Sulfasalazine reduces inflammatory renal injury in unilateral ureteral obstruction.
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.
Demirbilek
Savas
S
Department of Pediatric Surgery, Inönü University School of Medicine, Malatya, Turkey. sdemirbilek@inonu.edu.tr
Emre
Memet Hanefi
MH
Aydin
Engin Nasuhi
EN
Edali
Mehmet Naci
MN
Aksoy
Rauf Tuğrul
RT
Akin
Melih
M
Gürünlüoğlu
Kubilay
K
Tas
Erkan
E
Ay
Selma
S
Yilmaz
Zümrüt
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009395:Nephritis, Interstitial / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012460:Sulfasalazine / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D012460:Sulfasalazine; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase