Hydrogen therapy may be an effective and specific novel treatment for Acute Graft‐versus‐host disease (<scp>GVHD</scp>)

Qian, Liren; Shen, Jianliang

doi:10.1111/jcmm.12081

Cited by 13 publications

(8 citation statements)

References 39 publications

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“…H 2 is an effective antioxidant for selectively reducing cytotoxic oxygen radicals and alleviating oxidative stress. 27,28 Our results found that pretreatment with HRS significantly reduced MDA levels, an indicator of oxidative damage, in lung tissue, which verified the antioxidant effect of H 2 in LPS-induced ALI. As AECII cells injury is an important cause of ALI and excessive autophagy activation of AECII cells is a key feature of aggravated ALI.…”

Section: Discussionsupporting

confidence: 75%

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Wang

Zhang

et al. 2019

Exp Biol Med (Maywood)

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Over-activation of autophagy due to increased levels of reactive oxygen species is a key mechanism of lipopolysaccharide-induced acute lung injury. Hydrogen-rich saline, an antioxidant, has been proved to be an effective agent for the prevention of acute lung injury, but the underlying mechanism remains unclear. Here, we investigated the mechanism through which hydrogen-rich saline prevents acute lung injury by focusing on autophagy regulation. The acute lung injury model was induced using lipopolysaccharide both in vivo and in vitro. The activation of autophagy was observed by detecting the expression of autophagy-related proteins using Western blotting. Lung histopathological changes, malondialdehyde content, wet/dry ratio, inflammatory cell count, protein content in bronchoalveolar lavage fluid, and cell viability were measured to evaluate the severity of acute lung injury. Intracellular reactive oxygen species levels were detected using dihydroethidium, which is a reactive oxygen species fluorescent probe. The results showed that the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II/I (LC3II/I ratio) was obviously increased after lipopolysaccharide administration. Pretreatment with hydrogen-rich saline markedly inhibited the expression of Beclin-1 and the LC3II/I ratio; ameliorated lung histopathological changes, malondialdehyde content and wet/dry ratio; and reduced protein content and infiltration of inflammatory cells in bronchoalveolar lavage fluid. These protective effects were also observed by pretreatment with autophagy inhibitor 3-methyladenine. Similar results were found in vitro. The production of reactive oxygen species and the activation of the AMPK/mTOR pathway were notably enhanced in MLE-12 cells after lipopolysaccharide treatment, and ameliorated by the hydrogen-rich medium. The activation of AMPK induced by lipopolysaccharide was also inhibited by pretreatment with N-acetyl-L-cysteine (a reactive oxygen species scavenger). In addition, the over-activation of autophagy was also suppressed by compound C (an AMPK inhibitor). In conclusion, hydrogen-rich saline alleviated lipopolysaccharide-induced acute lung injury by inhibiting excessive autophagy activation via the ROS/AMPK/mTOR pathway in mice. Hydrogen-rich saline may be a new therapeutic strategy for acute lung injury prevention and treatment in the future. Impact statement Acute lung injury (ALI), a common complication of many serious health issues, such as serious infection, burns, and shock, is one of the most common critical illnesses in clinical practice with a high mortality rate of 30–40%. There are still short of effective prevention and treatment measures. Evidence is growing that hydrogen-rich saline (HRS) may be an effective drug for the prevention and treatment of ALI. However, the mechanisms involved in have not been clearly understood. In this study, we investigated the underling mechanisms by focusing on autophagy regulation. The results showed that HRS ameliorated lipopolysaccharide-induced ALI in mice by inhibiting autophagy over-activation through ROS/AMPK/mTOR pathway. HRS may be a new therapeutic strategy for ALI prevention and treatment in the future.

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Section: Discussionsupporting

confidence: 75%

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Wang

Zhang

et al. 2019

Exp Biol Med (Maywood)

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“…Our findings show that hydrogen-rich saline can significantly reduce the grading of tissue histopathology, including skin, liver, and gut. There were no criteria provided in the grading of spleen histopathology in the GVHD model, but some studies have reported that in the GVHD model normal spleen structure disappeared, and the number of lymphocytes in white pulp decreased [ 32 – 37 ]. Our study shows that hydrogen treatment can reduce spleen damage.…”

Section: Discussionmentioning

confidence: 99%

Administration of Hydrogen-Rich Saline in Mice with Allogeneic Hematopoietic Stem-Cell Transplantation

et al. 2015

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BackgroundHydrogen, as a novel antioxidant, has been shown to selectively reduce the level of hydroxyl radicals and alleviate acute oxidative stress in many animal experiments. Hydrogen-rich saline provides a high concentration of hydrogen that can be easily and safely applied. Allogeneic hematopoietic stem-cell transplantation (HSCT) has been the most curative therapy for hematological malignancies. However, acute graft-versus-host disease (aGVHD) is the main cause of death in post-transplantation patients. In this study, we examined whether hydrogen-rich saline would show favorable effects on acute GVHD in mice.Material/MethodsAfter lethal irradiation, BALB/c mice received bone marrow transplantation from C57BL/6 mice. Hydrogen-rich saline (5 ml/kg) was given to recipient mice in the hydrogen group once a day by intraperitoneal injection, and saline (5 ml/kg) was given to recipient mice in the saline group. Survival rates were monitored, clinical and pathological scores of aGVHD were determined after bone marrow transplantation (BMT), and the serum cytokine levels were examined on the 7th day after BMT.ResultThis study proves that hydrogen-rich saline increased the survival rate, reduced clinical and histopathological scores of aGVHD, promoted the recovery of white blood cells, reduced the serum cytokine levels, and reversed tissue damage after transplantation in mice.ConclusionsHydrogen has potential as an effective and safe therapeutic agent in aGVHD.

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“…An interesting potential use of hydrogen is its ability to protect against graft-versus-host disease (GvHD) [230]. Hematopoietic stem cell transplantation has been successfully used for the treatment of certain leukemias and other malignant and non-malignant hematologic diseases [231].…”

Section: Hydrogen Effects On Radiation and Cancer Treatmentmentioning

confidence: 99%

“…However, GvHD is a severe complication that can limit its application. Qian and Shen [230] have proposed that hydrogen therapy be used to reduce ROS/RNS important in the development of GvHD and reduce the levels of inflammatory cytokines that play a role in the development of GvHD.…”

Section: Hydrogen Effects On Radiation and Cancer Treatmentmentioning

confidence: 99%

Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine

Nicolson¹,

Ferreira²,

Settineri³

et al. 2016

IJCM

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Here we review the literature on the effects of molecular hydrogen (H2) on normal human subjects and patients with a variety of diagnoses, such as metabolic, rheumatic, cardiovascular and neurodegenerative and other diseases, infections and physical and radiation damage as well as effects on aging and exercise. Although the effects of H2 have been studied in multiple animal models of human disease, such studies will not be reviewed in depth here. H2 can be administered as a gas, in saline implants or infusions, as topical solutions or baths or by drinking H2-enriched water. This latter method is the easiest and least costly method of administration. There are no safety issues with hydrogen; it has been used for years in gas mixtures for deep diving and in numerous clinical trials without adverse events, and there are no warnings in the literature of its toxicity or longterm exposure effects. Molecular hydrogen has proven useful and convenient as a novel antioxidant and modifier of gene expression in many conditions where oxidative stress and changes in gene expression result in cellular damage.

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Hydrogen therapy may be an effective and specific novel treatment for Acute Graft‐versus‐host disease (GVHD)

Cited by 13 publications

References 39 publications

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

Administration of Hydrogen-Rich Saline in Mice with Allogeneic Hematopoietic Stem-Cell Transplantation

Clinical Effects of Hydrogen Administration: From Animal and Human Diseases to Exercise Medicine

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