Therapeutic effects of hydrogen on chronic graft‐versus‐host disease

Qian, Liren; Liu, Xiaopeng; Shen, Jianliang; Zhao, Delong; Yin, Wu

doi:10.1111/jcmm.13155

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…This feature is adapted to the long-term, repeated, and prolonged disease characteristics of cGVHD, which makes hydrogen-rich water very suitable for cGVHD. Previously, we have demonstrated that the survival rate of another cGVHD mice model was increased by intraperitoneally injecting hydrogen-rich saline, and the pathological changes in skin was also improved [27]. In this study, we used oral hydrogen-rich water, which is more convenient than hydrogen-rich saline for injection and inhalation of hydrogen gas.…”

Section: Discussionmentioning

confidence: 99%

“…About 2 cm 2 shaved skin from interscapular region was selected. The hematoxylin and eosin (HE) staining was performed as we previously described [27]. A dermatologist, blinded to the groups of animals, scored from five aspects: epidermal structural changes, inflammatory cell infiltration, reduction or loss of hair follicles, dermal fibrosis, and reduction or loss of fat.…”

Section: Evaluation Of Cgvhdmentioning

confidence: 99%

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Hydrogen‐Rich Water Ameliorates Murine Chronic Graft‐versus‐Host Disease through Antioxidation

Qian

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for various hematopoietic diseases and certain hereditary diseases. Chronic graft-versus-host disease (cGVHD) has become the main life-threatening complication and cause of death in later stage postallo-HSCT. Current treatment options for cGVHD are limited. Hydrogen gas (H2) has been demonstrated that has antioxidative, anti-inflammatory, and antifibrosis effects. The aim of this study was to confirm whether oral administration hydrogen-rich water exerted therapeutic effects on a scleroderma cGVHD mouse model and tried to explain the mechanism underly it. Methods. A mouse cGVHD model was established by haploidentical bone marrow transplantation. To evaluate therapeutic effects of H2 on cGVHD, survival rate, changes in clinical scores, and skin pathologic characteristics of cGVHD mice were observed. To evaluate its therapeutic mechanism, we detected the expression levels of antioxidative enzymes heme oxygenase-1(HO-1) and NAD (P)H: quinone acceptor oxidoreductase 1(NQO1) in skin homogenates. We also detected the expression level of the apoptotic protein caspase-3 in skin homogenates. Results. 1-month survival rate of cGVHD mice in the hydrogen group reached 93.3%, significantly higher than 66.7% in the nonhydrogen group ( p < 0.05 ). Clinical score of cGVHD mice was improved by hydrogen-rich water at 96 days posttransplantation (2.2 versus 4.5, p < 0.05 ). The skin pathological condition of cGVHD mice was significantly improved by hydrogen-rich water. At 96 days posttransplantation, average skin pathological hematoxylin and eosin (HE) staining score in the hydrogen group was 1.05, which was significantly lower than 3.2 in the nonhydrogen group ( p < 0.01 ). Average Masson staining score was 0.6 point in the hydrogen group, lower than 0.9 point in the nonhydrogen group ( p < 0.05 ). Both the relative expression levels of HO-1 and NQO1 proteins in skin specimens of cGVHD mice in the hydrogen group were lower than that in the nonhydrogen group (2.47 versus 6.21 and 1.83 versus 3.59, p < 0.05 ). The relative expression level of caspase-3 protein in skin specimens of cGVHD mice increased to 7.17 on the 96th day after transplantation, significantly higher than 4.36 in the hydrogen group. Conclusion. In this study, we found that oral hydrogen-rich water improved the survival rate and clinical symptoms of cGVHD mice by antioxidant and antiapoptosis. This study would pave the way for further clinical study, which may provide a new treatment option for cGVHD.

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Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of Cgvhdmentioning

confidence: 99%

Hydrogen‐Rich Water Ameliorates Murine Chronic Graft‐versus‐Host Disease through Antioxidation

Qian

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Since H 2 has anti-inflammatory and anti-fibrosis effects, we speculate that H 2 may have potential therapeutic effects for cGVHD after allo-HSCT. We have proved the its therapeutic effects in a mouse model preliminary ( 15 ). To further verify the hypothesis, we conducted a multiple center study of hydrogen in patients with corticosteroid-refractory/dependent cGVHD to look at response rate and to detect any unique toxicities.…”

Section: Introductionmentioning

confidence: 89%

Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial

et al. 2020

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Chronic graft-versus-host-disease (cGVHD) is the leading cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation(HSCT). There is no standard therapy for patients refractory or dependent to corticosteroid treatment. We hypothesized that hydrogen may exert therapeutic effects on cGVHD patients with few side effects. A prospective open-label phase 2 study of hydrogen was conducted. Patients received hydrogen-rich water 4ml/kg orally three times a day. Responses were graded in the skin, mouth, Gastrointestinal(GI), liver, eyes, lungs and joints and fascia every 3 months. A total of 24 patients (median age 27) were enrolled. Of the 24 patients, 18 (75%; 95% CI, 55.1% to 88%) had an objective response. No significant toxicity was observed. The estimated 4-year overall survival rate was 74.7%(95% CI, 54.9%–94.5%). The survival time was significantly prolonged in the response group. The survival rate at 4 years in the response group is significantly higher than the nonresponse group (86.6% vs 0%; p= 0.000132). Hydrogen showed great efficacy on cGVHD patients and long-term administration of hydrogen was not associated with significant toxic effects. The trial was registered at www.ClinicalTrials.Gov, NCT02918188.

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“…Due to the anti-inflammatory and antifibrosis effects of hydrogen, we hypothesized that it may have therapeutic effects on chronic GVHD. In our study, survival rate of chronic GVHD mice was increased and the skin lesions were reduced by hydrogen [18]. Besides, we also published a case report of a patient with severe chronic graft-versus-host disease successfully treated by drinking hydrogen-rich water which makes hydrogen as a promising method for treating GVHD [19].…”

Section: Graft-versus-host Disease (Gvhd)mentioning

confidence: 99%

Medical Application of Hydrogen in Hematological Diseases

Qian

Cen

et al. 2019

Oxidative Medicine and Cellular Longevity

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Hydrogen gas has been reported to have medical efficacy since the 1880s. Still, medical researchers did not pay much attention to hydrogen gas until the 20th century. Recent research, both basic and clinical, has proven that hydrogen is an important physiological regulatory factor with antioxidative, anti-inflammatory, and antiapoptotic effects. In the past two decades, more than 1000 papers have been published on the topic, including organ ischemia-reperfusion injury, radiation injury, diabetes, atherosclerosis, hypertension, or cancer. We have previously hypothesized and proven the therapeutic effects of hydrogen gas in graft-versus-host disease following stem cell transplantation. In the current manuscript, we present the clinical advances of hydrogen gas in hematological disorders.

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Therapeutic effects of hydrogen on chronic graft‐versus‐host disease

Cited by 6 publications

References 24 publications

Hydrogen‐Rich Water Ameliorates Murine Chronic Graft‐versus‐Host Disease through Antioxidation

Hydrogen‐Rich Water Ameliorates Murine Chronic Graft‐versus‐Host Disease through Antioxidation

Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial

Medical Application of Hydrogen in Hematological Diseases

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