scholarly journals Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

2018 ◽  
Vol 46 (6) ◽  
pp. 2434-2444 ◽  
Author(s):  
Yao Zhou ◽  
Weiming He ◽  
Wei Sun ◽  
Zhanwei Zhou ◽  
Minjie Sun ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Protein Oxidation ◽  
High Glucose ◽  
Cell Injury ◽  
Mesothelial Cell ◽  
Oxidative Modification ◽  
Cell Counting ◽  
Dialysis Solution ◽  
Peritoneal Dialysis Solution ◽  
Peritoneal Mesothelial Cell

Background/Aims: Long-term use of high-glucose peritoneal dialysis solution (PDS) induces peritoneal mesothelial cell (PMC) injury, peritoneal dysfunction, and peritoneal dialysis (PD) failure in patients with end-stage renal disease. How to preserve PMCs in PD is a major challenge for nephrologists worldwide. In this study, we aimed to elucidate the efficacy and mechanisms of sulfotanshinone IIA sodium (Tan IIa) in ameliorating high-glucose PDS-induced human PMC injury. Methods: The human PMC line HMrSV5 was incubated with 4.25% PDS in vitro to mimic the high-glucose conditions in PD. Cellular viability was measured by Cell Counting Kit 8. Generation of superoxide and reactive oxygen species (ROS) was assessed using a Total ROS/Superoxide Detection Kit. Oxidative modification of protein was evaluated by OxyBlot Protein Oxidation Detection Kit. TUNEL (dT-mediated dUTP nick end labeling) assay and DAPI (4,6-diamidino-2-phenylindole) staining were used to evaluate apoptosis. Western blot analysis was performed to evaluate the efficacy and mechanisms of Tan IIa. Results: Tan IIa protected PMCs against PDS-induced injury as evidenced by alleviating changes in morphology and loss of cell viability. Consistent with their antioxidant properties, N-acetyl-L-cysteine (NAC) and Tan IIa suppressed superoxide and ROS production, protein oxidation, and apoptosis elicited by PDS. Apoptosis signal-regulating kinase 1 (ASK1)-p38 signaling was activated by PDS. Both Tan IIa and NAC suppressed ASK1 and p38 phosphorylation elicited by PDS. Moreover, genetic downregulation of ASK1 ameliorated cell injury and inhibited the phosphorylation of p38 and activation of caspase 3. Conclusion: Tan IIa protects PMCs against PDS-induced oxidative injury through suppression of ASK1-p38 signaling.

scholarly journals Valsartan ameliorates high glucose-induced peritoneal fibrosis by blocking mTORC1 signaling

2020 ◽  
Vol 245 (11) ◽  
pp. 983-993 ◽  
Author(s):  
Jing Liu ◽  
Yuan Feng ◽  
Cheng Sun ◽  
Wei Zhu ◽  
Qing-Yan Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Peritoneal Dialysis ◽  
Protein Expression ◽  
High Glucose ◽  
Collagen I ◽  
Peritoneal Fibrosis ◽  
Dialysis Solution ◽  
Mtorc1 Pathway ◽  
Peritoneal Dialysis Solution

Our previous study demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated in peritoneal fibrosis under high glucose condition. This study aimed to investigate whether valsartan inhibits high glucose-induced peritoneal fibrosis via decreasing the activity of the mTORC1 pathway. We used high glucose peritoneal dialysis solution in a mouse peritoneal dialysis model to induce peritoneal fibrosis in vivo and high glucose in human peritoneal mesothelial cells (HPMCs) to stimulate extracellular matrix accumulation in vitro. After injections of peritoneal dialysis solution containing 4.25% glucose for four weeks, mice showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expression of extracellular matrix proteins, such as α-smooth muscle actin (α-SMA) and collagen I. Oral gavage of valsartan significantly ameliorated these pathological changes at both week 6 and week 8. These effects of valsartan were closely correlated with a decrease in the activation of the mTORC1 signal, which was mediated by the downregulation of the protein expression of phosphorylated (p)-mTOR, p-eukaryotic initiation factor 4E-binding protein 1, and p-p70 S6 kinase 1. Further research showed that the protein expression of mTORC1 signal was positively correlated with the expression of both α-SMA and collagen I in the peritoneum. In vitro, high glucose increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly inhibited high glucose-induced extracellular matrix accumulation in HPMCs. The effect was also accompanied by a decrease in the activation of the mTORC1 signal. Furthermore, the mTOR agonist MHY1485 reversed the downregulation of extracellular matrix components in HPMCs, even in the presence of valsartan. We conclude that valsartan exerts a protective effect against high glucose-induced peritoneal fibrosis via suppressing the activity of the mTORC1 pathway. Impact statement Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro, HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro. Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro, even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.

scholarly journals Peritoneal Dialysis Solution pH and Ca2+ Concentration Regulate Peritoneal Macrophage and Mesothelial Cell Activation

ASAIO Journal ◽  
1994 ◽  
Vol 40 (1) ◽  
pp. 20-23 ◽  
Author(s):  
Silvia Carozzi ◽  
Pietro Marco Caviglia ◽  
Maria Grazia Nasini ◽  
Claudio Schelotto ◽  
Oscar Santoni ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Macrophage ◽  
Cell Activation ◽  
Mesothelial Cell ◽  
Solution Ph ◽  
Dialysis Solution ◽  
Peritoneal Dialysis Solution

Peritoneal Dialysis Solution pH and Ca2+ Concentration Regulate Peritoneal Macrophage and Mesothelial Cell Activation

ASAIO Journal ◽  
1994 ◽  
Vol 40 (1) ◽  
pp. 20-23
Author(s):  
SILVIA CAROZZI ◽  
PIETRO MARCO CAVIGLIA ◽  
MARIA GRAZIA NASINI ◽  
CLAUDIO SCHELOTTO ◽  
OSCAR SANTONI ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Macrophage ◽  
Cell Activation ◽  
Mesothelial Cell ◽  
Solution Ph ◽  
Dialysis Solution ◽  
Peritoneal Dialysis Solution

Peritoneal Dialysis Solution pH and Ca2+ Concentration Regulate Peritoneal Macrophage and Mesothelial Cell Activation

ASAIO Journal ◽  
1994 ◽  
Vol 40 (SUPPLEMENT 1) ◽  
pp. 20???23
Author(s):  
SILVIA CAROZZI ◽  
PIETRO MARCO CAVIGLIA ◽  
MARIA GRAZIA NASINI ◽  
CLAUDIO SCHELOTTO ◽  
OSCAR SANTONI ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Macrophage ◽  
Cell Activation ◽  
Mesothelial Cell ◽  
Solution Ph ◽  
Dialysis Solution ◽  
Peritoneal Dialysis Solution

Biocompatibility of a Peritoneal Dialysis Solution with Amino Acids: Histological Evaluation in the Rabbit

1998 ◽  
Vol 18 (6) ◽  
pp. 610-619 ◽  
Author(s):  
Guido Garosi ◽  
Enzo Gaggiotti ◽  
Giulio Monaci ◽  
Simone Brardi ◽  
Nicola Di Paolo
Keyword(s):  
Amino Acids ◽  
Peritoneal Dialysis ◽  
High Glucose ◽  
Glucose Solution ◽  
Histological Evaluation ◽  
Transmission Electron ◽  
Dialysis Solution ◽  
Low Glucose ◽  
Peritoneal Dialysis Solution

Objective To determine the biocompatibility of a peritoneal dialysis (PD) solution containing amino acids compared to PD solutions containing glucose. Design The biocompatibility of three dialysis solutions containing 1.1% amino acids, 1.36% glucose, and 3.86% glucose, respectively, was evaluated in vivo in rabbits. Methods After 60 days of PD, peritoneal histological changes in rabbits were investigated by light and transmission electron microscopy. The parameters investigated were: (1) mesothelial damage; (2) submesothelial edema; (3) submesothelial cell infiltration; (4) submesothelial fibrosis; and (5) vascular alterations. Semiquantitative evaluations were performed for all the above alterations; quantitative morphometric evaluation was performed for mesothelial damage (cubic transformation of the mesothelium, areas devoid of mesothelium, submesothelial edema) and thickness of peritoneal arteriole walls. Results (1) Mesothelial damage was practically nonexistent in rabbits dialyzed with the solution containing amino acids, and intermediate and severe with low glucose and high-glucose solutions, respectively. Both controls and rabbits dialyzed with amino acid solution showed flat continuous mesothelium; rabbits dialyzed with low-glucose solution showed cubic continuous mesothelium; and rabbits dialyzed with high-glucose solution showed cubic discontinuous mesothelium. Cytopathic mesothelial effects were slight with the solution containing amino acids and severe with both the low and high-glucose solutions. Duplication and thickening of mesothelial basement membrane were never observed. (2) Submesothelial edema showed a worsening trend from controls to rabbits dialyzed with solution containing amino acids, low glucose, and high glucose. (3) No difference in submesothelial infiltration was found between groups. (4) Submesothelial fibrosis was never observed. (5) Vascular alterations were never observed. Conclusion These results are evidence that PD solution with amino acids is more biocompatible than high and also low-glucose solutions.

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