PMID- 16641917 OWN - NLM STAT- MEDLINE DCOM- 20061026 LR - 20061115 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 69 IP - 11 DP - 2006 Jun TI - Oxidative stress during peritoneal dialysis: implications in functional and structural changes in the membrane. PG - 2022-8 AB - Progressive peritoneal fibrosis, membrane hyperpermeability, and ultrafiltration failure have been observed in patients on long-term peritoneal dialysis (PD). The present study tested the hypothesis that reactive oxygen species (ROS) generated by conventional PD solution (PDS) mediate functional and structural alterations of peritoneal membrane in vivo. Sprague-Dawley rats were randomized to control, PDS, PDS with an antioxidant, and PDS with an angiotensin II (Ang II) receptor blocker. Commercial PDS containing 3.86% glucose (20-30 ml) with or without N-acetylcystein (NAC) 10 mM or losartan 5 mg/kg was administered intraperitoneally twice a day for 12 weeks. Control rats received sham injection. Rats treated with PDS had significantly lower drain volume and D(4)/D(0) glucose, but higher D(4)/P(4) creatinine and increased membrane thickness and endothelial NOS (eNOS) expression compared to control rats. Omental transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), collagen I, and heat-shock protein (hsp) 47 expression and lipid peroxide levels and dialysate VEGF and Ang II concentrations were significantly increased in rats treated with PDS compared to control. All of these changes were prevented by both NAC and losartan. In conclusion, the present study demonstrates that ROS generated by conventional PDS are, in large part, responsible for peritoneal fibrosis and membrane hyperpermeability. We suggest that antioxidants or Ang II receptor blockers may allow better preservation of the structural and functional integrity of the peritoneal membrane during long-term PD. FAU - Noh, H AU - Noh H AD - Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea. FAU - Kim, J S AU - Kim JS FAU - Han, K-H AU - Han KH FAU - Lee, G T AU - Lee GT FAU - Song, J S AU - Song JS FAU - Chung, S H AU - Chung SH FAU - Jeon, J S AU - Jeon JS FAU - Ha, H AU - Ha H FAU - Lee, H B AU - Lee HB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Reactive Oxygen Species) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/pharmacology MH - Animals MH - Male MH - *Oxidative Stress/drug effects MH - *Peritoneal Dialysis MH - Peritoneum/drug effects/*metabolism/*pathology MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism EDAT- 2006/04/28 09:00 MHDA- 2006/10/27 09:00 CRDT- 2006/04/28 09:00 PHST- 2006/04/28 09:00 [pubmed] PHST- 2006/10/27 09:00 [medline] PHST- 2006/04/28 09:00 [entrez] AID - S0085-2538(15)51424-5 [pii] AID - 10.1038/sj.ki.5001506 [doi] PST - ppublish SO - Kidney Int. 2006 Jun;69(11):2022-8. doi: 10.1038/sj.ki.5001506.