TNF alpha, DNA fragmentation, biochemical and histopathological changes of cisplatin induced nephrotoxicity. possible protective role of salicylate

ABSTRACT

Cisplatin is an antineoplastic drug with well known nephrotoxicity, meanwhile salicylate was recently shown to provide protection against oxidants injury of the kidneys in rats. To investigate the possibility to decrease the nephrotoxic effect of cisplatin by salicylate. A total of 120 rats were divided equally into four groups the first group was given 20 mg/kg cisplatin, the second was given 20mg/kg cisplatin and salicylate 100mg/kg, the third was given salicylate 100mg/kg and used as positive control and the fourth was given saline and used as negative control. Renal biochemical and histopathological changes, DNA fragmentation and tumor necrosis factor-a [TNF-alpha] were investigated. Salicylate significantly reduced both the functional and histological evidence of cisplatin renal injury. Cisplatin increased significantly the renal expression of TNF-alpha while concomitant administration of cisplatin with salicylate signifIcantly reduced serum TNF-alpha protein levels. Salicylate reduces cisplatin-induced nephrotoxicity as a result of inhibiting TNF-alpha production. Thus, further experimental and clinical studies on preparations of this combination are warranted