Hydrogen-Rich Saline Promotes the Recovery of Renal Function after Ischemia/Reperfusion Injury in Rats via Anti-apoptosis and Anti-inflammation

Li, Jie; Zhang, Hong; Liu, Hong; Zhou, Jihong; Cui, Lei; Yuan, Siming; Chu, Xianghua; Pan, Yu

doi:10.3389/fphar.2016.00106

Cited by 62 publications

(43 citation statements)

References 34 publications

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“…In this study, we reveal that H 2 blocks ROS accumulation induced by β-adrenoceptor stimulation both in vitro and in vivo. The inhibitory effects of H 2 on ROS also have been reported in various animal models, such as heart ischemia/reperfusion injury (Zhang et al, 2011; Noda et al, 2013; Shinbo et al, 2013), brain injury (Ohsawa et al, 2007; Liu et al, 2011; Wang et al, 2012), renal injury (Li et al, 2016), chemotherapy-induced ovarian injury (Meng et al, 2015), metabolic syndrome (Song et al, 2013), etc. NADPH oxidase and mitochondria have been proposed as primary sites of ROS generation (Dai et al, 2011a).…”

Section: Discussionmentioning

confidence: 89%

Hydrogen (H2) Inhibits Isoproterenol-Induced Cardiac Hypertrophy via Antioxidative Pathways

Zhang

Long

et al. 2016

Front. Pharmacol.

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Background and Purpose: Hydrogen (H2) has been shown to have a strong antioxidant effect on preventing oxidative stress-related diseases. The goal of the present study is to determine the pharmacodynamics of H2 in a model of isoproterenol (ISO)-induced cardiac hypertrophy.Methods: Mice (C57BL/6J; 8–10 weeks of age) were randomly assigned to four groups: Control group (n = 10), ISO group (n = 12), ISO plus H2 group (n = 12), and H2 group (n = 12). Mice received H2 (1 ml/100g/day, intraperitoneal injection) for 7 days before ISO (0.5 mg/100g/day, subcutaneous injection) infusion, and then received ISO with or without H2 for another 7 days. Then, cardiac function was evaluated by echocardiography. Cardiac hypertrophy was reflected by heart weight/body weight, gross morphology of hearts, and heart sections stained with hematoxylin and eosin, and relative atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels. Cardiac reactive oxygen species (ROS), 3-nitrotyrosine and p67 (phox) levels were analyzed by dihydroethidium staining, immunohistochemistry and Western blotting, respectively. For in vitro study, H9c2 cardiomyocytes were pretreated with H2-rich medium for 30 min, and then treated with ISO (10 μM) for the indicated time. The medium and ISO were re-changed every 24 h. Cardiomyocyte surface areas, relative ANP and BNP mRNA levels, the expression of 3-nitrotyrosine, and the dissipation of mitochondrial membrane potential (MMP) were examined. Moreover, the expression of extracellular signal-regulated kinase1/2 (ERK1/2), p-ERK1/2, p38, p-p38, c-Jun NH2-terminal kinase (JNK), and p-JNK were measured by Western blotting both in vivo and in vitro.Results: Intraperitoneal injection of H2 prevented cardiac hypertrophy and improved cardiac function in ISO-infused mice. H2-rich medium blocked ISO-mediated cardiomyocytes hypertrophy in vitro. H2 blocked the excessive expression of NADPH oxidase and the accumulation of ROS, attenuated the decrease of MMP, and inhibited ROS-sensitive ERK1/2, p38, and JNK signaling pathways.Conclusion: H2 inhibits ISO-induced cardiac/cardiomyocytes hypertrophy both in vivo and in vitro, and improves the impaired left ventricular function. H2 exerts its protective effects partially through blocking ROS-sensitive ERK1/2, p38, and JNK signaling pathways.

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Section: Discussionmentioning

confidence: 89%

Hydrogen (H2) Inhibits Isoproterenol-Induced Cardiac Hypertrophy via Antioxidative Pathways

Zhang

Long

et al. 2016

Front. Pharmacol.

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“…Hydrogen has demonstrated a beneficial effect in all solid organs. Several rodent models have shown a beneficial effect in reducing acute and chronic transplant doi: 10.1111/aor.13118 related ischemic injury (6)(7)(8)(9)(10)(11)(12)(13). Nonetheless, there are few clinically relevant studies examining the effect of hydrogen on acute renal function and ischemia reperfusion injury (IRI).…”

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confidence: 99%

Hydrogen Gas Does Not Ameliorate Renal Ischemia Reperfusion Injury in a Preclinical Model

et al. 2018

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In renal transplantation, ischemia reperfusion injury impairs early graft function and can reduce long term graft survival. Hydrogen has antioxidant and anti-inflammatory properties that can reduce the effects of ischemic injury. The aim of this study was to examine the effects of hydrogen gas administered during reperfusion in a preclinical model of kidney ischemia reperfusion injury. Porcine kidneys underwent 15 min of warm ischemia followed by 22 h of cold ischemia. They were then reperfused for 6 h with whole autologous blood on an ex vivo reperfusion circuit. Paired kidneys were randomized to control (n = 6) (25% oxygen, 5% carbon dioxide, 70% nitrogen) or hydrogen (n = 6) (2% hydrogen, 25% oxygen, 5% carbon dioxide, 68% nitrogen) groups. Tissue, urine, and blood samples were collected at baseline and hourly throughout the reperfusion period. Baseline measurements were similar across groups. Following perfusion, there was no significant difference between control and hydrogen groups in urine output (693 mL vs. 608 mL, P = 0.86), renal blood flow (105.9 vs. 108 mL/min/100g, P = 0.89), acid-base homeostasis, or creatinine clearance. There was a significant increase in cytokine levels from baseline to 6 h in both groups (IL-1β P = 0.002; IL-6 P = 0.004; IL-8 P = 0.002). However, there were no significant differences in levels of inflammatory cytokines (IL1β, IL-6, and IL-8) between the groups. The administration of hydrogen gas did not improve renal function, reduce oxidative damage, or inflammation during the reperfusion of ischemically damaged kidneys.

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“…HRS can easily enter cells, become involved in metabolism, and thereby promote cell detoxification, increase cell hydration, and enhance the body’s immune system [13, 14]. Li et al [15] investigated effects of HRS on prevention of renal injury induced by ischemia/reperfusion. The results show that after ischemia/reperfusion injury, levels of BUN, Cr, Bcl-2, caspase-3, caspase-9, caspase-8, IL-6, and TNF-α significantly increased, while Bax expression decreased.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats

Chen¹,

Wang²,

Diao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cardiopulmonary bypass (CPB) is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS) can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. Methods: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB) was used to assess permeability of the blood-brain barrier (BBB); HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT –PCR analyses of brain tissue and neurons. Results: After CPB, brain tissue anatomy was disordered, and cell structure was abnormal. Brain tissue EB content increased. There was an increase in the number of apoptotic cells, an increase in expression of Bax and caspase-3, a decrease in expression of Bcl2, and increases in levels of Akt, GSK3β, P-Akt, and P-GSK3β in brain tissue. HRS treatment attenuated the inflammatory reaction ,brain tissue EB content was significantly reduced and significantly decreased expression levels of Bax, caspase-3, Akt, GSK3β, P-Akt, and P-GSK3β in the brain. After adding the PI3K signaling pathway inhibitor, LY294002, to rat cerebral microvascular endothelial cells (CMECs), HRS could reduce activated Akt expression and downstream regulatory gene phosphorylation of GSK3β expression, and inhibit CMEC apoptosis. Conclusion: The PI3K/Akt/GSK3β signaling pathway plays an important role in the mechanism of CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit CMEC apoptosis through the PI3K/Akt/GSK3β signaling pathway.

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Hydrogen-Rich Saline Promotes the Recovery of Renal Function after Ischemia/Reperfusion Injury in Rats via Anti-apoptosis and Anti-inflammation

Cited by 62 publications

References 34 publications

Hydrogen (H2) Inhibits Isoproterenol-Induced Cardiac Hypertrophy via Antioxidative Pathways

Hydrogen (H2) Inhibits Isoproterenol-Induced Cardiac Hypertrophy via Antioxidative Pathways

Hydrogen Gas Does Not Ameliorate Renal Ischemia Reperfusion Injury in a Preclinical Model

Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats

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