Hydrogen Sulfide Ameliorates High-Glucose Toxicity in Rat Peritoneal Mesothelial Cells by Attenuating Oxidative Stress

Lu, Ying; Shen, Huaying; Shi, Xiaosong; Feng, Sheng; Zhi, Wang; Shi, Yuanming

doi:10.1159/000358436

Cited by 8 publications

(6 citation statements)

References 47 publications

(26 reference statements)

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“…We suppose that high glucose may, at least partly, play a crucial role as an oxidant, as reported elsewhere [ 11 – 13 ], which indicates room for improvement in the biocompatibility of the present standard solutions. Studies on clinical approaches to peritoneal protection have been limited so far [ 25 – 27 ].…”

Section: Discussionmentioning

confidence: 99%

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

et al. 2017

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BackgroundPeritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H2) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H2 on the peritoneal membrane of experimental PD rats.MethodEight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8–11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H2PD group (PD solution with dissolved H2 at 400 ppb). Furthermore, the influence of iron (FeCl3: 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H2PD groups). The H2PD solution was manufactured by bathing a PD bag in H2-oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis.ResultsIn the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H2PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H2PD group.ConclusionH2-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

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Section: Discussionmentioning

confidence: 99%

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

et al. 2017

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“…However, the benefits of PD are short lived due to the gradual loss of peritoneal function caused by high-glucose PDFs and frequent peritonitis [14,15]. In the present study, the rat model of peritoneal fibrosis was established by intraperitoneal injection of 4.25%-glucose PDFs and LPS.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Alleviates Peritoneal Fibrosis via Attenuating Inflammation and TGF-β1 Synthesis

Lu¹,

Gao²,

et al. 2015

Nephron

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Background/Aims: Peritoneal fibrosis is one of the long-term complications in peritoneal dialysis (PD) patients. Recent evidences have suggested that hydrogen sulfide (H₂S) is beneficial in treating various fibrotic diseases, including pulmonary fibrosis, cirrhosis, kidney fibrosis and cardiac hypertrophy. However, no information is known about the effect of H₂S on peritoneal fibrosis. In the present study, we investigated the effect of H₂S on peritoneal fibrosis and explored its potential mechanisms. Methods: We developed a model of peritoneal fibrosis by intraperitoneally injecting 4.25%-glucose PD fluids and lipopolysaccharide to Sprague-Dawley rats. The rats received daily intraperitoneal injections of NaHS (56 μg/kg), an H₂S donor. After 28 days, the peritoneal equilibration test (PET) was used to assess peritoneal function. At the end of dialysis, the rats were killed and parietal peritoneum was harvested for microscopic examination and immunohistochemistry. Results: On the 28th day, the parietal peritoneum of the PD rats markedly thickened as a result of increased depositions of type III collagen and fibronectin. Moreover, the number of ED-1-positive cells and the expressions of monocyte chemoattractant protein-1, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin and CD31 were significantly increased in the fibrotic peritoneum. Administration of NaHS markedly decreased the biomarkers of inflammation, fibrosis and angiogenesis in the peritoneum. NaHS also improved peritoneal function assessed by PET. Conclusion: Exogenous H₂S ameliorates the pathologic process of peritonitis via attenuating inflammatory events and TGF-β1 synthesis. These results suggest that H₂S may be a potential therapy against peritoneal fibrosis during chronic PD. In the future, compounds releasing H₂S at controlled rate will be assessed as potential candidates to treat peritoneal fibrosis.

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“…26 A previous study confirmed that EMT of PMCs is generally regarded to be the result of oxidative stress; while, antioxidants effectively reverse the EMT in PMCs. 27 In fact, oxidative stress has also been proposed to play a major role in the development of peritoneal deterioration 28 and apoptosis. 29 Among Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ligustrazine on rat peritoneal mesothelial cells treated with lipopolysaccharide

Zhang

et al. 2016

Renal Failure

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The apoptosis of peritoneal mesothelial cells (PMCs) and peritoneal fibrosis may induce failure of peritoneal membrane function. The study explored the changes of apoptosis and fibrosis in PMCs under lipopolysaccharides (LPS) culture and investigated whether Ligustrazine can affect LPSinduced apoptosis and fibrosis. We found that exposure of rat PMCs to 5 mgÁL À1 LPS for 24 h resulted in a significant induction of apoptosis and increased levels in Reactive oxygen species, and caspase-3 activity. Fibronectin, Collagen I, p-p38, and matrix metalloprotein-9 (MMP-9) levels were also significantly increased by LPS. But superoxide dismutase levels were remarkably decreased. Ligustrazine can restore the changes induced by LPS. The protective effect of Ligustrazine on LPS-induced apoptosis and fibrosis may act through inhibition of oxidative stress and p38/MAPKS, ROS/MMP-9 activation in PMCs.ARTICLE HISTORY

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Hydrogen Sulfide Ameliorates High-Glucose Toxicity in Rat Peritoneal Mesothelial Cells by Attenuating Oxidative Stress

Cited by 8 publications

References 47 publications

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

Hydrogen Sulfide Alleviates Peritoneal Fibrosis via Attenuating Inflammation and TGF-β1 Synthesis

Effect of Ligustrazine on rat peritoneal mesothelial cells treated with lipopolysaccharide

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