阿司匹林丁香酚酯对大鼠的急性毒性研究

发布时间：2019-03-12 12:34

【摘要】：试验旨在评价阿司匹林丁香酚酯(aspirin eugenol ester,AEE)对大鼠的急性毒性,了解AEE毒性特点及可能的毒性靶器官,并全面地分析大鼠的致死原因。试验按照改良寇氏法进行,预试验选取50只大鼠,雌雄各半,分为5组,测定绝对致死量(LD100)和最大非致死量(LD0)。根据预试验结果,将80只健康大鼠,雌雄各半,随机平均分为7个药物组(剂量分别为2.62、3.25、4.03、5.00、6.20、7.69和9.53g/kg)和1个对照组(给予0.5%的羧甲基纤维素钠(CMC-Na)进行正式试验。灌胃给药,观察并记录大鼠给药后的临床症状及体重变化。给药14d后,统计各剂量组大鼠的死亡时间及总死亡数,并计算AEE的半数致死量(LD50)及其95%可信限。同时对死亡大鼠及时进行剖检,将具有病变的组织用10%的甲醛溶液固定,以进行病理学分析。结果显示,AEE对大鼠口服的LD50是5.95g/kg,且LD50的95%可信限为5.30~6.68g/kg。对大鼠的死亡时间进行分析可得出,当口服AEE的剂量大于4.03g/kg时,其死亡时间主要集中在染毒后的48~96h内。大鼠染毒后3d内,体重呈下降趋势,常规饲养第5天开始,大鼠体重可逐渐恢复。病理学检查分析发现,AEE的剂量在5.00g/kg以上时,对大鼠的肝脏、肾脏和胃肠道有明显损伤。根据外源化学物急性毒性分级(WHO)可知,AEE为实际无毒化合物,AEE对大鼠毒性靶器官主要是肝脏、肾脏和胃肠道。
[Abstract]:The aim of the experiment was to evaluate the acute toxicity of aspirin eugenol ester (aspirin eugenol ester,AEE) to rats, to understand the toxicity characteristics and possible target organs of AEE, and to analyze the causes of death in rats. 50 rats, half male and half female, were divided into 5 groups. Absolute lethal dose (LD100) and maximum non-lethal dose (LD0) were measured. According to the results of the pre-test, 80 healthy rats, half male and half female, They were randomly divided into seven drug groups (2.62, 3.25, 4.03, 5.00, 6.20, 7.69 and 9.53g/kg, respectively) and one control group (0.5% sodium carboxymethyl cellulose (CMC-Na) for formal trial. The clinical symptoms and body weight changes of rats were observed and recorded by intragastric administration. After 14 days of administration, the time of death and the total number of deaths of rats in each dose group were counted, and the half lethal dose (LD50) of AEE and its 95% confidence limit were calculated. At the same time, the dead rats were examined in time, and the tissues with pathological changes were fixed with 10% formaldehyde solution for pathological analysis. The results showed that the oral LD50 of AEE to rats was 5.95g / kg, and the 95% confidence limit of LD50 was 5.30g / 6.68g / kg 路kg ~ (- 1). The results showed that when the dose of AEE was greater than that of 4.03g/kg, the time of death was mainly within 48 hours after exposure. The body weight of the rats decreased within 3 days after exposure. From the 5th day of routine feeding, the body weight of the rats could gradually recover. Pathological analysis showed that when the dose of AEE was above 5.00g/kg, the liver, kidney and gastrointestinal tract of rats were obviously damaged. According to the acute toxicity grade (WHO) of exogenous chemicals, AEE is a practical non-toxic compound. The target organs of AEE toxicity to rats are mainly liver, kidney and gastrointestinal tract.
【作者单位】：中国农业科学院兰州畜牧与兽药研究所农业部兽用药物创制重点实验室甘肃省新兽药工程重点实验室;
【基金】：国家自然科学基金(31572573) 中国农业科学院科技创新工程(CAAS-ASTIP-2014-LIHPS-02)
【分类号】：S859.7

【参考文献】