PMID- 32203941
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20200617
IS  - 1899-1505 (Electronic)
IS  - 0867-5910 (Linking)
VI  - 70
IP  - 6
DP  - 2019 Dec
TI  - Sulodexide modulates the dialysate effect on the peritoneal mesothelium.
LID - 10.26402/jpp.2019.6.15 [doi]
AB  - Peritoneal membrane damage during chronic peritoneal dialysis is the main cause 
      of that treatment failure. Preservation of the mesothelial cells (MC) is 
      important for the survival of the peritoneum. Evaluation of dialysates effect on 
      the function of MC and potential modification of that effect by sulodexide 
      (heparin 80% and dermatan sulfate 20%). Dialysate effluents, after the overnight 
      exchange with dianeal 1.5% dextrose, were collected from 7 continuous ambulatory 
      peritoneal dialysis (CAPD) patients, and their effect +/- sulodexide 0.5 LRU/mL on 
      genes expression, secretory activity and protein synthesis in MC was studied. 
      Exposure of MC to the studied dialysates caused intracellular oxidative stress 
      and significantly increased expression of the genes regulating the synthesis of 
      interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), transforming 
      growth factor-beta (TGF-beta), vascular cell adhesion molecule 1 (VCAM-1) and 
      vascular endothelial growth factor (VEGF). Secretion of the studied molecules 
      from MC treated with dialysates was increased: by 96% for IL-6 (P < 0.01), 34% 
      for MCP-1(P < 0.01), 24% for TGF-beta (P < 0.01), 27% for VCAM-1 (P < 0.01), and by 
      15% for VEGF (P < 0.01). Sulodexide reduced the stimulatory effect of the 
      dialysates on the intracellular generation of free radicals, genes expression and 
      secretory activity of MC. These cells exposed to the dialysates showed increased 
      synthesis of total protein (by 216%, P < 0.005) and collagen (by 264%, P < 
      0.005), as compared to standard culture medium. Supplementation of the dialysates 
      with sulodexide resulted in weaker stimulation of collagen synthesis (-21% versus 
      dialysate). We concluded that peritoneal dialysate changes the genes expression 
      and phenotype of MC to a proinflammatory, profibrotic and proangiogenic one. 
      Sulodexide reduces these negative effects of the dialysate.
FAU - Misian, M
AU  - Misian M
AD  - Department of Pathophysiology, University Medical School, Poznan, Poland.
FAU - Baum, E
AU  - Baum E
AD  - Department of Pathophysiology, University Medical School, Poznan, Poland.
FAU - Breborowicz, A
AU  - Breborowicz A
AD  - Department of Pathophysiology, University Medical School, Poznan, Poland. 
      abreb@ump.edu.pl.
LA  - eng
PT  - Journal Article
DEP - 20200320
PL  - Poland
TA  - J Physiol Pharmacol
JT  - Journal of physiology and pharmacology : an official journal of the Polish 
      Physiological Society
JID - 9114501
RN  - 0 (Anticoagulants)
RN  - 0 (Dialysis Solutions)
RN  - 0 (Glycosaminoglycans)
RN  - 75HGV0062C (glucuronyl glucosamine glycan sulfate)
SB  - IM
MH  - Anticoagulants/pharmacology
MH  - Cells, Cultured
MH  - Dialysis Solutions/*adverse effects
MH  - Epithelium/metabolism
MH  - Gene Expression Regulation
MH  - Glycosaminoglycans/*pharmacology
MH  - Humans
MH  - Oxidative Stress
MH  - Peritoneal Dialysis, Continuous Ambulatory/*methods
MH  - Peritoneum/*metabolism
EDAT- 2020/03/24 06:00
MHDA- 2020/06/18 06:00
CRDT- 2020/03/24 06:00
PHST- 2019/10/31 00:00 [received]
PHST- 2019/12/30 00:00 [accepted]
PHST- 2020/03/24 06:00 [entrez]
PHST- 2020/03/24 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
AID - 10.26402/jpp.2019.6.15 [doi]
PST - ppublish
SO  - J Physiol Pharmacol. 2019 Dec;70(6). doi: 10.26402/jpp.2019.6.15. Epub 2020 Mar 
      20.