Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells

Witowski, Janusz; Wiśniewska, Justyna; Korybalska, Katarzyna; Bender, Thorsten O.; Bręborowicz, Andrzej; Gahl, Gerhard M.; Frei, Ulrich; Passlick–Deetjen, Jutta; Jörres, Achim

doi:10.1681/asn.v12112434

Cited by 164 publications

(12 citation statements)

References 29 publications

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“…The prolonged exposure to nonphysiological glucose-based PDSs can cause PMC injury during PD . To simulate the in vivo PD environment, we used HPMCs subjected to PDS containing 10% FBS.…”

Section: Resultsmentioning

confidence: 99%

“…The prolonged exposure to nonphysiological glucose-based PDSs can cause PMC injury during PD. 50 To simulate the in vivo PD environment, we used HPMCs subjected to PDS containing 10% FBS. PDS caused loss of cellular viability in a concentration-dependent fashion, which imitates 1.5, 2.5, and 4.25% glucose in PDS used in PD (Figure 5A).…”

Section: Ee and In Vitro Drugmentioning

confidence: 99%

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CXCR4-Receptor-Targeted Liposomes for the Treatment of Peritoneal Fibrosis

Khan

Zhou

et al. 2019

Mol. Pharmaceutics

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Peritoneal fibrosis (PF) is a common complication of long-term peritoneal dialysis (PD). It is considered as the main reason for dialysis inadequacy and PD withdrawal. Transforming growth factor beta (TGF-β) regulates the expression of stromal cell-derived factor 1 (SDF-1α) and its receptor C–X–C chemokine receptor type 4 (CXCR4) on human peritoneal mesothelial cells (HPMCs), resulting in an increased migratory potential of HPMCs and extracellular matrix (ECM) deposition in the scar tissue and eventually fibrosis. Because SDF-1α/CXCR4 activation has a vital role in the pathogenesis of PF, codelivery of a CXCR4-receptor targeting agent with an antifibrotic agent in a single nanocarrier can be a promising strategy for treating PF. Here, for the first time, AMD3100 (AMD), a CXCR4-receptor antagonist, was coformulated with sulfotanshinone IIA sodium (STS IIA) into a liposome (STS-AMD-Lips) to develop a CXCR4 receptor targeting form of combination therapy for PF. CXCR4 targeting increased the ability of liposomes to target fibrotic peritoneal mesothelial cells overexpressing CXCR4 and facilitated the ability of STS IIA treatment at the fibrotic site. The liposome had an average diameter of 103 nm with encapsulated efficiencies of above 50%. The in vivo studies confirmed the reversal of PD solution-induced epithelial-to-mesenchymal transition by STS-AMD-Lips in HPMCs. The in vivo studies also revealed the precise biodistribution of the liposomes to peritoneum. Significant reduction of the morphological lesions and decreased level of ECM proteins were observed in rats treated with STS-AMD-Lips, proving that the liposomal nanocarrier has excellent ability to reverse PF. It has been concluded that the STS-AMD-Lips exhibit specific peritoneal targeting ability and could be used to improve STS-AMD combination delivery for the treatment of PF.

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“…The prolonged exposure to nonphysiological glucose-based PDSs can cause PMC injury during PD . To simulate the in vivo PD environment, we used HPMCs subjected to PDS containing 10% FBS.…”

Section: Resultsmentioning

confidence: 99%

Section: Ee and In Vitro Drugmentioning

confidence: 99%

CXCR4-Receptor-Targeted Liposomes for the Treatment of Peritoneal Fibrosis

Khan

Zhou

et al. 2019

Mol. Pharmaceutics

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“… 21 , 22 GDPs in glucose‐containing PD fluids are formed during heat sterilization and storage and are associated with functional and morphological changes of the peritoneal membrane in vitro and in vivo. 23 , 24 , 25 , 26 , 27 , 28 , 29 Theoretically, glucose oxidation is likely to occur because glucose is abundantly present in the dialysate, in particular in peritoneal dialysate, and glucose may be oxidized at a relatively low redox potential. In accordance with this, several studies observed substantial glucose degradation during electrochemical dialysate treatment 30 , 31 , 32 and suggest that glucose was oxidized to gluconic acid, a nontoxic monocarboxylic acid.…”

Section: Discussionmentioning

confidence: 99%

“…GO and MGO concentrations in EO‐treated peritoneal effluent were ~220‐660‐fold and ~27‐46‐fold higher, respectively, than concentrations in commercial PD fluids containing glucose 1.5%‐4.25% 21,22 . GDPs in glucose‐containing PD fluids are formed during heat sterilization and storage and are associated with functional and morphological changes of the peritoneal membrane in vitro and in vivo 23‐29 . Theoretically, glucose oxidation is likely to occur because glucose is abundantly present in the dialysate, in particular in peritoneal dialysate, and glucose may be oxidized at a relatively low redox potential.…”

Section: Discussionmentioning

confidence: 99%

Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products

et al. 2021

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A major challenge for the development of a wearable artificial kidney (WAK) is the removal of urea from the spent dialysate, as urea is the waste solute with the highest daily molar production and is difficult to adsorb. Here we present results on glucose degradation products (GDPs) formed during electrooxidation (EO), a technique that applies a current to the dialysate to convert urea into nitrogen, carbon dioxide, and hydrogen gas. Uremic plasma and peritoneal effluent were dialyzed for 8 hours with a WAK with and without EO‐based dialysate regeneration. Samples were taken regularly during treatment. GDPs (glyoxal, methylglyoxal, and 3‐deoxyglucosone) were measured in EO‐ and non‐EO‐treated fluids. Glyoxal and methylglyoxal concentrations increased 26‐ and 11‐fold, respectively, in uremic plasma (at [glucose] 7 mmol/L) and 209‐ and 353‐fold, respectively, in peritoneal effluent (at [glucose] 100 mmol/L) during treatment with EO, whereas no change was observed in GDP concentrations during dialysate regeneration without EO. EO for dialysate regeneration in a WAK is currently not safe due to the generation of GDPs which are not biocompatible.

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“…Moreover, through production of IFN-gamma (IFN-γ) and transforming growth factor-β1 (TGF-β1), these cells may directly orchestrate the fibrotic process. Interleukin-l beta (IL-1β), IL-6, and TNF-α are proinflammatory hormones which trigger a persistent inflammatory response in the peritoneum, ultimately leading to structural changes in the peritoneum [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Does Far-Infrared Therapy Improve Peritoneal Function and Reduce Recurrent Peritonitis in Peritoneal Dialysis Patients?

Chang

Chang²,

Lee

et al. 2022

JCM

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The use of peritoneal dialysis in end-stage renal disease is increasing in clinical practice. The main purpose of this study was to evaluate the effect of far-infrared radiation therapy on inflammation and the cellular immunity of patients undergoing peritoneal dialysis. We recruited 56 patients undergoing peritoneal dialysis, and we included 32 patients for the experimental group and 24 patients from the control group in the final analysis. The experimental evaluation in our study was as follows: (1) We used abdominal computed tomography to explore the changes in abdominal blood vessels. (2) We compared the effects of peritoneal dialysis using blood glucose, HbAlC, albumin, urea nitrogen, creatinine, white blood cells, hs-CRP; peritoneal Kt/V of peritoneal function, and eGFR. (3) We compared the cytokines’ concentrations in the two groups while controlling for the other cytokines. Results and Discussion: (1) There was no significant difference in the abdominal blood vessels of the experimental group relative to the control group according to abdominal CT over the 6 months. (2) Our study demonstrates statistically significant effects of FIR therapy on the following parameters: creatinine (p = 0.039 *) and hs-CRP (p < 0.001 **) levels decreased significantly, and eGFR (p = 0.043 *), glucose (p < 0.001 **), and albumin (p = 0.048 *) levels increased significantly. Our study found that in the experimental group, creatinine and hs-CRP levels decreased significantly due to FIR therapy for 6 months. However, our study also found that the glucose level was significantly different after FIR therapy for 6 months. Peritoneal dialysis combined with FIR can reduce the side effects of the glucose in the dialysis buffer, which interferes with peritoneal inflammation and peritoneal mesothelial cell fibrosis. (3) In addition, we also found that no statistically significant difference in any inflammatory cytokine after FIR therapy. IFN-γ (p = 0.124), IL-12p70 (p = 0.093), IL-18 (p = 0.213), and TNF-α (p = 0.254) did not exhibit significant improvements after peritoneal dialysis with FIR treatment over 6 months. Conclusions: We found that the effectiveness of peritoneal dialysis was improved significantly with FIR therapy, and significant improvements in the peritoneal permeability and inflammatory response were observed.

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Prolonged Exposure to Glucose Degradation Products Impairs Viability and Function of Human Peritoneal Mesothelial Cells

Cited by 164 publications

References 29 publications

CXCR4-Receptor-Targeted Liposomes for the Treatment of Peritoneal Fibrosis

CXCR4-Receptor-Targeted Liposomes for the Treatment of Peritoneal Fibrosis

Safety of electrooxidation for urea removal in a wearable artificial kidney is compromised by formation of glucose degradation products

Does Far-Infrared Therapy Improve Peritoneal Function and Reduce Recurrent Peritonitis in Peritoneal Dialysis Patients?

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