Oral hydrogen water prevents chronic allograft nephropathy in rats

Cardinal, Jon; Zhan, Jianghua; Wang, Yinna; Sugimoto, Ryujiro; Tsung, Allan; McCurry, Kenneth R.; Billiar, Timothy R.; Nakao, Atsunori

doi:10.1038/ki.2009.421

Cited by 160 publications

(147 citation statements)

References 44 publications

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“…12,17) While there are several methods to deliver H 2 into the body including inhalation of H 2 gas, 18) injection of hydrogensaturated saline, 19) and drinking hydrogen water, 20) we utilized HW produced by electrolysis wherein H 2 was highly dissolved in PW passing through the hydraulic system of the generator, thereby producing characteristics such as neutral pH, extremely low ORP, and high DH.…”

Section: Discussionmentioning

confidence: 99%

Positive Effects of Hydrogen Water on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in NC/Nga Mice

Yoon

Sajo

Ignacio

et al. 2014

Biological & Pharmaceutical Bulletin

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Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. In the present study, we investigated the effect of drinking hydrogen water (HW) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in NC/Nga mice and found that HW ameliorated DNCB-induced AD-like clinical symptoms. In line with this, the level of reactive oxygen species in the HW group was significantly inhibited compared with that in the purified water (PW) group. In parallel, HW enhanced glutathione peroxidase activity in DNCBinduced AD as compared with the PW group. Accordingly, the levels of thymus and activation-regulated chemokine and cytokines were significantly decreased in the HW group compared with the PW group. Notably, the levels of Th 2 cytokine, interleukin-5 (IL-5), and proinflammatory cytokines such as tumor necrosis factor-α and IL-6 in HW-fed mice were significantly lower than in control and PW-fed mice. The total serum immunoglobulin E level was also markedly reduced in the HW group. The collective results indicate that HW suppresses DNCB-induced AD in NC/Nga mice via redox balance and immune modulation and could be a safe clinical fluid treatment for AD.Key words hydrogen water; atopic dermatitis; oxidative stress; immune modulation Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation.1,2) AD is characterized by an impairment of the skinbarrier function, increased oxidative stress, and dysfunctional immune system. Intense infiltration of inflammatory cells release bioactive substance such as cytokines, chemokines, and reactive oxygen species (ROS).3) Of these AD's etiologic factors, inflammatory cytokines are known to regulate skin barrier, thereby aggravating the eczematous reaction in AD. 4)Most acute skin lesions in AD are exhibited by Th 2 inflammatory cytokines, whereas the chronic phase is characterized by Th 1 immune responses.5) The imbalance of cytokine network would play a critical role in the development of AD. 6,7)Together, oxidative stress such as increased ROS and lipid peroxidation is evident in any stage of AD. [8][9][10] An imbalance between ROS and antioxidants can lead to an elevated oxidative stress level. 11)Hydrogen molecule (H 2 ) has been widely used in medical applications as a safe and effective antioxidant and immunomodulator with minimal side effects.12-15) Unlike other antioxidants, which are unable to target organelles, H 2 can penetrate biomembranes and diffuse into the cytosol, mitochondria and nucleus. 13) Moreover, H 2 has been reported to have •OHscavenging activity in culture medium.14) Oral administration of hydrogen water (HW), inhalation of hydrogen gas, and injecting H 2 -dissolved saline is widely accepted to incorporate H 2 in the body. Recently, we reported that HW is effective in house mite-induced dermatitis via immunomodulation. 15) However, this study has a limitation owing to the lack of th...

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Section: Discussionmentioning

confidence: 99%

Positive Effects of Hydrogen Water on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in NC/Nga Mice

Yoon

Sajo

Ignacio

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Therefore, the results suggest that the protective roles of H 2 treatment may be associated with reduced SGN apoptosis. In addition, H 2 treatment can reduce the levels of oxidative products and inflammatory cytokines, as well as increase antioxidant enzymatic activities in many diseases [4,6,[8][9][10][11][12][13][14] . Further studies are needed to determine whether these mechanisms contribute to the protective effects of H 2 treatment against AN.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, many studies, including ours, have found that H 2 has therapeutic roles in many diseases via its ability to reduce oxidative stress, inflammation and apoptosis; these diseases include cerebral damage, spinal cord injury, sepsis, multiple organ dysfunction, chronic allograft nephropathy, tumors and type 2 diabetes [4][5][6][7][8][9][10][11][12][13][14] . Furthermore, H 2 can effectively protect against the morphological and functional cochlear hair cell damage induced by ROS [15] .…”

Section: Introductionmentioning

confidence: 97%

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Xie

et al. 2012

Acta Pharmacol Sin

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Aim: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H 2 ), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. Methods: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H 2 treatment was given twice by exposing the animals to H 2 (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. Results: Treatment with H 2 (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H 2 treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H 2 (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H 2 treatment. However, ouabain did not change the morphology of cochlear hair cells. Conclusion:The results demonstrate that H 2 treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H 2 might be a potential agent for treating hearing impairment in AN patients.

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“…Our laboratory has extensively explored the application of hydrogen for the treatment of various diseases (7,9,33), including acute lung injuries (15,23,24). Hydrogen is a selective radical scavenger for hydroxyl radicals and peroxynitrite (14,37), and this aspect of hydrogen's chemistry may explain its therapeutic effects.…”

Section: L651mentioning

confidence: 99%

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

Kawamura

Wakabayashi

Shigemura

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.

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Oral hydrogen water prevents chronic allograft nephropathy in rats

Cited by 160 publications

References 44 publications

Positive Effects of Hydrogen Water on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in NC/Nga Mice

Positive Effects of Hydrogen Water on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in NC/Nga Mice

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

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