Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Oman.
Food Chem Toxicol. 2010 Jan;48(1):139-44. doi: 10.1016/j.fct.2009.09.030. Epub 2009 Sep 26.
We investigated the effect of administration of nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on cisplatin (CP)-induced nephrotoxicity in rats. WKY rats and SHRs were divided into four groups, each. The first and second groups received saline and oral nimesulide (20mg/kg/day for 6 days), respectively, whereas the third and fourth groups received a single intraperitoneal (i.p.) injection of CP (5mg/kg) and CP (5mg/kg) and nimesulide (20mg/kg/day for 5 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow (RBF) were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE). Nephrotoxicity was evaluated histopathologically and biochemically. CP caused a reduction in baseline RBF in both WKY and SHRs. It increased the concentrations of urea and creatinine and kidney relative weight, and decreased body weight in both WKY and SHRs. Histopathologically, CP caused remarkable renal damage in both WKY rats and SHRs. Treatment with nimesulide alone did not produce any significant change in any of the above measurements. However, nimesulide aggravated CP-induced renal tissue damage in SHRs, but not in WKY rats. The results show that administration nimesulide augmented the histopathological indices of nephrotoxicity in SHRs, but not in WKY rats.
我们研究了给予昔布类药物尼美舒利（一种选择性环氧化酶-2（COX-2）抑制剂）对大鼠顺铂（CP）诱导的肾毒性的影响。WKY 大鼠和 SHR 大鼠被分为四组，每组又分为两组。第一和第二组分别接受生理盐水和尼美舒利（20mg/kg/天，共 6 天）口服治疗，而第三和第四组则分别接受单次腹腔（i.p.）注射 CP（5mg/kg）和 CP（5mg/kg）加尼美舒利（20mg/kg/天，共 5 天）。实验结束时，对大鼠进行麻醉并监测血压和肾血流量（RBF），随后静脉内（i.v.）注射去甲肾上腺素（NE）。通过组织病理学和生物化学方法评估肾毒性。CP 导致 WKY 和 SHR 大鼠的基础 RBF 降低。它增加了尿素和肌酐的浓度以及肾相对重量，同时降低了 WKY 和 SHR 大鼠的体重。组织病理学检查显示 CP 导致 WKY 大鼠和 SHR 大鼠的肾脏损伤明显。单独使用尼美舒利治疗不会对上述任何测量指标产生任何显著变化。然而，尼美舒利加重了 SHR 大鼠 CP 诱导的肾组织损伤，但对 WKY 大鼠没有影响。结果表明，尼美舒利在 SHR 大鼠中加重了肾毒性的组织病理学指标，但在 WKY 大鼠中没有。
