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Icodextrin-induced lipid peroxidation disrupts the mesothelial cell cycle engine.
Lazaro Gotloib1, Valery Wajsbrot, Avshalom Shostak
1Department of Nephrology and Hypertension and the Research Center for Experimental Nephrology, "Ha'Emek" Medical Center, Afula, Israel. gotloib@netvision.net.il
Free Radical Biology & Medicine
|February 5, 2003
Summary
Peritoneal dialysis fluids containing glucose or icodextrin cause oxidative stress and cell damage. Long-term use leads to premature cell aging and DNA damage in the peritoneal membrane.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Nephrology
Background:
- Peritoneal dialysis (PD) fluids often exhibit poor biocompatibility with the peritoneal membrane.
- Osmotic agents in PD solutions are a primary cause of this reduced biocompatibility.
Purpose of the Study:
- To investigate the in vivo effects of glucose-enriched and icodextrin-based PD fluids on the rat peritoneal mesothelium.
- To assess the cellular and molecular mechanisms underlying PD fluid-induced peritoneal membrane injury.
Main Methods:
- In vivo exposure of rat mesothelium to glucose-enriched and 7.5% icodextrin PD solutions for short (2 h) and long (30 d) durations.
- Evaluation of cell cycle, senescence, oxidative stress markers, lipid peroxidation, and DNA damage.
Main Results:
- Short-term glucose exposure accelerated cell cycle; long-term exposure induced senescent, depopulated monolayers.
- Continuous exposure to high glucose led to oxidative stress and Maillard reaction products.
- 30-day exposure to 7.5% icodextrin caused senescent cells with atypical nuclear changes and mitosis, indicating DNA damage.
- Icodextrin induced immediate lipid peroxidation and subsequent genomic damage, triggering cellular suicide mechanisms.
Conclusions:
- Current osmotic agents in PD fluids cause significant oxidative injury to the peritoneal mesothelium in vivo.
- High glucose concentrations promote premature senescence.
- 7.5% icodextrin induces lipid peroxidation and genomic damage, initiating protective cellular responses like apoptosis.