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

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

Cardio-renal effects of celecoxib versus ibuprofen in patients with arthritis

Arthritis is a common condition that co-exists in the elderly population. This condition leads to frequent administration of co-morbid Non Steroidal Anti-inflammatory drugs [NSAIDs]. To study cardio-renal toxicity of celecoxib versus ibuprofen in arthritic patients. Seven hundred ninety two arthritic patients were enrolled in the study for 6 months. Three hundred ninty six patients administered celecoxib, 400 mg twice a day; 396 patients administered ibuprofen 300 mg three times a day Effects measured included: investigator reported hypertension, edema, or congestive heart failure, and increases in serum creatinine or reduction in serum creatinine clearance, and changes in serum electrolytes. Celecoxib was associated with significant [P<0.05] lower incidence of hypertension and edema in comparison with ibuprofen. Systolic hypertension occurred significantly less [P<0.05] with celecoxib compared with ibuprofen. Serum creatinine was significantly increased [P<0.05] in patients treated with ibuprofen in comparison with celecoxib. Creatinine clearance was significantly lower [P<0.05] in cases treated with ibuprofen in comparison to celecoxib. Non significant changes in serum body electrolytes. The most important finding of this study was the lowering incidence of cardiorenal complications of celecoxib in comparison with ibuprofen