度洛西汀对小鼠急性毒性及遗传毒性的研究

目的:探讨度洛西汀对成年雄性小鼠的急性毒性及遗传毒性。方法:采用小鼠急性毒性试验观察致死率及半数致死量(LD₅₀)。采用小鼠骨髓微核试验、小鼠精子畸变试验及生殖与淋巴器官重量指数检测方法,将小鼠均分为6组,即阴性对照组、阳性对照组,度洛西汀1、2、3和4组(分别给予度洛西汀5、10、20和40 mg/kg),观察度洛西汀不同剂量对小鼠精子畸变率、骨髓微核率及生殖与淋巴器官重量指数的影响。结果:度洛西汀急性毒性试验结果表明,灌胃给予度洛西汀的LD₅₀为188.3 mg/kg。微核试验与精子畸变试验结果表明,度洛西汀灌胃剂量为5、10和20 mg/kg时(度洛西汀1、2和3组)均未诱发小鼠精子畸变率和骨髓微核率的改变,与阴性对照组相比,差异均无统计学意义(P>0.05);度洛西汀4组小鼠的精子畸变率、骨髓微核率均高于阴性对照组,差异有统计学意义(P<0.05)。度洛西汀1、2、3和4组小鼠的生殖与淋巴器官重量指数与阴性对照组相比,差异均无统计学意义(P>0.05)。结论:灌胃给予度洛西汀的LD₅₀为188.3 mg/kg,安全性高。度洛西汀以5、10和20 mg/kg的剂量灌胃对小鼠无生殖与遗传毒性,当灌胃剂量达到40 mg/kg时对雄性小鼠有轻微的潜在遗传毒性。

Acute Toxicity and Genotoxicity of Duloxetine in Mice

OBJECTIVE:To probe into the acute toxicity and genotoxicity of duloxetine in adult male mice.METHODS:Acute toxicity test in mice was used to observe the fatality rate and the lethal dose 50(LD₅₀).According to bone marrow micronucleus test,sperm malformation test and reproductive and lymphatic organ mass index test,all mice were divided into 6 groups,including negative control group,positive control group,duloxetine group 1,2,3 and 4(duloxetine 5,10,20 and 40 mg/kg were given respectively).The effects of different doses of duloxetine on sperm malformation rate,bone marrow micronucleus rate and reproductive and lymphatic organ mass index of mice.RESULTS:The results of acute toxicity test of duloxetine showed that the LD₅₀of duloxetine administered intragastrically was 188.3 mg/kg.The results of micronucleus test and sperm malformation test showed that 5,10 and20 mg/kg of duloxetine administered intragastrically(duloxetine group 1,2 and 3)did not induce the change of sperm malformation rate and bone marrow micronucleus rate,and there was no statistical significance compared with the negative control group(P>0.05).The sperm malformation rate and bone marrow micronucleus rate in duloxetine group4 were higher than those in negative control group,with statistically significant difference(P<0.05).Compared with the negative control group,there was no significant difference in reproductive and lymphatic organ mass indexes of duloxetine group 1,2,3 and 4(P>0.05).CONCLUSIONS:The LD₅₀of duloxetine was 188.3 mg/kg by intragastric administration,which is highly safe.Duloxetine showed no reproductive and genotoxicity in mice administered at 5,10 and 20 mg/kg,but had slight potential genetic toxicity in male mice when administered at 40 mg/kg.