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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 observe the toxicity of nitrofurantoin to SD rats through long-term toxicity test to evaluate the safety of nitrofurantoin. Methods: Sixty SD rats were randomly divided into 5 groups (blank control group, nitrofurantoin low dose group, nitrofurantoin high dose group, diethyl ester group, nitrofurazone group), 12 in each group. Body weight, food intake, urine output, hematological indexes, blood biochemical indexes, organ coefficient and organ histopathology were detected within 3 weeks respectively. Results: There were no significant differences in body weight, food intake, urine output and hematology between the two groups. Serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) (P <0.05). The levels of reticulocyte count (RC) and prothrombin time (PT) in the high-dose nitrofurantoin group were significantly higher than those in the high-dose nitrofurantoin group (P < <0.05) and BUN (P <0.01), and albumin (ALB) was significantly lower in nitrofurantin group than in nitrofurantin group. AST and BUN of blood biochemical indexes in diethyl ester group were significantly increased The coefficient of each organ in the rats was not significantly different from that in the control group. Histopathological examination revealed mild hypertrophy of myocardial cells, mild glomerular filtration membrane injury, Tubular epithelial cells swelling, diethyl ester group of glomerular filtration membrane and renal tubular epithelial cells were significantly damaged. Conclusion: Nitrofurantoin has a hemolysis effect at high dose, which has adverse effects on kidney, liver and heart. Nitrofurazone has no effect on every index of rats. Diethyl ester has an effect on kidney and liver damage.