N-acetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity
N-acetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity
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DOI：
10.1002/jat.1465
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Ali, Badreldin H.
中科院分区：
文献类型：
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作者：
Abdelrahman, Aly M.;Al Salam, Suhail;Ali, Badreldin H.
本研究观察了N-乙酰半胱氨酸（NAC）对顺铂（CP）肾毒性大鼠肾血流动力学的影响。将动物分为四组（n = 5或6）。第一组和第二组接受生理盐水（对照）和腹膜内（i. p.）N-乙酰半胱氨酸（500 mg kg（-1）/天，持续9天）。第三组和第四组给予单次腹膜内（i. p.）注射CP（5 mg kg（-1））和腹膜内注射CP（5 mg kg（-1））和腹膜内注射NAC（500 mg kg（-1）/天，共9天）。在实验结束时，将大鼠麻醉并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）以测量肾血管收缩反应。CP引起肾血流量显着减少，但不影响NE诱导的肾血管收缩。此外，CP显著增加尿素和肌酐的血浆浓度和尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）活性和肾脏相对重量。CP降低体重和肌酐清除率。组织病理学上，CP组与对照组相比，肾损害明显。NAC单独没有产生任何显着变化的任何变量测量。然而，NAC显着改善CP引起的血流动力学，生化和组织病理学变化。CP + NAC处理大鼠肾脏中的铂浓度比CP处理大鼠低37%。结果表明，腹腔注射NAC（500 mg/kg/d，连续9天）可逆转CP所致WKY大鼠肾毒性的血液动力学改变以及生化和组织病理学指标。版权所有（C）2009约翰威利父子有限公司
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. Copyright (C) 2009 John Wiley & Sons, Ltd.