PMID- 32991316 OWN - NLM STAT- MEDLINE DCOM- 20210714 LR - 20210714 IS - 1899-1505 (Electronic) IS - 0867-5910 (Linking) VI - 71 IP - 3 DP - 2020 Jun TI - N-acetylcysteine modulates effect of the iron isomaltoside on peritoneal mesothelial cells. LID - 10.26402/jpp.2020.3.07 [doi] AB - Intravenous (i.v.) iron supplementation is used in patients on chronic peritoneal dialysis (pd). Iron induced intraperitoneal inflammation observed in our previous studies with iron sucrose may deteriorate the function of the peritoneum as the dialysis membrane. We evaluated effect iron compound, iron-isomaltoside-100 (IIS) on the peritoneal mesothelial cells (MC). We studied the effect of iv treatment with IIS +/- N-acetylcysteine (NAC) on the dialysate parameters and function of MC. In 7 uremic pd patients IIS 200 mg was infused i.v. +/- NAC 600 mg. Afterward, a 4 hours exchange was performed with Dianeal 1.5%. As a control dialysate exchange preceding IIS treatment was used. Inflammatory parameters of the drained dialysates as well as the dialysates and IIS effects on MC were evaluated in ex vivo experiments. Intravenous infusion of IIS resulted in an increase of the dialysate Fe (+147%, P < 0.01). Concentrations of the dialysates inflammatory mediators were increased: interleukin-6 (IL-6) +39%, P < 0.02, monocyte chemoattractant protein-1(MCP1) +50%, P < 0.02, and hyaluronan (HA) +64%, P < 0.02. Simultaneous i.v. infusion of NAC prevented increase of the dialysate inflammatory mediators. Dialysates collected after IIS treatment induced oxidative stress in MC (+29%, P < 0.05) and stimulated IL-6 synthesis (+64%, P < 0.05) in MC; no such effect was seen in dialysates obtained after simultaneous IIS and NAC i.v. treatment. IIS used as the additive to culture medium stimulated synthesis in MC of IL6 (+76%, P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (28%, P < 0.001) whereas synthesis of tissue plasminogen activator (t-PA) was reduced (-16%, P < 0.001). These changes were prevented in the presence of NAC 1 mmol/L. Intravenous administration of IIS results in the mild stimulation of intraperitoneal inflammation. IIS changes MC phenotype to the inflammatory one with reduced fibrinolytic activity. These effects are prevented by NAC. FAU - Misian, M AU - Misian M AD - Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Baum, E AU - Baum E AD - Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Breborowicz, A AU - Breborowicz A AD - Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland. abreb@ump.edu.pl. LA - eng PT - Journal Article DEP - 20200926 PL - Poland TA - J Physiol Pharmacol JT - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JID - 9114501 RN - 0 (Cytokines) RN - 0 (Disaccharides) RN - 0 (Ferric Compounds) RN - 0 (Inflammation Mediators) RN - 3M6325NY1R (iron isomaltoside 1000) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/*administration & dosage/adverse effects MH - Adult MH - Cells, Cultured MH - Cytokines/metabolism MH - Disaccharides/*administration & dosage/adverse effects MH - Epithelial Cells/*drug effects/metabolism MH - Ferric Compounds/*administration & dosage/adverse effects MH - Fibrinolysis/drug effects MH - Humans MH - Inflammation Mediators/metabolism MH - Infusions, Intravenous MH - Male MH - Middle Aged MH - Oxidative Stress/drug effects MH - *Peritoneal Dialysis/adverse effects MH - Peritoneum/*drug effects/metabolism MH - Phenotype MH - Treatment Outcome MH - Uremia/blood/diagnosis/*therapy EDAT- 2020/09/30 06:00 MHDA- 2021/07/15 06:00 CRDT- 2020/09/29 17:13 PHST- 2020/05/09 00:00 [received] PHST- 2020/06/30 00:00 [accepted] PHST- 2020/09/29 17:13 [entrez] PHST- 2020/09/30 06:00 [pubmed] PHST- 2021/07/15 06:00 [medline] AID - 10.26402/jpp.2020.3.07 [doi] PST - ppublish SO - J Physiol Pharmacol. 2020 Jun;71(3). doi: 10.26402/jpp.2020.3.07. Epub 2020 Sep 26.