Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Muscat 123, Sultanate of Oman.
J Appl Toxicol. 2010 Jan;30(1):15-21. doi: 10.1002/jat.1465.
This work investigated the effect of N-acetylcysteine (NAC), on renal hemodynamics in cisplatin (CP)-induced nephrotoxicity in Wistar-Kyoto (WKY) rats. The animals were divided into four groups (n = 5 or 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) N-acetylcysteine (500 mg kg(-1) per day for 9 days), respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (5 mg kg(-1)) and an i.p. injection of CP (5 mg kg(-1)) together with i.p. NAC (500 mg kg(-1) per day for 9 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE) for measurement of renal vasoconstrictor responses. CP caused a significant reduction in renal blood flow but did not affect NE-induced renal vasoconstriction. In addition, CP significantly increased plasma concentrations of urea and creatinine and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and kidney relative weight. CP decreased body weight and creatinine clearance. Histopathologically, CP caused remarkable renal damage compared with control. NAC alone did not produce any significant change in any of the variables measured. However, NAC significantly ameliorated CP-induced hemodynamic, biochemical and histopathological changes. The concentration of platinum in the kidneys of CP ? NAC treated rats was less than in CP-treated rats by 37%. The results show that administration of i.p. NAC (500 mg kg(-1) per day for 9 days) reversed the renal hemodynamic changes as well as the biochemical and histopathological indices of CP-induced nephrotoxicity in WKY rats.
本研究旨在探讨 N-乙酰半胱氨酸（NAC）对顺铂（CP）诱导的 Wistar-Kyoto（WKY）大鼠肾毒性的肾血流动力学的影响。动物分为四组（n = 5 或 6）。第一组和第二组分别接受生理盐水（对照）和腹腔内（i.p.）N-乙酰半胱氨酸（500mg/kg，每天一次，共 9 天）治疗。第三组和第四组分别单次腹腔内注射 CP（5mg/kg）和 CP（5mg/kg），同时腹腔内注射 NAC（500mg/kg，每天一次，共 9 天）。实验结束时，麻醉大鼠，监测血压和肾血流量，然后静脉内（i.v.）注射去甲肾上腺素（NE），测量肾血管收缩反应。CP 导致肾血流量显著减少，但不影响 NE 诱导的肾血管收缩。此外，CP 显著增加了血浆尿素和肌酐浓度以及尿 N-乙酰-β-D-氨基葡萄糖苷酶（NAG）活性和肾脏相对重量。CP 降低了体重和肌酐清除率。组织病理学检查显示，CP 导致的肾脏损伤明显比对照组严重。NAC 单独使用不会引起任何测量变量的显著变化。然而，NAC 显著改善了 CP 诱导的血流动力学、生化和组织病理学变化。CP-NAC 治疗大鼠肾脏中的铂浓度比 CP 治疗大鼠低 37%。结果表明，腹腔内给予 NAC（500mg/kg，每天一次，共 9 天）可逆转 CP 诱导的 WKY 大鼠肾毒性的肾血流动力学变化以及生化和组织病理学指标。
