BACKGROUND: Peritoneal dialysis with @entity413 - and @entity880 -containing dialysis solutions stimulates peritoneal @entity7499 and @entity82 . These serious side effects can also be induced by chronic peritoneal exposure to dialysis solutions in nonuremic @entity35 . The high @entity413 concentrations of the dialysis solutions may saturate physiological @entity413 metabolism pathways and stimulate the @entity8371 pathway that has been described to damage nerves and vessels in @entity6 . To investigate the role of the @entity8371 pathway in the development of @entity82 and @entity7499 during chronic peritoneal exposure, the rate-limiting @entity3650 reductase activity in the @entity8371 pathway was inhibited in a chronic peritoneal exposure model in the @entity35 , in which different administration routes were compared. EXPERIMENTAL PROCEDURES: Three groups of @entity35 received daily intraperitoneal infusion with @entity880 / @entity413 (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, @entity68146 , administered either orally (group 2) or intraperitoneally (group 3). After sacrifice, omental tissue was examined by histology for the presence of @entity82 (Picro Sirius Red) and the number of blood vessels ( @entity18518 ). 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 @entity18518 -positive vessels perfield in both groups treated with @entity68146 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 @entity68146 , a newly developed inhibitor of @entity3650 reductase activity, resulted in less @entity82 and fewer peritoneal vessels than exposure to dialysis fluids only, in a long-term exposure model in the @entity35 . Inhibition of the @entity8371 pathway may thus offer an important contribution to allow long-term continuation of peritoneal dialysis.

Effects of inhibition of the XXXX pathway during chronic peritoneal exposure to a dialysis solution.

@entity18518 :: ('29583(Tax:10116)', 'Gene') :: ['CD31'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity7499 :: ('MESH:D016510', 'Disease') :: ['angiogenesis'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes mellitus'] @entity68146 :: ('MESH:C067172', 'Chemical') :: ['zopolrestat'] @entity880 :: ('MESH:D019344', 'Chemical') :: ['lactate'] @entity3650 :: ('CHEBI:15693', 'Chemical') :: ['aldose'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose'] @entity8371 :: ('CHEBI:26191', 'Chemical') :: ['polyol']
@entity8371 :: (CHEBI:26191,Chemical) :: ['polyol']
