二巯丁二酸对小鼠的急性毒性作用

Acute toxicity of meso-2,3-dimercaptosuccinic acid on mice

目的探讨二巯丁二酸(DMSA)对小鼠的急性毒性作用。方法20只昆明小鼠,雌雄各半,体质量(21.2±2.3)g,适应性喂养3 d,按体质量随机分为对照组和实验组,给药前禁食12 h,实验组每只小鼠于24 h内分4次经口给予DMSA 160 mg,对照组给予等体积的去离子水,观察1周,然后摘除眼球取血,置于肝素化试管,5 000 r/min,离心5 min,取血浆;处死小鼠,取其脑、心脏、肝脏和肾脏,0.9%氯化钠溶液清洗。测定抗氧化酶系统、过氧化产物、血尿素氮、血肌酐及氨基转移酶水平。结果(1)试验观察期内小鼠出现消化道症状,进食减少.体质量降低,腹腔轻度积水,此外未见其他明显中毒症状;(2)脑组织、肝脏和肾脏超氧化物歧化酶(SOD)活性降低,但差异无统计学意义(P>0.05),谷胱甘肽过氧化物酶(GSH-PX)活性明显降低(P<0.01),肝脏丙二醛(MDA)显著性升高(P<0.01);(3)血尿素氮和肌酐水平显著性升高(P<0.001);血氨基转移酶升高(P<0.001),而肝肾氨基转移酶无显著性变化。结论二巯丁二酸抑制机体抗氧化系统,对肝脏和肾脏具有毒性作用。

Objective To explore acute toxicity of succimer on mice. Methods Twenty Kunming mice（10 males and 10 females） weighting approximately （21.2±2.3）g were acclimatized for 3 days prior to dosing, then were divided into control group and experiment group with 10 mice in each group according to body weight. Fasted for 12 hours,the mice in experiment group received intragastric administration of 160mg DMSA in deionized water in 24 hours,and the control group received the same volume of deionized water, and then they were observed for 7 days. Blood was collected into heparinized-tubes by removal of eyeball. All mice were sacrificed and brain, heart,liver and kidney were removed and washed with normal saline. The activity or amount of BUN, Scr, AST, ALT, SOD, GSH-PX and MDA were analyzed. Results （1） Given 160mg DMSA in 24 hours, gastrointestinal symptoms were main side effects. During the observation, experiment group lost weight due to the decrease of food-intake, and some mice had slight hydroabdomen. （2）High dose of DMSA caused a significant inhibition of GSH-PX（ P 〈 0.01 ）. The activity of SOD was inhibited, but it had no statistical significance（P〉 0.05 ）. The hepatic cell was damaged according to the significant raise of MDA in liver（P〈 0.01 ）. （3）The amount of BUN and Scr significantly rose due to the damage of kidney （ P 〈 0.001 ）. The aminopherase rose significantly in blood（ P 〈 0.001 ）, but not in liver and kidney （ P 〉 0.05）,which was related to acute toxicity on liver. Conclusion Succimer could inhibit the antioxidant systems and could do damage to liver and kidney.