新三嗪化合物纳川珠利的小鼠亚急性毒性试验

Subacute toxicity testing of a new triazines nitromezuril in mice

为评价新三嗪类抗球虫药物纳川珠利的安全性,选用100只昆明小鼠,连续30d分别灌服4.8、19.2、76.8mg/kg的药物,以纯水和空白溶剂为对照,通过临床观察、血液学分析、血液生化检测、脏器系数和病理学检查,系统地评估了该化合物对小鼠的亚急性毒性作用。结果显示,试验期间无小鼠死亡,在开始用药1周内,高剂量组小鼠有轻微临床毒性症状,2周后症状消失。试验过程中各组小鼠增重差异无统计学意义(P>0.05),长期高剂量给药后小鼠心和肝的脏器系数明显改变(P<0.05),血液红细胞、碱性磷酸酶、肌酐明显增高和葡萄糖、胆固醇、尿酸显著降低(P<0.05),高剂量组肝、肾小部分发生轻微水样变性、点状坏死等病理改变,停药15d后,碱性磷酸酶和尿酸水平与对照组差异有统计学意义(P<0.05)。提示纳川珠利长期大剂量使用可能存在肝、肾等轻微损伤的风险,但损伤是可逆的,停药后短期可逐渐恢复,临床使用相对安全。

To evaluate the safety of nitromezuril,a new benzeneacetonitrile agent,the subacute toxic effects on Kunming mice were evaluated.Mice were randomly assigned to 5 groups with 20 mice（half male and half female） in each group.The treatment conditions were employed as following：mice provided with 4.8 mg/（kg·d） marked low dose group,mice provided with 19.2 mg/（kg·d） marked middle dose group,mice provided with 76.8 mg/（kg·d） marked high dose group,mice provided with reverse osmosis marked control group,and mice provided with blank solvent marked blank group.Thirty days later,the effect on organs,the hematological and biochemical parameters were assessed.The results showed that all mice could tolerate these doses.The body weight gains of mice were not affected by the treatment.Histopathological examinations showed that significant changes（P0.05） in the heart and liver（hydropic degeneration,spotty necrosis） of mice were found in the high dose group.In addition,among the biochemical parameters stu-died,red blood cell,alkaline phosphatase（ALP）,and creatinine significantly increased（P0.05）,while glucose,cholesterol and uric acid（UA） significantly decreased（P0.05） in the high dose group.However,-15 days after withdrawal,the symptom mentioned above reduced with exception of ALP and UA.The ove-rall results indicated that nitromezuril had no subacute toxic effects in mice.