N-acetyleysteine ameliorates lithium-induced renal failure in rats
N-acetyleysteine ameliorates lithium-induced renal failure in rats
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DOI：
10.1093/ndt/gfh573
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发表时间：
2005-01-01
影响因子：
6.1
通讯作者：
Averbukh, Z
中科院分区：
文献类型：
--
作者：
Efrati, S;Averbukh, M;Averbukh, Z
背景资料。长期的锂治疗可能会导致人类和实验动物肾功能的进行性恶化。N-乙酰半胱氨酸(N-Acetylcysteine，NAC)已被证明能有效地预防低灌注量和毒素所致的肾功能衰竭，但其对锂肾毒性的影响尚未得到评估。本研究的目的是观察NAC对锂诱导的大鼠肾功能衰竭的可能的肾脏保护作用。40只SD大鼠采用5周方案诱导中度肾功能衰竭，其中包括饮用水中3周的氯化锂灌胃。动物被随机分成两组，每天两次腹腔注射10 mg/kg NAC或生理盐水。6周后用~(99m)Tc二乙三胺五乙酸法测定肾小球滤过率(GFR)，并测定血肌酐、血尿素氮(BUN)和24小时尿蛋白定量及渗透压。切取肾脏进行病理检查。锂方案结束时，NAC治疗组肾小球滤过率显著高于对照组，分别为0.92+/-0.35vs0.56+/-0.25ml/min/100g，P=0.002。NAC治疗组血清肌酐和BUN分别为1.009+/-0.107和1.143+/-0.118 mg/dl，P=0.001；光镜下观察，NAC组肾小管坏死率和管腔梗阻百分率明显低于对照组，分别为P=0.002和P=0.007。NAC治疗对锂诱导的大鼠肾功能衰竭有保护作用。
Background. Prolonged lithium treatment may induce progressive deterioration of renal function in humans and experimental animals. N-Acetylcysteine (NAC) has been shown to be effective in the prevention of hypoperfusion and toxin-induced renal failure, but its effect on lithium nephrotoxicity has not been evaluated yet. The purpose of this study was to examine a possible renoprotective effect of NAC against lithium-induced renal failure in a rat model.Methods. Moderate renal failure was induced in 40 Sprague-Dawley rats using a 5 week protocol including 3 weeks of lithium chloride administration in the drinking water. The animals were divided randomly into two equal groups receiving either 10 mg/kg NAC or saline by two daily intraperitoneal injections. In week 6, the glomerular filtration rate (GFR) was assessed by (99m)Technetium diethylene triaminepenta-acetic acid, and serum creatinine, blood urea nitrogen (BUN) and 24h urinary protein and osmolarity were measured. Kidneys were excised for pathological evaluation.Results. At the end of the lithium protocol, the GFR was significantly higher in the NAC-treated group compared with the control group, 0.92 +/- 0.35 vs 0.56 +/- 0.25 ml/min/100g, respectively, P = 0.002. Serum creatinine and BUN were also significantly lower in the NAC-treated group 1.009 +/- 0.107 vs 1.143 +/- 0.118 mg/dl, P=0.001, and 83.9 +/- 6.8 vs 88.95 +/- 7.1 mg/dl, P=0.28, respectively. The percentages of tubular necrosis and tubular lumen obstruction, evaluated by light microscopy, were significantly lower in the NAC-treated group, P = 0.002 and P = 0.007, respectively.Conclusions. NAC treatment has a renoprotective effect against lithium-induced renal failure in a rat model.