Beneficial effects of aminoguanidine on peritoneal microcirculation and tissue remodelling in a rat model of PD. |
| |
Authors: | Mohammad Zareie Geert-Jan Tangelder Piet M ter Wee Liesbeth H P Hekking Anton A van Lambalgen Eelco D Keuning Inge L Schadee-Eestermans Casper G Schalkwijk Robert H J Beelen Jacob van den Born |
| |
Affiliation: | Department of Molecular Cell Biology and Immunology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. m.zareie@vumc.nl. |
| |
Abstract: | BACKGROUND: The formation of glucose degradation products (GDPs) and accumulation of advanced glycation end products (AGEs) partly contribute to the bioincompatibility of peritoneal dialysis fluids (PDF). Aminoguanidine (AG) scavenges GDPs and prevents the formation of AGEs. METHODS: In a peritoneal dialysis (PD) rat model, we evaluated the effects of the addition of AG to the PDF on microcirculation and morphology of the peritoneum, by intravital microscopy and quantitative morphometric analysis. RESULTS: AG-bicarbonate effectively scavenged different GDPs from PDF. Daily exposure to PDF for 5 weeks resulted in a significant increase in leucocyte rolling in mesenteric venules, which could be reduced for approximately 50% by addition of AG-bicarbonate (P<0.02). Vascular leakage was found in rats treated with PDF/AG-bicarbonate, but not with PDF alone. Evaluation of visceral and parietal peritoneum showed the induction of angiogenesis and fibrosis after PDF instillation. PDF/AG-bicarbonate significantly reduced vessel density in omentum and parietal peritoneum (P<0.04), but not in mesentery. PDF-induced fibrosis was significantly reduced by AG (P<0.02). PDF instillation led to AGE accumulation in mesentery, which was inhibited by supplementation of AG. Since addition of AG-bicarbonate to PDF raised pH from 5.2 to 8.5, a similar experiment was performed with AG-hydrochloride that did not change the fluid acidity. We could reproduce most of the results obtained with AG-bicarbonate; however, AG-hydrochloride induced no microvascular leakage and had a minor effect on angiogenesis. CONCLUSION: The supplementation of either AG reduced a number of PDF-induced alterations in our model, emphasizing the involvement of GDPs and/or AGEs in the PDF-induced peritoneal injury. |
| |
Keywords: | aminoguanidine angiogenesis fibrosis peritoneal dialysis rats |
本文献已被 Oxford 等数据库收录! |
|