Effect of sulfasalazine on renal ischemia/reperfusion injury in rats.
Renal ischemia/reperfusion (I/R) occurs during shock and transplant procedures, greatly affecting outcome. A definitive treatment has not been found. One of the pathophysiological bases of renal I/R injury is the activation of the transcription factor nuclear factor-kappaB (NF-KappaB). We studied the effects of sulfasalazine (SFZ), a NF-kappaB inhibitor, over renal injury in a bilateral renal I/R model in rats. Ten male Wistar rats were subjected to bilateral renal I/R for 45 min followed by 24 h of reperfusion. Half of these received 100 mg/kg SFZ orally before the induction of I/R, while the others received only saline. Five rats served as sham-operated controls. At the end of the reperfusion period, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), P-selectin, tumor necrosis factor-alpha (TNF-alpha), intracellular adhesion molecule-1 (ICAM-1), and endothelin-1 (ET-1) concentrations were determined in serum, and renal samples were taken for histological evaluation. After renal I/R, AST, LDH, BUN, TNF-alpha, ICAM-1, and ET-1 serum levels were significantly increased, and tubules were severely damaged on histological analysis, compared to sham controls. SFZ treatment reduced the AST, LDH, BUN, TNF-alpha, and ET-1 elevations, as well as the tubular damage, induced by renal I/R. Serum ICAM-1 and P-selectin were unchanged. These results show that SFZ has a protective effect over renal IR injury. The modulation of adhesion molecules probably does not play a part in these effects, but TNF-alpha and ET-1 modulation could be partly responsible for the effects we observed.
Cámara-Lemarroy
Carlos Rodrigo
CR
Departamento de Fisiología, Universidad Autónoma de Nuevo León, Facultad de Medicina, Monterrey, Nuevo León 64460, México. crcamara83@hotmail.com
Guzmán-de la Garza
Francisco Javier
FJ
Alarcón-Galván
Gabriela
G
Cordero-Pérez
Paula
P
Fernández-Garza
Nancy Esthela
NE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007674:Kidney Diseases / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control / Q000628:therapy*; D012460:Sulfasalazine / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D012460:Sulfasalazine