Effects of Inhibition of the Polyol Pathway during Chronic Peritoneal Exposure to a Dialysis Solution

腹膜透析 医学 多元醇 透析 多元醇途径 重症监护医学 药理学 内科学 泌尿科 内分泌学 化学 有机化学 醛糖还原酶 聚氨酯 糖尿病
作者
Roos van Westrhenen,Jan Aten,Medhanit Aberra,Cindy A M Dragt,Gregory Deira,Raymond T. Krediet
出处
期刊:Peritoneal Dialysis International [SAGE Publishing]
卷期号:25 (3_suppl): 18-21 被引量:11
标识
DOI:10.1177/089686080502503s05
摘要

♦ Background Peritoneal dialysis with glucose- and lactate-containing dialysis solutions stimulates peritoneal angiogenesis and fibrosis. These serious side effects can also be induced by chronic peritoneal exposure to dialysis solutions in nonuremic rats. The high glucose concentrations of the dialysis solutions may saturate physiological glucose metabolism pathways and stimulate the polyol pathway that has been described to damage nerves and vessels in diabetes mellitus. To investigate the role of the polyol pathway in the development of fibrosis and angiogenesis during chronic peritoneal exposure, the rate-limiting aldose reductase activity in the polyol pathway was inhibited in a chronic peritoneal exposure model in the rat, in which different administration routes were compared. ♦ Experimental Procedures Three groups of rats received daily intraperitoneal infusion with lactate/glucose (3.86%)- containing dialysate via a peritoneal catheter with a subcutaneous puncture device, for 14 weeks: group 1 received only the dialysis solution, groups 2 and 3 received, in addition, zopolrestat, administered either orally (group 2) or intraperitoneally (group 3). After sacrifice, omental tissue was examined by histology for the presence of fibrosis (Picro Sirius Red) and the number of blood vessels (CD31). ♦ Results Histology revealed significantly less Picro Sirius Red-positive tissue in perivascular areas of both experimental groups and submesothelial areas of the oral group in comparison to the control group. There were significantly fewer CD31-positive vessels per field in both groups treated with zopolrestat compared to the infusion-only group: group 2, 9 (7 – 12); group 3, 17 (13 – 38), compared to group 1, 37 (32 – 39), p < 0.05. ♦ Conclusion The combination of peritoneal exposure to dialysis fluids and administration of zopolrestat, a newly developed inhibitor of aldose reductase activity, resulted in less fibrosis and fewer peritoneal vessels than exposure to dialysis fluids only, in a long-term exposure model in the rat. Inhibition of the polyol pathway may thus offer an important contribution to allow long-term continuation of peritoneal dialysis.
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