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Basic Clin Pharmacol Toxicol ; 123(4): 494-503, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29753311

ABSTRACT

Metabolic syndrome (MetS) is commonly observed among peritoneal dialysis (PD) patients, and hyperbranched polyglycerol (HPG) is a promising glucose-sparing osmotic agent for PD. However, the biocompatibility of a HPG-based PD solution (HPG) in subjects with MetS has not been investigated. This study compared the local and systemic effects of a HPG solution with conventional physioneal (PYS) and icodextrin (ICO) PD solutions in rats with MetS. Obese type 2 diabetic ZSF1 rats received a daily intraperitoneal injection of PD solutions (10 mL) for 3 months. The peritoneal membrane (PM) function was determined by ultrafiltration (UF), and the systemic responses were determined by profiling blood metabolic substances, cytokines and oxidative status. Tissue damage was assessed by histology. At the end of the 3-month treatment with PD solutions, PM damage and UF loss in both the PYS and ICO groups were greater than those in the HPG group. Blood analyses showed that compared to the baseline control, the rats in the HPG group exhibited a significant decrease only in serum albumin and IL-6 and a minor glomerular injury, whereas in both the PYS and ICO groups, there were more significant decreases in serum albumin, antioxidant activity, IL-6, KC/GRO (CXCL1) and TNF-α (in ICO only) as well as a more substantial glomerular injury compared to the HPG group. Furthermore, PYS increased serum creatinine, serum glucose and urine production. In conclusion, compared to PYS or ICO solutions, the HPG solution had less adverse effects locally on the PM and systemically on distant organs (e.g. kidneys) and the plasma oxidative status in rats with MetS.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Dialysis Solutions/toxicity , Glycerol/toxicity , Icodextrin/toxicity , Kidney/drug effects , Obesity/metabolism , Peritoneal Dialysis/adverse effects , Peritoneum/drug effects , Polymers/toxicity , Animals , Biomarkers/blood , Cytokines/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Dialysis Solutions/administration & dosage , Disease Models, Animal , Glycerol/administration & dosage , Icodextrin/administration & dosage , Inflammation Mediators/blood , Injections, Intraperitoneal , Kidney/metabolism , Kidney/physiopathology , Male , Obesity/blood , Obesity/genetics , Obesity/physiopathology , Organic Chemicals/administration & dosage , Organic Chemicals/toxicity , Oxidative Stress/drug effects , Peritoneal Dialysis/methods , Peritoneum/metabolism , Peritoneum/physiopathology , Permeability , Polymers/administration & dosage , Rats, Zucker , Time Factors
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