Department of Pharmacology and Toxicology, Mansoura University, Egypt. ghmsuddek @ yahoo.com
Chemotherapy. 2011;57(4):321-6. doi: 10.1159/000329529. Epub 2011 Sep 1.
Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors. Nevertheless, nephrotoxicity has restricted its clinical use. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Celecoxib, a selective cyclooxygenase-2 inhibitor used as anti-inflammatory, may therefore have a protective effect on cisplatin-induced renal injury.
In the present study, rats were injected intraperitoneally with a single dose of cisplatin (7 mg/kg) and/or celecoxib (30 mg/kg) for 5 days.
Nephrotoxicity manifested biochemically by elevations in serum creatinine, blood urea nitrogen, and proteinuria, and an increase in kidney weight as a percentage of total body weight. In addition, a marked decrease in serum albumin was observed. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde level and glutathione content, which were increased and depleted, respectively. Administration of celecoxib with cisplatin attenuated cisplatin-induced changes in kidney function parameters and oxidative stress markers. Histopathological examination of the kidney confirmed these results.
In conclusion, this study indicates that celecoxib may be a promising drug for clinical use as a nephroprotectant against cisplatin-induced nephrotoxicity.
顺铂是一种有效的化疗药物，成功地用于治疗多种肿瘤。然而，肾毒性限制了其临床应用。最近的研究强烈表明，炎症机制可能在顺铂肾毒性的发病机制中起重要作用。塞来昔布，一种用作抗炎药的选择性环氧化酶-2 抑制剂，因此可能对顺铂诱导的肾损伤具有保护作用。
在本研究中，大鼠腹腔注射单次剂量的顺铂（7mg/kg）和/或塞来昔布（30mg/kg），共 5 天。
顺铂肾毒性表现为血清肌酐、血尿素氮和蛋白尿升高，以及肾脏重量占体重的百分比增加。此外，血清白蛋白明显减少。通过测量丙二醛水平和谷胱甘肽含量来监测肾脏的脂质过氧化，分别升高和耗竭。顺铂联合塞来昔布可减轻顺铂诱导的肾功能参数和氧化应激标志物的变化。肾脏的组织病理学检查证实了这些结果。
综上所述，本研究表明，塞来昔布可能是一种有前途的药物，可作为临床应用的肾保护剂，用于预防顺铂引起的肾毒性。
