Atorvastatin Reduces High Glucose Toxicity in Rat Peritoneal Mesothelial Cells

Carrión, Blanca; Pérez-Martínez, Francisco C.; Monteagudo, S.; Posadas, Inmaculada; Gómez-Roldán, Carmen; Ceña, Valentı́n; Pérez-Martínez, Juan

doi:10.3747/pdi.2010.00164

Cited by 8 publications

(4 citation statements)

References 49 publications

(55 reference statements)

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“…Nevertheless, the benefits of PD are short-lived, due mainly to morphological and functional alterations of the peritoneum caused by HG PDFs. There is substantial evidence to support HG PDFs cause deterioration of the peritoneum, including an increase in oxidative stress injury and apoptosis in PMCs [11,12]. In this study, it is demonstrated that HG PDFs induce rat PMCs apoptosis.…”

Section: Discussionmentioning

confidence: 61%

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

Lu¹,

Shen²,

Shi³

et al. 2014

Nephron Exp Nephrol

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Background/Aims: Continuous exposure of the peritoneal membrane to high-glucose (HG) peritoneal dialysis fluids (PDFs) can produce peritoneal mesothelial cells (PMCs) injury. It has been demonstrated that hydrogen sulfide (H₂S), the third endogenous gaseous mediator identified after nitric oxide and carbon monoxide, exhibits a potent protective effect on cell activity. We studied the toxic effects of HG PDFs and their reversal by H₂S on cultures of rat PMCs. Methods: Synchronized confluent rat PMCs were incubated with 2.5% glucose PDFs with or without NaHS, an H₂S donor. Cell viability was assessed by methyl thiazolyl tetrazolium assay and flow cytometry. The level of phospho-p38 mitogen-activated protein kinase (MAPK) was analyzed by immunoblotting. p53, Bax and Bcl-2 mRNA expressions by rat PMCs were detected by real-time PCR. The levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and caspase-3 activity were measured. Results: Exposure of rat PMCs to 2.5% glucose PDFs for 24 h resulted in a significant induction of apoptosis, which was attenuated by NaHS. NaHS also restored the 2.5% glucose PDF-induced increase in phospho-p38 MAPK (indices of cellular toxicity). Further investigation of the apoptotic mechanisms in rat PMCs demonstrated that HG activated caspase-3 and upregulated Bax, while it downregulated Bcl-2. All the above responses were prevented by pretreatment with NaHS. Moreover, NaHS reversed the 2.5% glucose PDF-induced increase in ROS generation and decrease in SOD activity. Conclusions: These findings suggest that HG PDFs significantly inhibit rat PMC viability, leading to peritoneal injury. H₂S exhibits a potent anti-apoptotic ability by attenuating oxidative stress and inhibiting caspase-3 activation, which in turn restores peritoneal injury.

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Section: Discussionmentioning

confidence: 61%

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

Lu¹,

Shen²,

Shi³

et al. 2014

Nephron Exp Nephrol

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“…Rat PMCs were isolated from the peritoneum of rats by enzymatic digestion as previously described [33]. To identify PMCs, the cells were examined for specific markers and morphology as described elsewhere [33].…”

Section: Methodsmentioning

confidence: 99%

“…To identify PMCs, the cells were examined for specific markers and morphology as described elsewhere [33]. Cells between passages 3 and 6 were used for experiments.…”

Section: Methodsmentioning

confidence: 99%

Aliskiren Prevents the Toxic Effects of Peritoneal Dialysis Fluids during Chronic Dialysis in Rats

Pérez-Martínez

Pérez-Martínez²,

Carrión³

et al. 2012

PLoS ONE

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The benefits of long-term peritoneal dialysis (PD) in patients with end-stage renal failure are short-lived due to structural and functional changes in the peritoneal membrane. In this report, we provide evidence for the in vitro and in vivo participation of the renin-angiotensin-aldosterone system (RAAS) in the signaling pathway leading to peritoneal fibrosis during PD. Exposure to high-glucose PD fluids (PDFs) increases damage and fibrosis markers in both isolated rat peritoneal mesothelial cells and in the peritoneum of rats after chronic dialysis. In both cases, the addition of the RAAS inhibitor aliskiren markedly improved damage and fibrosis markers, and prevented functional modifications in the peritoneal transport, as measured by the peritoneal equilibrium test. These data suggest that inhibition of the RAAS may be a novel way to improve the efficacy of PD by preventing inflammation and fibrosis following peritoneal exposure to high-glucose PDFs.

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“…Nevertheless, statins are safe in high-risk PD patients and display anti-inflammatory effects reflected in reduced serum CRP levels together with the conventional lipid-lowering effect [ 239 ]. In rat and human peritoneal mesothelial cells cultured under high glucose conditions or high glucose-PDF exposition, statins (fluvastatin, atorvastatin, or simvastatin) are protective by modulating the serum- and glucocorticoid-inducible kinase 1 (SGK1) or phospho-p38 MAPK pathways, thus inhibiting the production of growth factors and preventing MMT [ 240 , 241 , 242 ]. In rat PDF exposure models, atorvastatin preserved ultrafiltration and decreased protein loss and PM thickness [ 243 ] and simvastatin restored MMT-induced changes such as those observed in E-cadherin, α-SMA, Snail, and fibronectin expression [ 241 ].…”

Section: Pharmacological Interference With the Th17 Immune Responsmentioning

confidence: 99%

IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis

et al. 2020

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Chronic kidney disease (CKD) is a health problem reaching epidemic proportions. There is no cure for CKD, and patients may progress to end-stage renal disease (ESRD). Peritoneal dialysis (PD) is a current replacement therapy option for ESRD patients until renal transplantation can be achieved. One important problem in long-term PD patients is peritoneal membrane failure. The mechanisms involved in peritoneal damage include activation of the inflammatory and immune responses, associated with submesothelial immune infiltrates, angiogenesis, loss of the mesothelial layer due to cell death and mesothelial to mesenchymal transition, and collagen accumulation in the submesothelial compact zone. These processes lead to fibrosis and loss of peritoneal membrane function. Peritoneal inflammation and membrane failure are strongly associated with additional problems in PD patients, mainly with a very high risk of cardiovascular disease. Among the inflammatory mediators involved in peritoneal damage, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases, including CKD. Although IL-17A is the hallmark cytokine of Th17 immune cells, many other cells can also produce or secrete IL-17A. In the peritoneum of PD patients, IL-17A-secreting cells comprise Th17 cells, γδ T cells, mast cells, and neutrophils. Experimental studies demonstrated that IL-17A blockade ameliorated peritoneal damage caused by exposure to PD fluids. This article provides a comprehensive review of recent advances on the role of IL-17A in peritoneal membrane injury during PD and other PD-associated complications.

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Atorvastatin Reduces High Glucose Toxicity in Rat Peritoneal Mesothelial Cells

Abstract: The present study shows that high glucose may promote oxidative stress and may activate apoptotic pathways in rat PMCs. These toxic effects could be reversed by atorvastatin.

Cited by 8 publications

References 49 publications

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

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

Aliskiren Prevents the Toxic Effects of Peritoneal Dialysis Fluids during Chronic Dialysis in Rats

IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis

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