Sulfasalazine reduces inflammatory renal injury in unilateral ureteral obstruction

• Published in: Pediatric nephrology (Berlin, West) Vol. 22; no. 6; pp. 804 - 812
• Main Authors: Demirbilek, Savas, Emre, Memet Hanefi, Aydin, Engin Nasuhi, Edali, Mehmet Naci, Aksoy, Rauf Tuğrul, Akin, Melih, Gürünlüoğlu, Kubilay, Tas, Erkan, Ay, Selma, Yilmaz, Zümrüt
• Format: Journal Article
• Language: English
• Published: Germany Springer 01-06-2007; Springer Nature B.V
• Subjects: Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Catalase - metabolism; Cellulose; Complications and side effects; Cytokines; Enzymes; Female; Fibrosis - etiology; Fibrosis - pathology; Fibrosis - prevention & control; Free Radical Scavengers - therapeutic use; Inflammation; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidneys; Lipid peroxidation; Lipid Peroxidation - drug effects; Lipids; Medicine; Nephritis, Interstitial - etiology; Nephritis, Interstitial - pathology; Nephritis, Interstitial - prevention & control; Nitrates; Oxidative stress; Oxidative Stress - drug effects; Patient outcomes; Peroxidase - metabolism; Plasma; Rats; Rats, Sprague-Dawley; Risk factors; Sulfasalazine; Sulfasalazine - therapeutic use; Superoxide Dismutase - metabolism; Tumor necrosis factor-TNF; Ureteral Obstruction - complications; Ureteral Obstruction - drug therapy; Ureteral Obstruction - pathology; United States; Turkey
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-006-0416-8

The purpose of this study was to test whether sulfasalazine has a protective action against interstitial inflammation and the development of renal fibrosis in obstructive nephropathy. Female rats were subjected to a sham (n = 10) or unilateral ureteral obstruction (UUO, n = 30). UUO was induced in rats by ligating the left ureter. Three days after operation, rats subjected to UUO were randomized to receive tretment with either sulfasalazine (100 mg/kg) or vehicle every day for the last 7 days of the experiment. At 10 days following UUO, the obstructed kidney exhibited tubulointerstitial injury and leukocyte infiltration (mainly monocytes) that were associated with high levels of reactive oxygen species, cytokines, transforming growth factor (TGF)-beta1, myeloperoxidase (MPO), and lipid peroxidation. Ten days after UUO, the obstructed kidney was also associated with increased nuclear factor kappa beta (NF-kappabeta) expression in saline-treated rats. Compared with sham-operated rats, UUO rat kidneys showed lower concentrations of antioxidant enzymes in the obstructed kidney tissue. All of these changes were significantly attenuated by treatment with sulfasalazine in the obstructed kidney. Sulfasalazine protected against the renal interstitial inflammation and tissue damage elicited by ureteral occlusion. Inhibition of the NF-kappabeta-dependent pathway and inflammatory response and oxidative stress inhibition is likely to be involved in the beneficial effects of sulfasalazine.