molecular Imaging. ACS APPLIED MATERIALS & INTERFACES 2021; 13:21097-21107. [PMID: 33908256 DOI: 10.1021/acsami.1c05517] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Nanobubbles (NBs) have recently gained interest in cancer imaging and therapy due to the fact that nanoparticles with the size range of 1-1000 nm can extravasate into permeable tumor types through the enhanced permeability and retention (EPR) effect. However, the therapeutic study of NBs was only limited to drug delivery or cavitation. Herein, we developed ultrasound-evoked massive NB explosion to strikingly damage the surrounding cancer. The dual-function agent allows synergistic mechanical impact and photodynamic therapy of the tumors and enhances imaging contrast. Moreover, the mechanical explosion improved the light delivery efficiency in biological tissue to promote the effect of photodynamic therapy. Under ultrasound/photoacoustic imaging guidance, we induced on-the-spot bubble explosion and photodynamic therapy of tumors at a depth of centimeters in vivo. The mechanical impact of the explosion can enhance delivery of the photosensitizers. Ultrasound explicitly revealed the cancer morphology and exhibited fast NB perfusion. Generated mechanical damage and release of mixture agents demonstrated remarkable synergetic anticancer effects on deep tumors. This finding also offers a new approach and insight into treating cancers.
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Affiliation(s)
- Honghui Li
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Zhiyou Wu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
- Research Center of Medical Sciences & Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Jinde Zhang
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xiang Sun
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Fei Duan
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Junjie Yao
- Photoacoustic Imaging Laboratory, Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, United States
| | - Mingyang Sun
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People's Republic of China
| | - Jiaqiang Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People's Republic of China
| | - Liming Nie
- Research Center of Medical Sciences & Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
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13
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Terasaki Y, Terasaki M, Shimizu A. Protective Effects of Hydrogen against Irradiation. Curr Pharm Des 2021; 27:679-686. [PMID: 33463456 DOI: 10.2174/1381612827666210119103545] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 10/19/2020] [Indexed: 11/22/2022]
Abstract
Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H2O2, O2•-, ONOO-, and •OH. Molecular hydrogen (H2) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO-, and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H2 can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H2 treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H2-enriched water (for chronic). Thus, we had proposed that H2 be considered a potential radioprotective agent. Recent publications have shown that H2 directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H2 functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances in the treatment of H2 as a new class of radioprotective agents.
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Affiliation(s)
- Yasuhiro Terasaki
- Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
| | - Mika Terasaki
- Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
| | - Akira Shimizu
- Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan
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14
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Ohta S. Direct Targets and Subsequent Pathways for Molecular Hydrogen to Exert Multiple Functions: Focusing on Interventions in Radical Reactions. Curr Pharm Des 2021; 27:595-609. [PMID: 32767925 DOI: 10.2174/1381612826666200806101137] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2020] [Accepted: 05/27/2020] [Indexed: 01/10/2023]
Abstract
Molecular hydrogen (H2) was long regarded as non-functional in mammalian cells. We overturned the concept by demonstrating that H2 exhibits antioxidant effects and protects cells against oxidative stress. Subsequently, it has been revealed that H2 has multiple functions in addition to antioxidant effects, including antiinflammatory, anti-allergic functions, and as cell death and autophagy regulation. Additionally, H2 stimulates energy metabolism. As H2 does not readily react with most biomolecules without a catalyst, it is essential to identify the primary targets with which H2 reacts or interacts directly. As a first event, H2 may react directly with strong oxidants, such as hydroxyl radicals (•OH) in vivo. This review addresses the key issues related to this in vivo reaction. •OH may have a physiological role because it triggers a free radical chain reaction and may be involved in the regulation of Ca2+- or mitochondrial ATP-dependent K+-channeling. In the subsequent pathway, H2 suppressed a free radical chain reaction, leading to decreases in lipid peroxide and its end products. Derived from the peroxides, 4-hydroxy-2-nonenal functions as a mediator that up-regulates multiple functional PGC-1α. As the other direct target in vitro and in vivo, H2 intervenes in the free radical chain reaction to modify oxidized phospholipids, which may act as an antagonist of Ca2+-channels. The resulting suppression of Ca2+-signaling inactivates multiple functional NFAT and CREB transcription factors, which may explain H2 multi-functionality. This review also addresses the involvement of NFAT in the beneficial role of H2 in COVID-19, Alzheimer's disease and advanced cancer. We discuss some unsolved issues of H2 action on lipopolysaccharide signaling, MAPK and NF-κB pathways and the Nrf2 paradox. Finally, as a novel idea for the direct targeting of H2, this review introduces the possibility that H2 causes structural changes in proteins via hydrate water changes.
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Affiliation(s)
- Shigeo Ohta
- Department of Neurology Medicine, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan
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15
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Hancock JT, Russell G. Downstream Signalling from Molecular Hydrogen. PLANTS (BASEL, SWITZERLAND) 2021; 10:367. [PMID: 33672953 PMCID: PMC7918658 DOI: 10.3390/plants10020367] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/09/2021] [Accepted: 02/09/2021] [Indexed: 12/23/2022]
Abstract
Molecular hydrogen (H2) is now considered part of the suite of small molecules that can control cellular activity. As such, H2 has been suggested to be used in the therapy of diseases in humans and in plant science to enhance the growth and productivity of plants. Treatments of plants may involve the creation of hydrogen-rich water (HRW), which can then be applied to the foliage or roots systems of the plants. However, the molecular action of H2 remains elusive. It has been suggested that the presence of H2 may act as an antioxidant or on the antioxidant capacity of cells, perhaps through the scavenging of hydroxyl radicals. H2 may act through influencing heme oxygenase activity or through the interaction with reactive nitrogen species. However, controversy exists around all the mechanisms suggested. Here, the downstream mechanisms in which H2 may be involved are critically reviewed, with a particular emphasis on the H2 mitigation of stress responses. Hopefully, this review will provide insight that may inform future research in this area.
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Affiliation(s)
- John T. Hancock
- Department of Applied Sciences, University of the West of England, Bristol BS16 1QY, UK;
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16
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Cui X, Zhao Q, Huang Z, Xiao Y, Wan Y, Li S, Lee CS. Water-Splitting Based and Related Therapeutic Effects: Evolving Concepts, Progress, and Perspectives. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2020; 16:e2004551. [PMID: 33125185 DOI: 10.1002/smll.202004551] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 09/03/2020] [Indexed: 06/11/2023]
Abstract
Water-splitting has been extensively studied especially for energy applications. It is often not paid with enough attention for biomedical applications. In fact, several innovative breakthroughs have been achieved in the past few years by employing water-splitting for treating cancer and other diseases. Interestingly, among these important works, only two reports have mentioned the term "water-splitting." For this reason, the importance of water-splitting for biomedical applications is significantly underestimated. This progress work is written with the aims to explain and summarize how the principle of water-splitting is employed to achieve therapeutic results not offered by conventional approaches. It is expected that this progress report will not only explain the importance of water-splitting to scientists in the biomedical fields, it should also draw attention from scientists working on energy applications of water-splitting.
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Affiliation(s)
- Xiao Cui
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
| | - Qi Zhao
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
| | - Zhongming Huang
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
| | - Yafang Xiao
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
| | - Yingpeng Wan
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
| | - Shengliang Li
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
| | - Chun-Sing Lee
- Department of Chemistry, Institution Center of Super-Diamond and Advanced Films (COSDAF), City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, 999077, P. R. China
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17
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Hu Q, Zhou Y, Wu S, Wu W, Deng Y, Shao A. Molecular hydrogen: A potential radioprotective agent. Biomed Pharmacother 2020; 130:110589. [PMID: 32763820 DOI: 10.1016/j.biopha.2020.110589] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 07/25/2020] [Accepted: 07/28/2020] [Indexed: 02/07/2023] Open
Abstract
In recent years, many studies have shown that hydrogen has therapeutic and preventive effects on various diseases. Its selective antioxidant properties were well noticed. Most of the ionizing radiation-induced damage is caused by hydroxyl radicals (OH) from radiolysis of H2O. Since hydrogen can mitigate such damage through multiple mechanisms, it presents noteworthy potential as a novel radio-protective agent. This review analyses possible mechanisms for hydrogen's radioprotective properties and effective delivery methods. We also look into details of vitro and vivo studies for hydrogen's radioprotective effects, and clinical practices. We conclude that hydrogen has good potential in radio-protection, with evidence that warrants greater research efforts in this field.
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Affiliation(s)
- Qiongge Hu
- Department of Radiation Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yunxiang Zhou
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shijie Wu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wei Wu
- Department of Medical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yongchuan Deng
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Anwen Shao
- Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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18
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Qiu X, Dong K, Guan J, He J. Hydrogen attenuates radiation-induced intestinal damage by reducing oxidative stress and inflammatory response. Int Immunopharmacol 2020; 84:106517. [PMID: 32361189 DOI: 10.1016/j.intimp.2020.106517] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/13/2020] [Accepted: 04/13/2020] [Indexed: 01/23/2023]
Abstract
The small intestine is known to be particularly sensitive to radiation, and the major limiting factor of radiotherapy is the gastrointestinal syndrome that subsequently develops after its administration. The detrimental effects of radiation are mostly mediated via the overproduction of reactive oxygen species (ROS), especially the hydroxyl radical (·OH). Because hydrogen is a selective ·OH scavenger, we hypothesized that hydrogen might exert a protective effect against radiation-induced intestinal damage. Herein, radiation models were built both in mice and in an intestinal crypt epithelial cell (IEC-6) line. In the animal experiment, we demonstrated that hydrogen-rich saline significantly reduced radiation-induced intestinal mucosal damage, improved intestinal function, and increased the survival rate. In addition, radiation-induced oxidative stress damage and systemic inflammatory response were also mitigated by hydrogen treatment. Moreover, hydrogen treatment decreased cell apoptosis and maintained intestinal epithelial cell proliferation in mice. In vitro experiments using the IEC-6 cell line showed that hydrogen-rich medium significantly inhibited ROS formation, maintained cell viability, and inhibited cell apoptosis. Importantly, hydrogen treatment prevented mitochondrial depolarization, cytochrome c release, and activity of caspase-3, caspase-9, and PARP. Moreover, the decreased expression of Bcl-xl and Bcl-2 and the increased expression of Bax protein were also blocked by hydrogen treatment. In conclusion, our study concurrently demonstrated that hydrogen provides an obviously protective effect on radiation-induced intestinal and cell injuries. Our work demonstrated that this protective effect might be due to the blockage of the mitochondrial apoptotic pathway.
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Affiliation(s)
- Xiaochen Qiu
- Department of General Surgery, The Eighth Medical Center, Chinese PLA(People's Liberation Army) General Hospital, Beijing 100091, China
| | - Kaisheng Dong
- Department of Oncology, The Eighth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100091, China; Postgraduate Department of Hebei North University, Zhangjiakou 075000, China
| | - Jingzhi Guan
- Department of Oncology, The Eighth Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100091, China
| | - JianMiao He
- Department of General Surgery, The Eighth Medical Center, Chinese PLA(People's Liberation Army) General Hospital, Beijing 100091, China.
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19
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Phan TTV, Huynh TC, Manivasagan P, Mondal S, Oh J. An Up-To-Date Review on Biomedical Applications of Palladium Nanoparticles. NANOMATERIALS (BASEL, SWITZERLAND) 2019; 10:E66. [PMID: 31892149 PMCID: PMC7023275 DOI: 10.3390/nano10010066] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 12/20/2019] [Accepted: 12/23/2019] [Indexed: 12/28/2022]
Abstract
Palladium nanoparticles (PdNPs) have intrinsic features, such as brilliant catalytic, electronic, physical, mechanical, and optical properties, as well as diversity in shape and size. The initial researches proved that PdNPs have impressive potential for the development of novel photothermal agents, photoacoustic agents, antimicrobial/antitumor agents, gene/drug carriers, prodrug activators, and biosensors. However, very few studies have taken the benefit of the unique characteristics of PdNPs for applications in the biomedical field in comparison with other metals like gold, silver, or iron. Thus, this review aims to highlight the potential applications in the biomedical field of PdNPs. From that, the review provides the perceptual vision for the future development of PdNPs in this field.
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Affiliation(s)
- Thi Tuong Vy Phan
- Center for Advanced Chemistry, Institute of Research and Development, Duy Tan University, 03 Quang Trung, Hai Chau, Danang 550000, Vietnam;
| | - Thanh-Canh Huynh
- Center for Construction, Mechanics and Materials, Institute of Research and Development, Duy Tan University, 03 Quang Trung, Hai Chau, Danang 550000, Vietnam;
| | - Panchanathan Manivasagan
- Center for Marine-Integrated Biomedical Technology, Pukyong National University, Busan 48513, Korea; (P.M.); (S.M.)
| | - Sudip Mondal
- Center for Marine-Integrated Biomedical Technology, Pukyong National University, Busan 48513, Korea; (P.M.); (S.M.)
| | - Junghwan Oh
- Center for Marine-Integrated Biomedical Technology, Pukyong National University, Busan 48513, Korea; (P.M.); (S.M.)
- Department of Biomedical Engineering, Pukyong National University, Busan 48513, Korea
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20
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Tao G, Song G, Qin S. Molecular hydrogen: current knowledge on mechanism in alleviating free radical damage and diseases. Acta Biochim Biophys Sin (Shanghai) 2019; 51:1189-1197. [PMID: 31738389 DOI: 10.1093/abbs/gmz121] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 09/20/2019] [Accepted: 08/30/2019] [Indexed: 12/11/2022] Open
Abstract
Ever since molecular hydrogen was first reported as a hydroxyl radical scavenger in 2007, the beneficial effect of hydrogen was documented in more than 170 disease models and human diseases including ischemia/reperfusion injury, metabolic syndrome, inflammation, and cancer. All these pathological damages are concomitant with overproduction of reactive oxygen species (ROS) where molecular hydrogen has been widely demonstrated as a selective antioxidant. Although it is difficult to construe the molecular mechanism of hydrogen's biomedical effect, an increasing number of studies have been helping us draw the picture clearer with days passing by. In this review, we summarized the current knowledge on systemic and cellular modulation by hydrogen treatment. We discussed the antioxidative, anti-inflammatory, and anti-apoptosis effects of hydrogen, as well as its protection on mitochondria and the endoplasmic reticulum, regulation of intracellular signaling pathways, and balancing of the immune cell subtypes. We hope that this review will provide organized information that prompts further investigation for in-depth studies of hydrogen effect.
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Affiliation(s)
- Geru Tao
- Key Laboratory of Atherosclerosis in University of Shandong, Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271000, China
| | - Guohua Song
- Key Laboratory of Atherosclerosis in University of Shandong, Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271000, China
| | - Shucun Qin
- Key Laboratory of Atherosclerosis in University of Shandong, Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an 271000, China
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21
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Mikami T, Tano K, Lee H, Lee H, Park J, Ohta F, LeBaron TW, Ohta S. Drinking hydrogen water enhances endurance and relieves psychometric fatigue: a randomized, double-blind, placebo-controlled study 1. Can J Physiol Pharmacol 2019; 97:857-862. [PMID: 31251888 DOI: 10.1139/cjpp-2019-0059] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Acute physical exercise increases reactive oxygen species in skeletal muscle, leading to tissue damage and fatigue. Molecular hydrogen (H2) acts as a therapeutic antioxidant directly or indirectly by inducing antioxidative enzymes. Here, we examined the effects of drinking H2 water (H2-infused water) on psychometric fatigue and endurance capacity in a randomized, double-blind, placebo-controlled fashion. In Experiment 1, all participants drank only placebo water in the first cycle ergometer exercise session, and for comparison they drank either H2 water or placebo water 30 min before exercise in the second examination. In these healthy non-trained participants (n = 99), psychometric fatigue judged by visual analogue scales was significantly decreased in the H2 group after mild exercise. When each group was divided into 2 subgroups, the subgroup with higher visual analogue scale values was more sensitive to the effect of H2. In Experiment 2, trained participants (n = 60) were subjected to moderate exercise by cycle ergometer in a similar way as in Experiment 1, but exercise was performed 10 min after drinking H2 water. Endurance and fatigue were significantly improved in the H2 group as judged by maximal oxygen consumption and Borg's scale, respectively. Taken together, drinking H2 water just before exercise exhibited anti-fatigue and endurance effects.
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Affiliation(s)
- Toshio Mikami
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Kohei Tano
- Fitness Club, Asahi Big S Mukogaoka, Kawasaki-city, Kanagawa pref. 214-0014, Japan
| | - Hosung Lee
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Hyowon Lee
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Jonghyuk Park
- Department of Health and Sports Science, Nippon Medical School, Musashino, Tokyo 180-0023, Japan
| | - Fumiaki Ohta
- Hydrogen Health Medical Laboratory, Co., Ltd., Arakawa-ku, Tokyo 116-0001, Japan
| | - Tyler W LeBaron
- Slovak Academy of Sciences, Centre of Experimental Medicine, Institute for Heart Research, Bratislava 84005, Slovak Republic.,Molecular Hydrogen Institute, Enoch, UT 84721, USA
| | - Shigeo Ohta
- Department of Neurology Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
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22
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LeBaron TW, Kura B, Kalocayova B, Tribulova N, Slezak J. A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress. Molecules 2019; 24:E2076. [PMID: 31159153 PMCID: PMC6600250 DOI: 10.3390/molecules24112076] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 05/20/2019] [Accepted: 05/24/2019] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular diseases are the most common causes of morbidity and mortality worldwide. Redox dysregulation and a dyshomeostasis of inflammation arise from, and result in, cellular aberrations and pathological conditions, which lead to cardiovascular diseases. Despite years of intensive research, there is still no safe and effective method for their prevention and treatment. Recently, molecular hydrogen has been investigated in preclinical and clinical studies on various diseases associated with oxidative and inflammatory stress such as radiation-induced heart disease, ischemia-reperfusion injury, myocardial and brain infarction, storage of the heart, heart transplantation, etc. Hydrogen is primarily administered via inhalation, drinking hydrogen-rich water, or injection of hydrogen-rich saline. It favorably modulates signal transduction and gene expression resulting in suppression of proinflammatory cytokines, excess ROS production, and in the activation of the Nrf2 antioxidant transcription factor. Although H2 appears to be an important biological molecule with anti-oxidant, anti-inflammatory, and anti-apoptotic effects, the exact mechanisms of action remain elusive. There is no reported clinical toxicity; however, some data suggests that H2 has a mild hormetic-like effect, which likely mediate some of its benefits. The mechanistic data, coupled with the pre-clinical and clinical studies, suggest that H2 may be useful for ROS/inflammation-induced cardiotoxicity and other conditions.
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Affiliation(s)
- Tyler W LeBaron
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
- Molecular Hydrogen Institute, Enoch City, UT, 847 21, USA.
| | - Branislav Kura
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
| | - Barbora Kalocayova
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
| | - Narcis Tribulova
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
| | - Jan Slezak
- Centre of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava 841 04, Slovak Republic.
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Liu MY, Xie F, Zhang Y, Wang TT, Ma SN, Zhao PX, Zhang X, Lebaron TW, Yan XL, Ma XM. Molecular hydrogen suppresses glioblastoma growth via inducing the glioma stem-like cell differentiation. Stem Cell Res Ther 2019; 10:145. [PMID: 31113492 PMCID: PMC6528353 DOI: 10.1186/s13287-019-1241-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 03/12/2019] [Accepted: 04/22/2019] [Indexed: 12/30/2022] Open
Abstract
Background Glioblastoma (GBM) is the most common type of primary malignant brain tumor. Molecular hydrogen has been considered a preventive and therapeutic medical gas in many diseases including cancer. In our study, we sought to assess the potential role of molecular hydrogen on GBM. Methods The in vivo studies were performed using a rat orthotopic glioma model and a mouse subcutaneous xenograft model. Animals inhaled hydrogen gas (67%) 1 h two times per day. MR imaging studies were performed to determine the tumor volume. Immunohistochemistry (IHC), immunofluorescence staining, and flow cytometry analysis were conducted to determine the expression of surface markers. Sphere formation assay was performed to assess the cancer stem cell self-renewal capacity. Assays for cell migration, invasion, and colony formation were conducted. Results The in vivo study showed that hydrogen inhalation could effectively suppress GBM tumor growth and prolong the survival of mice with GBM. IHC and immunofluorescence staining demonstrated that hydrogen treatment markedly downregulated the expression of markers involved in stemness (CD133, Nestin), proliferation (ki67), and angiogenesis (CD34) and also upregulated GFAP expression, a marker of differentiation. Similar results were obtained in the in vitro studies. The sphere-forming ability of glioma cells was also suppressed by hydrogen treatment. Moreover, hydrogen treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. Conclusions Together, these results indicated that molecular hydrogen may serve as a potential anti-tumor agent in the treatment of GBM.
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Affiliation(s)
- Meng-Yu Liu
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China.,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China
| | - Fei Xie
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China.,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China
| | - Yan Zhang
- Affiliated Bayi Brain Hospital, The Seventh Medical Center of PLA General Hospital, Beijing, 100700, China
| | - Ting-Ting Wang
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China.,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China
| | - Sheng-Nan Ma
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China.,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China
| | - Peng-Xiang Zhao
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China.,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China
| | - Xin Zhang
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China.,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China
| | - Tyler W Lebaron
- Correction is Molecular Hydrogen Institute, Enoch, UT, USA.,Center of Experimental Medicine, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic
| | - Xin-Long Yan
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China. .,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China.
| | - Xue-Mei Ma
- College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, 100124, China. .,Beijing Molecular Hydrogen Research Center, Beijing, 100124, China.
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Kou Z, Zhao P, Wang Z, Jin Z, Chen L, Su BL, He Q. Acid-responsive H 2-releasing Fe nanoparticles for safe and effective cancer therapy. J Mater Chem B 2019; 7:2759-2765. [PMID: 32255077 DOI: 10.1039/c9tb00338j] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hydrogen therapy is an emerging and promising strategy for treatment of inflammation-related diseases owing to the excellent bio-safety of hydrogen molecules (H2), but is facing a challenge that the H2 concentration at the local disease site is hardly accumulated because of its high diffusibility and low solubility, limiting the efficacy of hydrogen therapy. Herein, we propose a nanomedicine strategy of imaging-guided tumour-targeted delivery and tumour microenvironment-triggered release of H2 to address this issue, and develop a kind of biocompatible carboxymethyl cellulose (CMC)-coated/stabilized Fe (Fe@CMC) nanoparticle with photoacoustic imaging (PAI), tumour targeting and acid responsive hydrogen release properties for cancer therapy. The Fe@CMC nanoparticles have demonstrated high intratumoural accumulation capability, high acid responsiveness, excellent PAI performance, selective cancer-killing effect and high bio-safety in vitro and in vivo. Effective inhibition of tumour growth is achieved by intravenous injection of the Fe@CMC nanoparticles, and the selective anti-cancer mechanism of Fe@CMC is discovered to be originated from the energy metabolism homeostasis regulatory function of the released H2. The proposed nanomedicine-mediated hydrogen therapy strategy will open a new window for precise, high-efficacy and safe cancer treatment.
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Affiliation(s)
- Zhu Kou
- Laboratory of Living Materials, The State Key Laboratory of Advanced Technology for Marterials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, 430070, Wuhan, China.
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25
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LeBaron TW, Larson AJ, Ohta S, Mikami T, Barlow J, Bulloch J, DeBeliso M. Acute Supplementation with Molecular Hydrogen Benefits Submaximal Exercise Indices. Randomized, Double-Blinded, Placebo-Controlled Crossover Pilot Study. J Lifestyle Med 2019; 9:36-43. [PMID: 30918832 PMCID: PMC6425901 DOI: 10.15280/jlm.2019.9.1.36] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/22/2018] [Indexed: 12/31/2022] Open
Abstract
Background Clinical studies have reported hydrogen-rich water (HRW) to have therapeutic and ergogenic effects. The aim of this study was to determine the effect of acute supplementation with HRW on exercise performance as measured by VO2, respiratory exchange ratio (RER), heart rate (HR), and respiratory rate (RR). Methods Baseline levels of all exercise indices were determined in nineteen (4 female, 23.4 ± 9.1 yr; 15 male, 30.5 ± 6.8 yr) healthy subjects using a graded treadmill exercise test to exhaustion. Each subject was examined two additional times in a randomized double-blinded, placebo-controlled crossover fashion. Subjects received either HRW or placebo, which was consumed the day before and the day of the testing. HRW was delivered using the hydrogen-producing tablets, DrinkHRW (5 mg of H2). All data was analyzed with SPSS using pairwise comparisons with Bonferroni adjustment. Results HRW supplementation did not influence maximal or minimal indices of exercise performance (VO2, RER, HR and RR) (p < 0.05). However, HRW significantly decreased average exercising RR and HR (p < 0.05). HRW decreased exercising HR during minutes 1–9 of the graded exercise test (121 ± 26 bpm) compared to placebo (126 ± 26 bpm) and baseline (124 ± 27 bpm) (p < 0.001) without substantially influencing VO2. Conclusion Acute supplementation of DrinkHRW tablets may benefit submaximal aerobic exercise performance by lowering exercising HR. Further studies are needed to determine the influence and practical significance of HRW on varying exercise intensities as well as optimal dosing protocols and the effects of chronic use.
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Affiliation(s)
- Tyler W LeBaron
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA.,Molecular Hydrogen Institute, UT, USA.,Slovak Academy of Sciences, Centre of Experimental Medicine, Institute for Heart Research, Bratislava, Slovakia
| | - Abigail J Larson
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
| | - Shigeo Ohta
- Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
| | - Toshio Mikami
- Department of Sport Science, Nippon Medical School, Tokyo, Japan
| | - Jordon Barlow
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
| | - Josh Bulloch
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
| | - Mark DeBeliso
- Department of Kinesiology and Outdoor Recreation, Southern Utah University, UT, USA
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26
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Mo XY, Li XM, She CS, Lu XQ, Xiao CG, Wang SH, Huang GQ. Hydrogen-rich saline protects rat from oxygen glucose deprivation and reperusion-induced apoptosis through VDAC1 via Bcl-2. Brain Res 2018; 1706:110-115. [PMID: 30287344 DOI: 10.1016/j.brainres.2018.09.037] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 08/31/2018] [Accepted: 09/30/2018] [Indexed: 11/17/2022]
Abstract
BACKGROUND Hydrogen is received as an inert gas that thought to be non-functional in vivo previously. Recently, emerging evidences showed that in ischemia/reperfusion (IR) condition, hydrogen reduced cellular reactive oxygen species (ROS) production and ameliorated cell apoptosis. However, the underlying mechanism of hydrogen on IR-induced apoptosis remains elusive. Here we tried to unravel the mode of action of hydrogen with rat adrenal medulla cell line PC-12 in vitro. METHODS The mitochondrial functions before and after oxygen glucose deprivation and reperfusion (OGD/RP) were determined with corresponding dyes. The expression of Bcl-2, Bax, VDAC1, cytochrome c and caspase 9 was detected using qRT-PCR and Western Blotting method. Then Bcl-2 inhibitor, AB-199, was applied to investigate the role of Bcl-2 in OGD/RP-induced cell apoptosis. Finally, we manipulated the expression of VDAC1 with plasmids transfection to understand the effects of VDAC1 on Bcl-2-mediated anti-apoptosis in OGD/RP. RESULTS In this study, we demonstrated that hydrogen-rich saline (HRS) reduced OGD/RP-mediated neuronal loss by stimulating the expression of Bcl-2, which suppressed the activity of VDAC1. Consequently, HRS maintained the mitochondrial functions, restrained the release of cytochrome c and caspase 9 activation, resulting in ameliorated cell viability. CONCLUSIONS HRS ameliorated OGD/RP-induced PC-12 cell apoptosis and provided a novel treatment option for ischemia.
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Affiliation(s)
- Xiao-Ye Mo
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China
| | - Xiang-Min Li
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China
| | - Chang-Shou She
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China
| | - Xiao-Qin Lu
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China
| | - Cheng-Gen Xiao
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China
| | - Shi-Hai Wang
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China
| | - Guo-Qing Huang
- Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, PR China.
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27
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Liu S, Oshita S, Thuyet DQ, Saito M, Yoshimoto T. Antioxidant Activity of Hydrogen Nanobubbles in Water with Different Reactive Oxygen Species both in Vivo and in Vitro. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2018; 34:11878-11885. [PMID: 30189133 DOI: 10.1021/acs.langmuir.8b02440] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Hydrogen water as a new therapeutic antioxidant has been widely used in living organisms under stress. In this study, we applied nanobubble (NB) technology to hydrogen water. The antioxidant capacity of hydrogen NB water was studied with respect to different reactive oxygen species (ROS) both in vitro and in vivo. Using a relatively weak reduced dye, APF, we showed that hydrogen NB water can effectively remove three cytotoxic ROS, •OH, ClO-, and ONOO-, from water. Hydrogen NB water could also remove O2•-, which is a physiologically important ROS, from water. However, hydrogen water could not reduce other physiologically important ROS such as H2O2 and NO. At similar dissolved hydrogen concentrations, hydrogen NB water displayed higher antioxidant activity than hydrogen water without NB. Barley seed germination tests were used to study the antioxidant effect of hydrogen NB water on ROS generation in vivo. Our results showed that this decreased the physiological activity of barley seeds in their normal homeostatic state. Hydrogen NB water eliminated endogenous O2•- in seeds and inhibited germination. The usage of hydrogen NB water should be individually considered according to the types of cells involved. Our results offer basic data concerning the application of hydrogen NB water in different fields.
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Affiliation(s)
- Shu Liu
- Department of Environmental Science and Engineering, School of Space and Environment , Beihang University , Beijing 100191 , China
- Graduate School of Agricultural & Life Sciences , The University of Tokyo , Yayoi 1-1-1 , Bunkyo-ku, Tokyo 113-8657 , Japan
| | - Seiichi Oshita
- Graduate School of Agricultural & Life Sciences , The University of Tokyo , Yayoi 1-1-1 , Bunkyo-ku, Tokyo 113-8657 , Japan
| | - Dang Quoc Thuyet
- Graduate School of Agricultural & Life Sciences , The University of Tokyo , Yayoi 1-1-1 , Bunkyo-ku, Tokyo 113-8657 , Japan
| | - Masanao Saito
- Graduate School of Agricultural & Life Sciences , The University of Tokyo , Yayoi 1-1-1 , Bunkyo-ku, Tokyo 113-8657 , Japan
| | - Takahiko Yoshimoto
- Graduate School of Agricultural & Life Sciences , The University of Tokyo , Yayoi 1-1-1 , Bunkyo-ku, Tokyo 113-8657 , Japan
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Jiang Y, Liu G, Zhang L, Cheng S, Luo C, Liao Y, Guo S. Therapeutic efficacy of hydrogen‑rich saline alone and in combination with PI3K inhibitor in non‑small cell lung cancer. Mol Med Rep 2018; 18:2182-2190. [PMID: 29901139 PMCID: PMC6072234 DOI: 10.3892/mmr.2018.9168] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 06/07/2018] [Indexed: 12/15/2022] Open
Abstract
The aim of the present study was to investigate the effects of combination therapy of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), with hydrogen-rich saline on the proliferation and apoptosis of the non-small cell lung cancer (NSCLC) A549 cell line and the mechanisms underpinning this. Excessive production of reactive oxygen species (ROS) may induce DNA mutations, DNA damage, genomic instability and cell proliferation, and ROS are involved in several types of cancer, particularly lung cancer. In a previous study, hydrogen was recognized as an antioxidant in preventive and therapeutic applications. The PI3K/protein kinase B (Akt) pathway is an important signaling pathway that may activate downstream of a series of extracellular signals and impact on cellular processes including cell proliferation, apoptosis and survival. To date, the PI3K/Akt signaling pathway has been indicated as a feasible target for novel antineoplastic drugs. Different strategies combining the two treatment modalities have been used in cancer therapy in order to achieve an improved therapeutic response and longer control of tumor modalities control. The present study investigated the effect of hydrogen-rich saline alone and in combination with the PI3K inhibitor, LY294002, on the proliferation, oxidative stress and apoptosis of NSCLC A549 cells. This combination therapy may be more effective than separate drug treatment; it decreased the malondialdehyde level and increased the superoxide dismutase activity. The combination therapy also enhanced the efficacy of anti-proliferation and apoptosis. Similarly, the results of the present study demonstrated that administration of the two agents in combination may inhibit phospho-Akt activity, and reduce expression of heme oxygenase-1 and nuclear factor-κB p65. The results further suggested that the combination therapy may reduce cell proliferation and promote cell apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K pathway in NSCLC cell lines. Therefore, the present study provided evidence that combined therapy may be a novel therapeutic option for patients with NSCLC.
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Affiliation(s)
- Yu Jiang
- Department of Respiratory Medicine, The University‑Town Hospital Affiliated to Chongqing Medical University, Chongqing 401331, P.R. China
| | - Gang Liu
- Department of Respiratory Medicine, The University‑Town Hospital Affiliated to Chongqing Medical University, Chongqing 401331, P.R. China
| | - Li Zhang
- Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Sheng Cheng
- Department of Respiratory Medicine, The University‑Town Hospital Affiliated to Chongqing Medical University, Chongqing 401331, P.R. China
| | - Chun Luo
- Department of Respiratory Medicine, The University‑Town Hospital Affiliated to Chongqing Medical University, Chongqing 401331, P.R. China
| | - Yang Liao
- Department of Respiratory Medicine, The University‑Town Hospital Affiliated to Chongqing Medical University, Chongqing 401331, P.R. China
| | - Shuliang Guo
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
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29
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Krezdorn N, Tasigiorgos S, Wo L, Turk M, Lopdrup R, Kiwanuka H, Win TS, Bueno E, Pomahac B. Tissue conservation for transplantation. Innov Surg Sci 2017; 2:171-187. [PMID: 31579751 PMCID: PMC6754021 DOI: 10.1515/iss-2017-0010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 06/27/2017] [Indexed: 02/07/2023] Open
Abstract
Pathophysiological changes that occur during ischemia and subsequent reperfusion cause damage to tissues procured for transplantation and also affect long-term allograft function and survival. The proper preservation of organs before transplantation is a must to limit these injuries as much as possible. For decades, static cold storage has been the gold standard for organ preservation, with mechanical perfusion developing as a promising alternative only recently. The current literature points to the need of developing dedicated preservation protocols for every organ, which in combination with other interventions such as ischemic preconditioning and therapeutic additives offer the possibility of improving organ preservation and extending it to multiple times its current duration. This review strives to present an overview of the current body of knowledge with regard to the preservation of organs and tissues destined for transplantation.
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Affiliation(s)
- Nicco Krezdorn
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Burn Center, Hannover Medical School, Hannover, Germany
| | - Sotirios Tasigiorgos
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Luccie Wo
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Marvee Turk
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Rachel Lopdrup
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Harriet Kiwanuka
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Thet-Su Win
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Ericka Bueno
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Bohdan Pomahac
- Department of Surgery, Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
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Nakayama M, Itami N, Suzuki H, Hamada H, Osaka N, Yamamoto R, Tsunoda K, Nakano H, Watanabe K, Zhu WJ, Maruyama Y, Terawaki H, Kabayama S, Nakazawa R, Miyazaki M, Ito S. Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients: Interim analysis in a 12 month observation. PLoS One 2017; 12:e0184535. [PMID: 28902900 PMCID: PMC5597210 DOI: 10.1371/journal.pone.0184535] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 08/12/2017] [Indexed: 01/10/2023] Open
Abstract
Background and aim It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation. Subjects and method 262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups. Results In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors. Conclusion The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment.
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Affiliation(s)
- Masaaki Nakayama
- United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Tohoku University, Sendai, Japan
- Research Division of Chronic Kidney Disease and Dialysis Treatment, Tohoku University Hospital, Sendai, Japan
- Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima, Japan
- * E-mail:
| | - Noritomo Itami
- Kidney Center, Nikko-Memorial Hospital and Higashi Muroran Satellite Clinic, Muroran, Japan
| | | | - Hiromi Hamada
- Kidney Center, Nikko-Memorial Hospital and Higashi Muroran Satellite Clinic, Muroran, Japan
| | | | | | | | | | - Kimio Watanabe
- United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Tohoku University, Sendai, Japan
| | - Wan-Jun Zhu
- United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Tohoku University, Sendai, Japan
- Research Division of Chronic Kidney Disease and Dialysis Treatment, Tohoku University Hospital, Sendai, Japan
- Trim Medical Institute Co., Ltd., Osaka, Japan
| | - Yukio Maruyama
- Department of Nephrology and Hypertension, The Tokyo Jikei University School of Medicine, Tokyo, Japan
| | - Hiroyuki Terawaki
- Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima, Japan
| | - Shigeru Kabayama
- United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Tohoku University, Sendai, Japan
- Trim Medical Institute Co., Ltd., Osaka, Japan
| | | | - Mariko Miyazaki
- United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Tohoku University, Sendai, Japan
- Research Division of Chronic Kidney Disease and Dialysis Treatment, Tohoku University Hospital, Sendai, Japan
- Division of Blood purification, Tohoku University Hospital, Sendai, Japan
| | - Sadayoshi Ito
- United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Tohoku University, Sendai, Japan
- Division of Blood purification, Tohoku University Hospital, Sendai, Japan
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31
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Huang JL, Zhao BL, Manaenko A, Liu F, Sun XJ, Hu Q. Medical gases for stroke therapy: summary of progress 2015-2016. Med Gas Res 2017; 7:107-112. [PMID: 28744363 PMCID: PMC5510291 DOI: 10.4103/2045-9912.208516] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Stroke is a cerebrovascular disease with high mortality and morbidity. Despite extensive research, there are only a very limited number of therapeutic approaches suitable for treatment of stroke patients as yet. Mounting evidence has demonstrated that such gases as oxygen, hydrogen and hydrogen sulfide are able to provide neuroprotection after stroke. In this paper, we will focus on the recent two years’ progress in the development of gas therapies of stroke and in understanding the molecular mechanisms underlying protection induced by medical gases. We will also discuss the advantages and challenges of these approaches and provide information for future study.
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Affiliation(s)
- Jun-Long Huang
- Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Navy Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Bao-Lian Zhao
- Department of Navy Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Anatol Manaenko
- Departments of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany
| | - Fan Liu
- Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xue-Jun Sun
- Department of Navy Aeromedicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
| | - Qin Hu
- Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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32
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Zhang X, Liu J, Jin K, Xu H, Wang C, Zhang Z, Kong M, Zhang Z, Wang Q, Wang F. Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes. J Diabetes Investig 2017; 9:83-90. [PMID: 28390099 PMCID: PMC5754517 DOI: 10.1111/jdi.12674] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 03/11/2017] [Accepted: 04/03/2017] [Indexed: 02/06/2023] Open
Abstract
Aims/Introduction In previous studies, hydrogen gas (H2) administration has clearly shown effectiveness in inhibiting diabetes. Here, we evaluated whether subcutaneous injection of H2 shows enhanced efficacy against type 2 diabetes mellitus induced in mice by a high‐fat diet and low‐dose streptozotocin treatment. Material and Methods H2 was injected subcutaneously at a dose of 1 mL/mouse/week for 4 weeks. Type 2 diabetes mellitus‐associated parameters were then evaluated to determine the effectiveness of subcutaneous H2 administration. Results The bodyweight of H2‐treated mice did not change over the course of the experiment. Compared with the untreated control animals, glucose, insulin, low‐density lipoprotein and triglyceride levels in the serum were significantly lower in treated mice, whereas high‐density lipoprotein cholesterol in the serum was significantly higher. Glucose tolerance and insulin sensitivity were both improved in H2‐treated mice. Diabetic nephropathy analysis showed significant reductions in urine volume, urinary total protein and β2‐microglobulin, kidney/bodyweight ratio, and kidney fibrosis associated with subcutaneous injection of H2. Conclusions Subcutaneous injection of H2 significantly improves type 2 diabetes mellitus and diabetic nephropathy‐related outcomes in a mouse model, supporting further consideration of subcutaneous injection as a novel and effective route of clinical H2 administration.
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Affiliation(s)
- Xiaolong Zhang
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Jiaming Liu
- Department of Preventive Medicine, School of Environmental Science and Management, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Keke Jin
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Haifeng Xu
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Chuang Wang
- Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, Ningbo, Zhejiang Province, China
| | - Zhuang Zhang
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Mimi Kong
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Zhengzheng Zhang
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Qingyi Wang
- Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Fangyan Wang
- Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
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Abstract
BACKGROUND Reactive oxygen species (ROS) are often associated with persistent pains such as neuropathic and inflammatory pain. Hydrogen gas can reduce ROS and alleviate cerebral, myocardial, and hepatic ischemia/reperfusion injuries. In the present study, we aim to investigate whether hydrogen-rich saline can reduce neuropathic pain in a rat model of chronic constriction injury (CCI). METHODS Thirty SD rats were randomly divided into three groups: sham group was administered sodium chloride by intrathecal injection (n=10); control groups underwent CCI surgery and were administered sodium chloride by intrathecal injection (n=10); vehicle group underwent CCI surgery and was administered hydrogen-rich saline by intrathecal injection (n=10). Drugs were administered in the dose of 100 ul/kg once a day at 0.5 hours before and 1-7 day after CCI surgery. The mechanical thresholds were tested at one day before and 3-14 day after CCI surgery. RESULTS We found that hydrogen-rich saline significantly elevated the mechanical thresholds of neuropathic pain compared to vehicle (physiologic saline) control in CCI rats (p<0.05); it also decreased the levels of myeloperoxidase, maleic dialdehyde, and protein carbonyl in spinal cord by 7 days post-chronic constriction injury(p<0.05). In addition, hydrogen-rich saline also suppressed the expression of p38-mitogen-activated protein kinase (p38MAPK) and brain-derived neurotrophic factor (BDNF) in the spinal cord by 7 days post-chronic constriction injury (p<0.01, p<0.01, respectively), but had no effect on P2X4R (p>0.05), an ATP receptor. CONCLUSION Intrathecal injection of hydrogen-rich saline can decrease oxidative stress and the expression of p38MAPK and BDNF that may contribute to the elevated threshold of neuropathic pain in rat CCI model. Le salin riche en hydrogène atténue la douleur névropathique en réduisant le stress oxydatif.
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Chen Y, Zong C, Guo Y, Tian L. Hydrogen-rich saline may be an effective and specific novel treatment for osteoradionecrosis of the jaw. Ther Clin Risk Manag 2015; 11:1581-5. [PMID: 26508867 PMCID: PMC4610769 DOI: 10.2147/tcrm.s90770] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Hydrogen, a therapeutic medical gas, can exert antioxidant activity via selectively reducing cytotoxic reactive oxygen species such as hydroxyl radicals. Hydrogen-rich saline is an alternative form of molecular hydrogen that has been widely used in many studies, including metabolic syndrome, cerebral, hepatic, myocardial ischemia/reperfusion, and liver injuries with obstructive jaundice, with beneficial results. Osteoradionecrosis of the jaw is a serious complication following radiotherapy for head and neck cancers. It has long been known that most radiation-induced symptoms are caused by free radicals generated by radiolysis of H2O, and the hydroxyl radical is the most reactive of these. Reducing the hydroxyl radical can distinctly improve the protection of cells from radiation damage. We hypothesized that hydrogen-rich saline might be an effective and specific method of managing and preventing osteoradionecrosis of the jaw.
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Affiliation(s)
- Yuanli Chen
- Department of Cranio-facial Trauma and Orthognathic Surgery Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, People's Republic of China
| | - Chunlin Zong
- Department of Cranio-facial Trauma and Orthognathic Surgery Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, People's Republic of China
| | - Yuxuan Guo
- Department of Cranio-facial Trauma and Orthognathic Surgery Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, People's Republic of China
| | - Lei Tian
- Department of Cranio-facial Trauma and Orthognathic Surgery Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Shaanxi Key Laboratory of Stomatology, Xi'an, People's Republic of China
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Zhai Y, Zhou X, Dai Q, Fan Y, Huang X. Hydrogen-rich saline ameliorates lung injury associated with cecal ligation and puncture-induced sepsis in rats. Exp Mol Pathol 2015; 98:268-76. [PMID: 25746665 DOI: 10.1016/j.yexmp.2015.03.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2014] [Revised: 12/16/2014] [Accepted: 03/02/2015] [Indexed: 10/23/2022]
Abstract
AIMS Although hydrogen has been proved to be a novel therapeutic medical gas in several lung injury animal models, to our knowledge, it has not been tested yet in acute lung injury (ALI) induced by cecal ligation and puncture (CLP). This study was to investigate the hypothesis that hydrogen could ameliorate CLP-induced lung injury in rats. METHODS AND RESULTS Our experiments exhibited that gas exchange dysfunction and lung tissue inflammation were observed in animals exposed to CLP. Hydrogen-rich saline treatment significantly attenuated lung injury as indicated by significantly improved gas exchange and histological changes in the lung and significantly reduced lung water content (LWC) and neutrophil infiltration 8h after CLP. Lipid peroxidation and DNA oxidation in the lung tissue were significantly reduced along with a decreased nitrotyrosine content and maintained superoxide dismutase activity in the presence of hydrogen, demonstrating antioxidant role of hydrogen in CLP-induced ALI. Importantly, hydrogen-rich saline treatment significantly inhibited the activation of p-p38 and NF-κB while suppressing the production of several proinflammatory mediators. CONCLUSIONS This observation indicated that hydrogen-rich saline peritoneal injection improves histological and functional assessment in rat model of CLP-induced ALI. The therapeutic effects of hydrogen-rich saline may be related to antioxidant and anti-inflammatory actions.
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Affiliation(s)
- Yu Zhai
- Department of basic medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, PR China
| | - Xiaohong Zhou
- Department of basic medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, PR China
| | - Qingchun Dai
- Department of intensive care unit, Cangzhou Central Hospital, Cangzhou 061001, PR China
| | - Yamin Fan
- Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, PR China
| | - Xinli Huang
- Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, PR China.
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Ohta S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods Enzymol 2015; 555:289-317. [PMID: 25747486 DOI: 10.1016/bs.mie.2014.11.038] [Citation(s) in RCA: 112] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Molecular hydrogen (H2) was believed to be inert and nonfunctional in mammalian cells. We overturned this concept by demonstrating that H2 reacts with highly reactive oxidants such as hydroxyl radical ((•)OH) and peroxynitrite (ONOO(-)) inside cells. H2 has several advantages exhibiting marked effects for medical applications: it is mild enough neither to disturb metabolic redox reactions nor to affect signaling by reactive oxygen species. Therefore, it should have no or little adverse effects. H2 can be monitored with an H2-specific electrode or by gas chromatography. H2 rapidly diffuses into tissues and cells to exhibit efficient effects. Thus, we proposed the potential of H2 for preventive and therapeutic applications. There are several methods to ingest or consume H2: inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline onto the eyes. Recent publications revealed that, in addition to the direct neutralization of highly reactive oxidants, H2 indirectly reduces oxidative stress by regulating the expression of various genes. Moreover, by regulating gene expression, H2 functions as an anti-inflammatory, antiallergic, and antiapoptotic molecule, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under way. Since most drugs specifically act on their specific targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has potential for clinical applications for many diseases.
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Affiliation(s)
- Shigeo Ohta
- Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, Kawasaki, Japan.
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Penders J, Kissner R, Koppenol WH. ONOOH does not react with H2: Potential beneficial effects of H2 as an antioxidant by selective reaction with hydroxyl radicals and peroxynitrite. Free Radic Biol Med 2014; 75:191-4. [PMID: 25086438 DOI: 10.1016/j.freeradbiomed.2014.07.025] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 07/17/2014] [Accepted: 07/21/2014] [Indexed: 11/23/2022]
Abstract
H2 has been suggested to act as an antioxidant when administered just before the reperfusion phase of induced oxidative stress. These effects have been reported, for example, for the heart, brain, and liver. It is hypothesized that this beneficial effect may be due to selective scavenging of HO(⋅) and ONOOH by H2. The reaction of H2 with HO(⋅) has been studied by pulse radiolysis in the past and is too slow to be physiologically relevant, not to mention that the reaction yields the reactive H(⋅) radical. We therefore investigated whether H2 reacts with ONOOH and whether the presence of H2 influences the yield of nitration of tyrosine by ONOOH. With only negative results, we entertained the notion that H2 may possibly exert its beneficial effects by reducing Fe(III) centers, oxidized during oxidative stress. However, neither hemes nor iron-sulfur clusters were reduced.
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Affiliation(s)
- Jelle Penders
- Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland; Department of Chemistry and Chemical Engineering, Eindhoven University of Technology, 5612 AZ Eindhoven, The Netherlands
| | - Reinhard Kissner
- Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland
| | - Willem H Koppenol
- Institute of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
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Nour M, Scalzo F, Liebeskind DS. Ischemia-reperfusion injury in stroke. INTERVENTIONAL NEUROLOGY 2014; 1:185-99. [PMID: 25187778 DOI: 10.1159/000353125] [Citation(s) in RCA: 228] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Despite ongoing advances in stroke imaging and treatment, ischemic and hemorrhagic stroke continue to debilitate patients with devastating outcomes at both the personal and societal levels. While the ultimate goal of therapy in ischemic stroke is geared towards restoration of blood flow, even when mitigation of initial tissue hypoxia is successful, exacerbation of tissue injury may occur in the form of cell death, or alternatively, hemorrhagic transformation of reperfused tissue. Animal models have extensively demonstrated the concept of reperfusion injury at the molecular and cellular levels, yet no study has quantified this effect in stroke patients. These preclinical models have also demonstrated the success of a wide array of neuroprotective strategies at lessening the deleterious effects of reperfusion injury. Serial multimodal imaging may provide a framework for developing therapies for reperfusion injury.
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Affiliation(s)
- May Nour
- Departments of Neurology and Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Calif., USA
| | - Fabien Scalzo
- Departments of Neurology and Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Calif., USA
| | - David S Liebeskind
- Departments of Neurology and Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Calif., USA
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Mano Y, Kotani T, Ito M, Nagai T, Ichinohashi Y, Yamada K, Ohno K, Kikkawa F, Toyokuni S. Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion. Free Radic Biol Med 2014; 69:324-30. [PMID: 24509162 DOI: 10.1016/j.freeradbiomed.2014.01.037] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2013] [Revised: 01/25/2014] [Accepted: 01/30/2014] [Indexed: 10/25/2022]
Abstract
Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. Here, we studied the effects of H2 on rat fetal hippocampal damage caused by ischemia and reperfusion (IR) on day 16 of pregnancy with the transient occlusion of the bilateral utero-ovarian arteries. Starting 2 days before the operation, we provided the mothers with hydrogen-saturated water ad libitum until vaginal delivery. We observed a significant increase in the concentration of H2 in the placenta after the oral administration of hydrogen-saturated water to the mothers, with less placental oxidative damage after IR in the presence of H2. Neonatal growth retardation was observed in the IR group, which was alleviated by the H2 administration. We analyzed the neuronal cell damage in the CA1 and CA3 areas of the hippocampus at day 7 after birth by immunohistochemical analysis of the 8-oxo-7,8-dihydro-2׳-deoxyguanosine- and 4-hydroxy-2-nonenal-modified proteins. Both oxidative stress markers were significantly increased in the IR group, which was again ameliorated by the H2 intake. Last, 8-week-old rats were subjected to a Morris water maze test. Maternal H2 administration improved the reference memory of the offspring to the sham level after IR injury during pregnancy. Overall, the present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy.
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Affiliation(s)
- Yukio Mano
- Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Gynecology and Obstetrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Tomomi Kotani
- Department of Gynecology and Obstetrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Mikako Ito
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Taku Nagai
- Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Yuko Ichinohashi
- Department of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya 466-8550, Japan
| | - Kiyofumi Yamada
- Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Kinji Ohno
- Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Fumitaka Kikkawa
- Department of Gynecology and Obstetrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Shinya Toyokuni
- Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
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Lin Y, Zhang W, Qi F, Cui W, Xie Y, Shen W. Hydrogen-rich water regulates cucumber adventitious root development in a heme oxygenase-1/carbon monoxide-dependent manner. JOURNAL OF PLANT PHYSIOLOGY 2014; 171:1-8. [PMID: 24331413 DOI: 10.1016/j.jplph.2013.08.009] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Revised: 07/06/2013] [Accepted: 08/15/2013] [Indexed: 05/08/2023]
Abstract
Hydrogen gas (H2) is an endogenous gaseous molecule in plants. Although its reputation is as a "biologically inert gas", recent results suggested that H2 has therapeutic antioxidant properties in animals and plays fundamental roles in plant responses to environmental stresses. However, whether H2 regulates root morphological patterns is largely unknown. In this report, hydrogen-rich water (HRW) was used to characterize H2 physiological roles and possible signaling transduction pathways in the promotion of adventitious root (AR) formation in cucumber explants. Our results showed that a 50% concentration of HRW was able to mimic the effect of hemin, an inducer of a carbon monoxide (CO) synthetic enzyme, and heme oxygenase-1 (HO-1), in restoring AR formation in comparison with the inhibition effect conferred by auxin-depletion treatment alone. It was further shown that the inducible effect of HRW could be further blocked by the co-treatment with N-1-naphthylphtalamic acid (NPA; an auxin transport inhibitor). The HRW-induced response, at least partially, was HO-1-dependent. This conclusion was supported by the fact that the exposure of cucumber explants to HRW up-regulates cucumber HO-1 gene expression and its protein levels. HRW-mediated induction of representative target genes related to auxin signaling and AR formation, such as CsDNAJ-1, CsCDPK1/5, CsCDC6, CsAUX22B-like, and CsAUX22D-like, and thereafter AR formation (particularly in the AR length) was differentially sensitive to the HO-1 inhibitor zinc protoporphyrin IX (ZnPP). Above blocking actions were clearly reversed by CO, further confirming that the above response was HO-1/CO-specific. However, the addition of a well-known antioxidant, ascorbic acid (AsA), failed to influence AR formation triggered by HRW, thus ruling out the involvement of redox homeostasis in this process. Together, these results indicated that HRW-induced adventitious rooting is, at least partially, correlated with the HO-1/CO-mediated responses. We also suggested that exogenous HRW treatment on plants might be a good option to induce root organogenesis.
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Affiliation(s)
- Yuting Lin
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Wei Zhang
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Fang Qi
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Weiti Cui
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Yanjie Xie
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China
| | - Wenbiao Shen
- College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China.
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Li Q, Kato S, Matsuoka D, Tanaka H, Miwa N. Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Med Gas Res 2013; 3:20. [PMID: 24020833 PMCID: PMC3843550 DOI: 10.1186/2045-9912-3-20] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2013] [Accepted: 09/05/2013] [Indexed: 12/25/2022] Open
Abstract
Background Pressure ulcer (PU) is common in immobile elderly patients, and there are some research works to investigate a preventive and curative method, but not to find sufficient effectiveness. The aim of this study is to clarify the clinical effectiveness on wound healing in patients with PU by hydrogen-dissolved water (HW) intake via tube-feeding (TF). Furthermore, normal human dermal fibroblasts OUMS-36 and normal human epidermis-derived cell line HaCaT keratinocytes were examined in vitro to explore the mechanisms relating to whether hydrogen plays a role in wound-healing at the cellular level. Methods Twenty-two severely hospitalized elderly Japanese patients with PU were recruited in the present study, and their ages ranged from 71.0 to 101.0 (86.7 ± 8.2) years old, 12 male and 10 female patients, all suffering from eating disorder and bedridden syndrome as the secondary results of various underlying diseases. All patients received routine care treatments for PU in combination with HW intake via TF for 600 mL per day, in place of partial moisture replenishment. On the other hand, HW was prepared with a hydrogen-bubbling apparatus which produces HW with 0.8-1.3 ppm of dissolved hydrogen concentration (DH) and −602 mV to −583 mV of oxidation-reduction potential (ORP), in contrast to reversed osmotic ultra-pure water (RW), as the reference, with DH of < 0.018 ppm and ORP of +184 mV for use in the in vitro experimental research. In in vitro experiments, OUMS-36 fibroblasts and HaCaT keratinocytes were respectively cultured in medium prepared with HW and/or RW. Immunostain was used for detecting type-I collagen reconstruction in OUMS-36 cells. And intracellular reactive oxygen species (ROS) were quantified by NBT assay, and cell viability of HaCaT cells was examined by WST-1 assay, respectively. Results Twenty-two patients were retrospectively divided into an effective group (EG, n = 12) and a less effective group (LG, n = 10) according to the outcomes of endpoint evaluation and the healing criteria. PU hospitalized days in EG were significantly shorter than in LG (113.3 days vs. 155.4 days, p < 0.05), and the shortening rate was approximately 28.1%. Either in EG or in LG, the reducing changes (EG: 91.4%; LG: 48.6%) of wound size represented statistically significant difference versus before HW intake (p < 0.05, p < 0.001). The in vitro data demonstrate that intracellular ROS as quantified by NBT assay was diminished by HW, but not by RW, in ultraviolet-A (UVA)-irradiated HaCaT cells. Nuclear condensation and fragmentation had occurred for UVA-irradiated HaCaT cells in RW, but scarcely occurred in HW as demonstrated by Hoechst 33342 staining. Besides, under UVA-irradiation, either the mitochondrial reducing ability of HaCaT cells or the type-I collagen construction in OUMS-36 cells deteriorated in RW-prepared culture medium, but was retained in HW-prepared culture medium as shown by WST-1 assay or immunostain, respectively. Conclusions HW intake via TF was demonstrated, for severely hospitalized elderly patients with PU, to execute wound size reduction and early recovery, which potently ensue from either type-I collagen construction in dermal fibroblasts or the promoted mitochondrial reducing ability and ROS repression in epidermal keratinocytes as shown by immunostain or NBT and WST-1 assays, respectively.
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Affiliation(s)
- Qiang Li
- Department of Radiological Technology, Faculty of Health Sciences, Butsuryo College of Osaka, Otorikitamachi 3-33, Nishi-ku, Sakai, Osaka 593-8328, Japan.
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Shinbo T, Kokubo K, Sato Y, Hagiri S, Hataishi R, Hirose M, Kobayashi H. Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart. Am J Physiol Heart Circ Physiol 2013; 305:H542-50. [DOI: 10.1152/ajpheart.00844.2012] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H2 is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H2 (2%), or NO + H2, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H2 alone. NO inhalation plus H2 reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H2 with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H2. In conclusion, breathing NO + H2 during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H2 gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.
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Affiliation(s)
- Toshihiro Shinbo
- Department of Medical Engineering and Technology, Kitasato University School of Allied Health Sciences
| | - Kenichi Kokubo
- Department of Medical Engineering and Technology, Kitasato University School of Allied Health Sciences
- Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan; and
| | - Yuri Sato
- Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan; and
| | - Shintaro Hagiri
- Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Ryuji Hataishi
- Department of Medicine, Kitasato University School of Medicine, Kanagawa, Japan
| | - Minoru Hirose
- Department of Medical Engineering and Technology, Kitasato University School of Allied Health Sciences
- Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan; and
| | - Hirosuke Kobayashi
- Department of Medical Engineering and Technology, Kitasato University School of Allied Health Sciences
- Kitasato University Graduate School of Medical Sciences, Kanagawa, Japan; and
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Liu GD, Zhang H, Wang L, Han Q, Zhou SF, Liu P. Molecular hydrogen regulates the expression of miR-9, miR-21 and miR-199 in LPS-activated retinal microglia cells. Int J Ophthalmol 2013; 6:280-5. [PMID: 23826519 DOI: 10.3980/j.issn.2222-3959.2013.03.05] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Accepted: 04/20/2013] [Indexed: 01/14/2023] Open
Abstract
AIM To explore the potential mechanism of molecular hydrogen in the regulation of miRNA expression and signal-modulating activities. METHODS Retinal microglia cells were activated by Lipopolysaccharides (LPS) and then treated with hydrogen-saturated medium or normal medium without hydrogen. qRT-PCR was used to detect the expression difference in miR-9, miR-21 and miR-199 between these two groups. Moreover, the expression of LPS-induced signaling proteins, including Myd88, IKK-β, NF-κB, and PDCD4, were detected by Western blotting. RESULTS The results demonstrated a marked down-regulation of miR-9 and miR-21 and up-regulation of miR-199 by hydrogen treatment; the expression of Myd88 and IKK-β was decreased after hydrogen treatment, whereas PDCD4 was increased, and there was no significant change in NF-κB expression. CONCLUSION The results in the present study indicate that miR-9, miR-199 and miR-21 play an important role in the anti-inflammatory regulation of LPS-activated microglia cells by molecular hydrogen, which will help to explain the protective mechanism of molecular hydrogen against inflammatory injury.
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Affiliation(s)
- Guo-Dan Liu
- Department of Ophthalmology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
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Xie Y, Mao Y, Lai D, Zhang W, Shen W. H(2) enhances arabidopsis salt tolerance by manipulating ZAT10/12-mediated antioxidant defence and controlling sodium exclusion. PLoS One 2012. [PMID: 23185443 PMCID: PMC3504229 DOI: 10.1371/journal.pone.0049800] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background The metabolism of hydrogen gas (H2) in bacteria and algae has been extensively studied for the interesting of developing H2-based fuel. Recently, H2 is recognized as a therapeutic antioxidant and activates several signalling pathways in clinical trials. However, underlying physiological roles and mechanisms of H2 in plants as well as its signalling cascade remain unknown. Methodology/Principal Findings In this report, histochemical, molecular, immunological and genetic approaches were applied to characterize the participation of H2 in enhancing Arabidopsis salt tolerance. An increase of endogenous H2 release was observed 6 hr after exposure to 150 mM NaCl. Arabidopsis pretreated with 50% H2-saturated liquid medium, mimicking the induction of endogenous H2 release when subsequently exposed to NaCl, effectively decreased salinity-induced growth inhibition. Further results showed that H2 pretreatment modulated genes/proteins of zinc-finger transcription factor ZAT10/12 and related antioxidant defence enzymes, thus significantly counteracting the NaCl-induced reactive oxygen species (ROS) overproduction and lipid peroxidation. Additionally, H2 pretreatment maintained ion homeostasis by regulating the antiporters and H+ pump responsible for Na+ exclusion (in particular) and compartmentation. Genetic evidence suggested that SOS1 and cAPX1 might be the target genes of H2 signalling. Conclusions Overall, our findings indicate that H2 acts as a novel and cytoprotective regulator in coupling ZAT10/12-mediated antioxidant defence and maintenance of ion homeostasis in the improvement of Arabidopsis salt tolerance.
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Affiliation(s)
- Yanjie Xie
- College of Life Sciences, Co. Laboratory of Nanjing Agricultural University, Nanjing, Jiangsu Province, China
- Carl Zeiss Far East, Nanjing Agricultural University, Nanjing, Jiangsu Province, China
| | - Yu Mao
- College of Life Sciences, Co. Laboratory of Nanjing Agricultural University, Nanjing, Jiangsu Province, China
- Carl Zeiss Far East, Nanjing Agricultural University, Nanjing, Jiangsu Province, China
| | - Diwen Lai
- College of Life Sciences, Co. Laboratory of Nanjing Agricultural University, Nanjing, Jiangsu Province, China
- Carl Zeiss Far East, Nanjing Agricultural University, Nanjing, Jiangsu Province, China
| | - Wei Zhang
- College of Life Sciences, Co. Laboratory of Nanjing Agricultural University, Nanjing, Jiangsu Province, China
- Carl Zeiss Far East, Nanjing Agricultural University, Nanjing, Jiangsu Province, China
| | - Wenbiao Shen
- College of Life Sciences, Co. Laboratory of Nanjing Agricultural University, Nanjing, Jiangsu Province, China
- Carl Zeiss Far East, Nanjing Agricultural University, Nanjing, Jiangsu Province, China
- * E-mail:
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45
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Weyker PD, Webb CAJ, Kiamanesh D, Flynn BC. Lung Ischemia Reperfusion Injury. Semin Cardiothorac Vasc Anesth 2012; 17:28-43. [DOI: 10.1177/1089253212458329] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Lung ischemia reperfusion injury (LIRI) is a pathologic process occurring when oxygen supply to the lung has been compromised followed by a period of reperfusion. The disruption of oxygen supply can occur either via limited blood flow or decreased ventilation termed anoxic ischemia and ventilated ischemia, respectively. When reperfusion occurs, blood flow and oxygen are reintroduced to the ischemic lung parenchyma, facilitating a toxic environment through the creation of reactive oxygen species, activation of the immune and coagulation systems, endothelial dysfunction, and apoptotic cell death. This review will focus on the mechanisms of LIRI, the current supportive treatments used, and the many therapies currently under research for prevention and treatment of LIRI.
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Affiliation(s)
- Paul D. Weyker
- College of Physicians and Surgeons of Columbia Presbyterian Hospital, New York, NY, USA
| | | | - David Kiamanesh
- College of Physicians and Surgeons of Columbia Presbyterian Hospital, New York, NY, USA
| | - Brigid C. Flynn
- College of Physicians and Surgeons of Columbia Presbyterian Hospital, New York, NY, USA
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Abstract
Molecular hydrogen (dihydrogen, H(2)) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (•OH) and peroxynitrite (ONOO-). It has been well-known that ionising radiation (IR) causes oxidative damage and consequent apoptosis mainly due to the production of •OH that follows radiolysis of H(2)O. Our department reported the protective effect of H(2) in irradiated cells and mice for the first time, and this effect is well repeated by us and another laboratory in different experimental animal models. A randomised, placebo-controlled investigation also showed consumption of H(2) can improve the quality of life of patients treated with radiotherapy for liver tumours. These encouraging results suggested that H(2) has a potential as a radioprotective agent with efficacy and non-toxicity.
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Affiliation(s)
- Yunhai Chuai
- Department of Radiation Medicine, Second Military Medical University, Shanghai, China
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Shi P, Sun W, Shi P. A hypothesis on chemical mechanism of the effect of hydrogen. Med Gas Res 2012; 2:17. [PMID: 22721274 PMCID: PMC3583302 DOI: 10.1186/2045-9912-2-17] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 05/23/2012] [Indexed: 11/10/2022] Open
Abstract
Many studies have shown that hydrogen can play important roles on the antioxidant, anti-inflammatory and other protective effects. Ohsawa et al have proved that hydrogen can electively and directly scavenge hydroxyl radical. But this mechanism cannot explain more new experimental results. In this article, the hypothesis, which is inspired by H2 could bind to the metal as a ligand, come up to explain its extensive biology effect: Hydrogen could regulate particular metalloproteins by bonding (M-H2 interaction) it. And then it could affect the metabolization of ROS and signal transduction. Metalloproteins may be ones of the target molecules of H2 action. Metal ions may be appropriate role sites for H2 molecules. The hypothesis pointed out a new direction to clarify its mechanisms.
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Affiliation(s)
- Penghui Shi
- Gansu Key Lab of Crop Improvement & Germplasm Enhancement, Gansu Provincial Key Laboratory of Aridland Crop Sciences, Gansu Agricultural University, Lanzhou 730070, China.,Gansu Agricultural University, Anning District, Lanzhou City, Gansu Province, China
| | - Wancang Sun
- Gansu Key Lab of Crop Improvement & Germplasm Enhancement, Gansu Provincial Key Laboratory of Aridland Crop Sciences, Gansu Agricultural University, Lanzhou 730070, China
| | - Pengzhong Shi
- Inner Mongolia University of Science and Technology, School of Material and Metallurgy, Baotou 014010, China
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Zhuang Z, Zhou ML, You WC, Zhu L, Ma CY, Sun XJ, Shi JX. Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits. BMC Neurosci 2012; 13:47. [PMID: 22587664 PMCID: PMC3436733 DOI: 10.1186/1471-2202-13-47] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2011] [Accepted: 04/10/2012] [Indexed: 12/31/2022] Open
Abstract
Background Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits. Results The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5’-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH + saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious. Conclusion The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.
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Affiliation(s)
- Zong Zhuang
- Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China
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Abstract
In this article, we scientifically evaluate the bio-oxidative procedure known as oxygen-ozone therapy. Research over a decade has established a comprehensive framework for understanding and recommending this type of autohemotherapy in vascular diseases. In contrast, a non-specific immunomodulation therapy, using heavily oxidized and denatured blood, has been recently used in studies involving a total of approximately 3000 patients and has led to 'disappointing' results. Such a treatment appears to be an inappropriate example of the so-called minor autohemotherapy, and its poor outcomes may discourage any further studies. Therefore it appears necessary to clarify that the use of only a minimal ozone dose and a valid experimental protocol is likely to produce beneficial results. Millions of people suffer from chronic limb, brain, and heart ischemia, and such patients may benefit if appropriate ozone therapy could be implemented. Accordingly, we propose the need for a well designed, multicenter, clinical trial to be conducted.
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Affiliation(s)
- Velis Bocci
- Department of Physiology, University of Siena, Siena, Italy.
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Chuai Y, Gao F, Li B, Zhao L, Qian L, Cao F, Wang L, Sun X, Cui J, Cai J. Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochem J 2012; 442:49-56. [PMID: 22077489 DOI: 10.1042/bj20111786] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.
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Affiliation(s)
- Yunhai Chuai
- Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, People's Republic of China
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