Hydrogen-Rich Saline Attenuates Acute Kidney Injury After Liver Transplantation via Activating p53-Mediated Autophagy

Du, Hongyin; Sheng, Mingwei; Wu, Li; Zhang, Yamin; Shi, Dongxia; Weng, Yiqi; Xu, Rubin; Yu, Wenli

doi:10.1097/tp.0000000000001052

Cited by 41 publications

(41 citation statements)

References 38 publications

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“…Its diffusion to cellular organelles helps to effectively target intracellular inflammatory factors. Previous studies showed that the inhalation of H 2 exerts protective effects on brain, liver, heart, and intestinal I/R injuries ( Bali et al, 2015 ; Malik and Ferguson, 2015 ; Du et al, 2016 ; Nagpure and Bian, 2016 ). Moreover, H 2 acts as an anti-inflammatory agent in acute pancreatitis, colon inflammation and liver inflammation ( Cheng et al, 2014 ; Yemm et al, 2015 ; Han et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2016

Front. Pharmacol.

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Purpose: Hydrogen is a proven novel antioxidant that selectively reduces hydroxyl radicals. In this study, we investigated the effects of hydrogen-rich saline solution on the prevention of renal injury induced by ischemia/reperfusion (I/R) and on renal function recovery.Methods: A rat model of renal I/R injury was induced by 45 min occlusion of the left renal pedicle, followed by 108 h reperfusion. The right kidney was surgically removed. Then, 0.9% NaCl solution (1 ml/kg) or hydrogen-rich saline solution (HRSS; 1 ml/kg) was injected into the abdominal cavity at 4 h intervals. We assessed the influence of HRSS or control saline solution on the recovery of renal function after I/R injury. Kidney tissues were taken at different time points (24, 36, 48, 72, and 108 h after reperfusion) and frozen (-80°C). Kidney cell apoptosis was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive staining. Additionally, the apoptotic factors (Bcl-2, Bax, caspase-3, caspase-9, and caspase-8) and the pro-inflammatory cytokines (IL-6 and TNF-α) were measured in the kidney tissues. Finally, serum blood urea nitrogen (BUN) and creatinine (Cr) levels were measured.Results: Histological analyses revealed a marked reduction of interstitial congestion, edema and hemorrhage in renal tissue after HRSS treatment compared to saline treatment. After I/R injury, BUN, Cr, Bcl-2, caspase-3, caspase-9, caspase-8, IL-6, and TNF-α were all significantly increased, while Bax expression was decreased. HRSS remarkably reversed these changes. Moreover, BUN and Cr decreased more rapidly in the rats treated with HRSS compared to the rats treated with control saline solution.Conclusions: HRSS showed a protective effect in the prevention of renal injury and could promote renal function recovery after I/R injury in rats. HRSS might partially exert its role through an anti-apoptotic and anti-inflammatory action in kidney cells.

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Section: Introductionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2016

Front. Pharmacol.

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“…Chronic hydrogen-rich saline treatment depressed pro-inflammatory cytokines expression, including IL-6 and IL-1β ( 28 ). In addition, hydrogen-rich saline mediates neuroprotection and attenuates acute kidney injury through the regulation of autophagy ( 29 , 30 ). Oral treatment with hydrogen-rich water for 6 months alleviated the progression of AS in apolipoprotein E-knockout mice ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen attenuated oxidized low‑density lipoprotein‑induced inflammation through the stimulation of autophagy via sirtuin 1

Yang

et al. 2018

Exp Ther Med

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Chronic inflammation is a central pathogenic mechanism underlying the induction and progression of atherosclerosis (AS). Hydrogen has been demonstrated to serve a protective role in diverse models of disease. However, the potential effects and mechanism of hydrogen with respect to ox-LDL-induced inflammation have not yet been completely elucidated. In the present study, various concentrations (0, 50 and 100 mg/l) of oxidized low-density lipoprotein (ox-LDL) were used to treat RAW264.7 cells. A Cell Counting kit-8 assay was used to determine cell viability and western blot analysis was performed to determine the expression of proteins that are involved in autophagy. The expression of inflammatory cytokines in ox-LDL-treated macrophages was detected using ELISA. Small interfering (si)RNA against sirtuin 1 (SIRT1) was employed to investigate the mechanism underlying hydrogen-activated autophagy. The results indicated that ox-LDL stimulation promoted inflammatory cytokine expression and impaired autophagic flux in RAW264.7 cells. Furthermore, hydrogen inhibited ox-LDL-induced inflammatory cytokine expression by upregulating autophagic flux. SIRT1 mediated the upregulation of autophagic flux via hydrogen in ox-LDL-treated macrophages. To conclude, the present study provided novel insights into the role of defective autophagy in the pathogenesis of AS and identified autophagy to be a promising therapeutic target for the treatment of AS. Notably, hydrogen may represent a potential agent for the treatment of AS.

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“…Since the first report in 2007, accumulating evidence has demonstrated its therapeutic potential against IRI and the underlying mechanisms therein. Currently, H 2 is known to have 3 definitive effects: antioxidant, anti‐inflammatory, and antiapoptosis . Though some experimental animal studies have shown its therapeutic potential in organ preservation, eg, lung, heart, kidney, intestine, and liver, its clinical use is yet to be applied because of its unfavorable features.…”

mentioning

confidence: 99%

“…Currently, H 2 i s known to have 3 definitive effects: antioxidant, (5)(6)(7)(8)(9)(10)(11)(12)(13) anti-inflammatory, (10,(14)(15)(16) and antiapoptosis. (8,17) Though some experimental animal studies have shown its therapeutic potential in organ preservation, eg, lung, (11) heart, (18) kidney, (6) intestine, (7) and liver, (19,20) its clinical use is yet to be applied because of its unfavorable features.…”

mentioning

confidence: 99%

Hydrogen Flush After Cold Storage as a New End‐Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury

Tamaki¹,

Hata²,

Okamura³

et al. 2018

Liver Transpl

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Cold storage (CS) remains the gold standard for organ preservation worldwide, although it is inevitably associated with ischemia/reperfusion injury (IRI). Molecular hydrogen (H ) is well known to have antioxidative properties. However, its unfavorable features, ie, inflammability, low solubility, and high tissue/substance permeability, have hampered its clinical application. To overcome such obstacles, we developed a novel reconditioning method for donor organs named hydrogen flush after cold storage (HyFACS), which is just an end-ischemic H flush directly to donor organs ex vivo, and, herein, we report its therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV + HA). Functional integrity and morphological damages were then evaluated by 2-hour oxygenated reperfusion at 37°C. HyFACS significantly lowered portal venous pressure, transaminase, and high mobility group box protein 1 release compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was significantly higher in the HyFACS-PV and -PV + HA groups when compared with the others (P < 0.01), demonstrating the efficacy of the PV route to maintain the sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P < 0.01), representing the superiority of the arterial route to attenuate biliary damage. Electron microscopy consistently revealed that sinusoidal ultrastructures were well maintained by portal HyFACS, while microvilli in bile canaliculi were well preserved by arterial flush. As an underlying mechanism, HyFACS significantly lowered oxidative damages, thus improving the glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS significantly protected liver grafts from IRI by ameliorating oxidative damage upon reperfusion in the characteristic manner with its route of administration. Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be a novel pretransplant conditioning for cold-stored donor organs.

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Hydrogen-Rich Saline Attenuates Acute Kidney Injury After Liver Transplantation via Activating p53-Mediated Autophagy

Abstract: HRS is able to protect against AKI after liver transplantation partly by reducing apoptosis, which is possibly involved in the modulation of p53-mediated autophagy.

Cited by 41 publications

References 38 publications

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

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

Hydrogen attenuated oxidized low‑density lipoprotein‑induced inflammation through the stimulation of autophagy via sirtuin 1

Hydrogen Flush After Cold Storage as a New End‐Ischemic Ex Vivo Treatment for Liver Grafts Against Ischemia/Reperfusion Injury

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