Icodextrin-induced lipid peroxidation disrupts the mesothelial cell cycle engine.
Fluids commonly used for peritoneal dialysis hold poor biocompatibility vis a vis the peritoneal membrane, basically due to the presence of osmotic agents. When rat mesothelium was exposed to glucose-enriched dialysis solutions for 2 h in vivo, an early and short-lived acceleration of cell life cycle was observed, which, after 30 d of exposure, resulted in a depopulated monolayer of senescent cells. These changes appear to result from persistent oxidative stress due to continuous exposure to high concentration of glucose and to substances generated by the Maillard reaction. Long-term exposure (30 d) of the peritoneal mesothelium to 7.5% icodextrin resulted in a depopulated monolayer consisting mostly of senescent cells, which, additionally, showed atypical nuclear changes and atypical mitosis suggesting DNA damage. These changes coincided with substantial lipid peroxidation, starting immediately after the introduction of the icodextrin solution into the rat's abdominal cavity. So far, the currently used osmotic agents in peritoneal dialysis fluids induce substantial oxidative injury to the exposed monolayer in vivo. Use of high concentrations of glucose results in premature senescence of the exposed cell population. The 7.5% icodextrin dialysis fluid induces through lipid peroxidation substantial genomic damage, which, in turn, sets the biological mechanisms leading to protective cellular suicide in motion.
Gotloib
Lazaro
L
Department of Nephrology and Hypertension and the Research Center for Experimental Nephrology, "Ha'Emek" Medical Center, Afula, Israel. gotloib@netvision.net.il
Wajsbrot
Valery
V
Shostak
Avshalom
A
D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects*; D016922:Cellular Senescence; D015314:Dialysis Solutions / Q000009:adverse effects* / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects*; D005936:Glucans / Q000009:adverse effects* / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D000077607:Icodextrin; D015227:Lipid Peroxidation / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010530:Peritoneal Dialysis
D015314:Dialysis Solutions; D005936:Glucans; D000077607:Icodextrin; D005947:Glucose