Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Experimental Chemotherapy Chemotherapy 2011;57:321–326 DOI: 10.1159/000329529 Celecoxib, a Selective Cyclooxygenase-2 Inhibitor, Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity Ghada M. Suddek   a Asmaa E. El-kenawi   a Azza Abdel-Aziz   b Hassan A. El-Kashef   a a  Department of Pharmacology and Toxicology, Faculty of Pharmacy, and b  Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt kidney confirmed these results. Conclusion: In conclusion, this study indicates that celecoxib may be a promising drug for clinical use as a nephroprotectant against cisplatin- induced nephrotoxicity. Copyright © 2011 S. Karger AG, Basel Introduction Cisplatin is a major anti-neoplastic drug for the treat- ment of solid tumors, but dose-dependent renal toxicity limits the use of optimal doses of this drug. Cisplatin has intracellular effects on proximal straight and distal con- voluted tubules. Little is known about the molecular mechanism of cisplatin-induced nephrotoxicity, and che- moprotection against cisplatin-induced nephrotoxicity has not been achieved via a mechanistic approach. DNA damage, oxidative stress, apoptosis, and inflammation have been implicated in the pathogenesis of cisplatin-in- duced renal injury [1]. Recent studies have shown in- creased tissue content of inflammatory mediators, sug- gesting that inflammation plays an important role in cis- platin-induced renal injury. Faubel et al. [2] demonstrated that cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1 , IL- 18, and IL-6 and neutrophil infiltration in the kidney. Key Words Celecoxib  Cisplatin  Inflammation  Renal tubular injury Abstract Background: Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors. Nevertheless, nephrotoxicity has restricted its clini- cal use. Recent studies have strongly suggested that inflam- matory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Celecoxib, a selec- tive cyclooxygenase-2 inhibitor used as anti-inflammatory, may therefore have a protective effect on cisplatin-induced renal injury. Methods: In the present study, rats were inject- ed intraperitoneally with a single dose of cisplatin (7 mg/kg) and/or celecoxib (30 mg/kg) for 5 days. Results: Nephrotox- icity manifested biochemically by elevations in serum cre- atinine, blood urea nitrogen, and proteinuria, and an in- crease in kidney weight as a percentage of total body weight. In addition, a marked decrease in serum albumin was ob- served. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde level and glutathione con- tent, which were increased and depleted, respectively. Ad- ministration of celecoxib with cisplatin attenuated cisplatin- induced changes in kidney function parameters and oxida- tive stress markers. Histopathological examination of the Received: September 21, 2010 Accepted after revision: April 5, 2011 Published online: September 1, 2011 Ghada M. Suddek Department of Pharmacology and Toxicology Faculty of Pharmacy, Mansoura University Mansoura 35516 (Egypt) Tel. +20 10 126 6745, E-Mail ghmsuddek  @  yahoo.com © 2011 S. Karger AG, Basel 0009–3157/11/0574–0321$38.00/0 Accessible online at: www.karger.com/che