摘要
目的:通过长期毒性试验,观察呋喃妥因对SD大鼠所发生的各种毒性反应,以评价呋喃妥因的安全性。方法:SD大鼠60只,雌雄各半,随机分为5组(空白对照组、呋喃妥因小剂量组、呋喃妥因大剂量组、二乙酯组、呋喃西林组),每组12只,灌胃给药3周内分别检测体重、食量、尿量、血液学指标、血液生化指标、脏器系数及脏器组织病理。结果:大鼠体重、食量、尿量、血液学12项指标均无显著性差异,血液生化指标中血清天门冬氨酸氨基转移酶(AST)和血尿素氮(BUN)均升高,总胆固醇(T-CHO)降低(P<0.05),呋喃妥因大剂量组血液学指标中网织红细胞计数(RC)和凝血酶原时间(PT)升高(P<0.05),血液生化指标中AST(P<0.05)和BUN(P<0.01)显著升高,白蛋白(ALB)显著降低,呋喃西林组各指标均无明显影响,二乙酯组血液生化学指标AST和BUN升高,ALB显著降低,各组大鼠的各脏器系数与对照组比均无显著性差异,病理组织学检查显示呋喃妥因大剂量组大鼠的心肌细胞轻度肥大,肾小球滤过膜有轻度损伤,肾近曲小管上皮细胞肿胀,二乙酯组对肾小球滤过膜及肾小管上皮细胞有明显损伤。结论:呋喃妥因大剂量有溶血作用,对肾、肝、心有不利作用,呋喃西林对大鼠各指标无影响,二乙酯对肾和肝有损伤作用。
Objective ：To study various kinds of toxic reaction of nitrofurantoin on SD rats via long - term toxicity test, so as to evaluate the safety of nitrofurantoin. Method： Sixty SD rats （30 males and 30 females） were randomly divided into 5 groups （blank control group,low and high dosage of nitrofurantoin group, diethylmaleate group, nitro- rural group, n = 12）. The weight, appetite, urine volume, haematological indexes, blood biochemical indexes, organ coefficient and histopathologic of organs of the mice were measured in 3 weeks of administration respectively. Results： Compared with control group, there was no significant difference in the weight, appetite, urine volume, haematological indexes, blood biochemical indexes, organ coefficient and histopathologie of organs of each medicine group （ P 〉 0. 05 ） ; In blood biochemical index, serum aspartate aminotransferase （AST） and blood urea nitrogen （BUN） were higher, total cholesterol （ T - CHO） was lower （ P 〈 0. 05 ）. In high dosage of nitrofurantoin group, retic- ulocyte count（RC） and prothrombin time（PT） of haematological indexes were higher（ P 〈0. 05 ）,blood biochemical indexes ： AST（ P 〈 0. 05 ） and BUN （ P 〈 0. 01 ） were significantly increased, ALB was significantly reduced. The ni- trofural group had no significant effect on each indexes. In diethylmaleate group, blood biochemical indexes：AST and BUN was increased, albumin（ALB）was significantly reduced. There was no significant difference in the organ coefficient of rats in each group compared with the control group. Histopathological examination showed mild hyper- trophy of myocardial cells,mild injury in the glomerular filtration membrane and kidney proximal tubule epithelial cells swelling in nitrofurantoin high - dose group rats. In addition, obvious damage on the glomerular filtration mem- brane and kidney tubular epithelial cells were observed in diethylmaleate group. Conclusion： Because of hemolysisinduced by large doses of nitrofurantoin, there was an adverse effect on the kidney,liver, heart. Nitrofurazone had no effect on various indicators of the rat. Diethylmaleate could damage kidney and liver.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2013年第1期7-11,共5页
Chinese Journal of Pharmaceutical Analysis
关键词
呋喃妥因
呋喃西林
二乙酯
长期毒性
血液生化指标
nitrofurantoin
nitrofural
diethylmaleate
long - term toxicity test
blood biochemical index
