Fibrosis is the end point of most renal disease, eventually leading to organ insufficiency. The initial injury phase of interstitial fibrosis is characterized by activation of cells. Mononuclear cells migrate into the interstitiun and mature into macrophages, release cytokines that contribute to the inflammation environment and the development of the fibrogenic process. Although not well elucidated this process involved expression of leukocyte adhesion molecules such selectins, vascular cell adhesion molecules (ICAM and VCAM), cytokines and others growth factors. In the present work we investigate the molecular and cellular events involved in the evolution of renal disease and the protetive effect of fucosylated chondroitin sulfate. This polysaccharide administered by into peritoneal route during 14 days prevents fibrosis (~50%) on a model of unilateral ureteral obstruction (UUO) in mice, as indicated by histomorphometry and biochemical methods. The hydroxiproline (mg HO-PRO/mg tissue dry weight), control (0,5 ± 0,3); UUO (8,7 ± 1,031) compared UUO+fucs-CS (5,46 ± 1,43) p< 0,01. The study with Sirius Red staining (mm²) revealed higher density in group UUO (5499,592 ± 2918,86) compared to UUO+fucs-CS (1286,592 ± 674,88) p< 0,001, control(319,42 ± 384,13); sham( 349,03 ± 340,07) . At the dose UUO, fucosylated chondroitin sulfate has no anticoagulant effects. Fucosylated chondroitin sulfate changes the cytokine release, leukocyte migration and expression of inflammatory mediators on kidney, as indicated by immunohistochemical analysis. We hope to clarify the role of fucosylated chondroitin sulfate on the evolution of renal disease and to correlate the in vitro effect of the sulfated polysaccharide on selectin binding with their in vivo renal protetive effect.

Financial support: CAPES, CNPq, FAPERJ