Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects

Kishimoto, Yasuaki; Kato, Taichi; Ito, Mikako; Azuma, Yoshiteru; Fukasawa, Yoshie; Ohno, Kinji; Kojima, Seiji

doi:10.1016/j.jtcvs.2015.05.052

Cited by 43 publications

(39 citation statements)

References 33 publications

(39 reference statements)

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“…MCT induces severe PAH and this animal model imitates certain key characteristics of human PAH, including pulmonary vascular remodeling, PASMC proliferation, and oxidative stress [37], [38]. In this study, our data revealed that 4-HNE levels were significantly elevated in the lungs of rats with MCT-induced PAH and that 4-HNE promoted the proliferation and migration of HPASMCs in vitro .…”

Section: Discussionsupporting

confidence: 54%

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension

Liu

et al. 2017

Redox Biology

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The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling. We found that low concentrations of 4-HNE (0.1 and 1 μM) stimulated cell proliferation by enhancing cyclin D1 and c-Myc expression in primary HPASMCs. Low 4-HNE concentrations also enhanced cell migration by activating the nuclear factor kappa B (NF-κB) signaling pathway, thereby regulating matrix metalloprotein (MMP)-9 and MMP2 expression in vitro. In vivo, Alda-1, an ALDH2 agonist, significantly stimulated ALDH2 activity, reducing elevated 4-HNE and malondialdehyde levels and right ventricular systolic pressure in a monocrotaline-induced PAH animal model to the level of control animals. Our findings indicate that 4-HNE plays an important role in the abnormal proliferation and migration of HPASMCs, and that ALDH2 activation can attenuate 4-HNE-induced PASMC proliferation and migration, possibly by regulating NF-κB activation, in turn ameliorating vascular remodeling in PAH. This mechanism might reflect a new molecular target for treating PAH.

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Section: Discussionsupporting

confidence: 54%

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension

Liu

et al. 2017

Redox Biology

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“…Since Ohsawa et al5 reported that hydrogen could be used in antioxidant therapy, numerous studies have confirmed that molecular hydrogen is a medical gas with beneficial effects on oxidative stress, inflammation, apoptosis, lipid metabolism, and signaling pathways 11. Basic studies and clinical studies have demonstrated that hydrogen ameliorates the pathological conditions in numerous human diseases or disease models in animals 111213. In available studies, hydrogen is administered through the oral intake of hydrogen water,14 intravenous infusion of hydrogen-rich saline15 and inhalation of air with 2-4% hydrogen gas 16.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of hydrogen rich water on the intestinal ischemia/reperfusion injury due to intestinal intussusception in a rat model

Chen

Sang

et al. 2017

Med Gas Res

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This study aimed to investigate the protective effects of hydrogen rich water on the intestinal ischemia/reperfusion (I/R) injury in a rat intestinal intussusception (II) model. Ninety Sprague-Dawley rats were randomly assigned into three groups (n = 30 per group). In sham group, rats received laparotomy, and the intestine was exposed for 15 minutes without II. In I/R + saline group and I/R + hydrogen group, rats received II after laparotomy and then intestine was relocated 8 hours later, followed by immediately intraperitoneal injection of normal saline and hydrogen rich water (HRW) (5 mL/kg), respectively. One hour later, the intestine was collected for hematoxylin-eosin staining and immunohistochemistry for apoptotic cells and 8-oxo-deoxyguanosine, and blood was harvested for detection of tumor necrosis factor-α, malondialdehyde and superoxide dismutase. Hematoxylin-eosin staining showed the intestinal mucosa was significantly damaged in I/R + saline group, which was markedly attenuated after HRW treatment. The serum tumor necrosis factor-α content increased significantly in I/R + saline group, but HRW treatment reduced serum tumor necrosis factor-α content as compared to I/R + saline group (P < 0.05). Serum malondialdehyde content and 8-oxo-deoxyguanosine positive cells in the intestine increased dramatically after II, but HRW significantly reduced them in I/R+hydrogen group (P < 0.05). In addition, superoxide dismutase activity reduced markedly and apoptotic cells increased in I/R + saline group as compared to sham group, but they HRW increased superoxide dismutase activity and reduced apoptotic cells significantly in I/R + hydrogen group (P < 0.05). Our results indicate hydrogen rich water is able to attenuate II induced intestinal I/R injury via inhibiting intestinal inflammation, attenuating intestinal/serum oxidative stress and reducing apoptotic intestinal cells.

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“…The effects of hydrogen have also been reported in lung injuries secondary to intestinal ischemia/reperfusion and extensive skin burn . We and others have recently reported that hydrogen is also effective for pulmonary hypertension . The effects of hydrogen have been also reported in perinatal disorders: neonatal cerebral hypoxia; LPS‐induced fetal lung injury; preeclampsia; and perinatal brain injury caused by prenatal inflammation …”

Section: Introductionmentioning

confidence: 91%

Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats

et al. 2016

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Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFα and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. © 2016 Wiley Periodicals, Inc.

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Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects

Abstract: Molecular hydrogen ameliorates MCT-induced PAH in rats by suppressing macrophage accumulation, reducing oxidative stress and modulating the STAT3/NFAT axis.

Cited by 43 publications

References 33 publications

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension

Protective effects of hydrogen rich water on the intestinal ischemia/reperfusion injury due to intestinal intussusception in a rat model

Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats

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