类叶升麻苷大鼠安全性评价

doi:10.19803/j.1672-8629.20220344

摘要/Abstract

摘要： 目的通过单次给药和重复给药毒性试验,初步评价类叶升麻苷的安全性,为深入全面开展其安全性评价奠定了基础。方法单次给药毒性试验,SD大鼠随机分为溶媒对照组和给药组（5 000 mg·kg^-1）,经口单次给药,观察并记录14 d内大鼠一般临床症状、死亡情况、体重;对主要脏器进行肉眼观察。重复给药毒性试验,SD大鼠随机分为溶媒对照组,类叶升麻苷低（100 mg·kg^-1）、中（500 mg·kg^-1）、高（2 000 mg·kg^-1）剂量组,每组30只,连续给药28 d,恢复28 d,观察并检测一般临床症状、体重、摄食量、尿常规等相关指标。结果单次给药毒性试验中各动物无死亡、无异常、与溶媒对照组相比,体重差异无统计学意义（P>0.05）,脏器组织无肉眼可见病变。重复给药毒性试验中,与溶媒对照组相比,大鼠体重、摄食量、凝血指标、脏器湿重及系数差异无统计学意义（P>0.05）;对血液学、肝功能和肾功能无毒理学影响,高剂量组脏器组织未见明显给药相关组织病理学改变;高剂量组雌性动物尿常规中出现白细胞、酮体阳性检出率偏高（P<0.05或P<0.01）,存在可逆性。结论单次给药毒性试验中,类叶升麻苷单次给药最大耐受剂量（MTD）>5 000 mg·kg^-1,重复给药毒性试验中,类叶升麻苷无明显毒性反应剂量（NOAEL）为500 mg·kg^-1。

关键词: 类叶升麻苷, SD大鼠, 毒性试验, 可逆性改变, 最大耐受剂量, 毒性

Abstract: Objective To preliminarily evaluate the safety of acteoside through toxicity tests of single and repeated dose, thus laying the foundation for in-depth and comprehensive safety evaluation. Methods Single dose toxicity test: SD rats were randomly divided into a solvent control group and a medication group(5 000 mg·kg^-1), and were administered orally in single dose. The general clinical symptoms,mortality,and weight of rats within 14 days were observed and recorded,and the main organs were visually observed.Repeated dose toxicity test: SD rats were randomly divided into a solvent control group, and acteoside low (100 mg·kg^-1), medium (500 mg·kg^-1), and high dose group(2 000 mg·kg^-1), 30 in each group, and were continuously administered for 28 days and recoverded for 28 days. Their general clinical symptoms, body weight, food intake, urine routine, and other related indicators were observed and tested. Results The single dose toxicity test results showed that compared with the solvent control group, there were no deaths or abnormalities in rats; there was no statistically significant difference in body weight (P>0.05), and there were no visible lesions in organ tissues. The repeated toxicity test results showed that compared with the solvent control group, there was no statistically significant difference in body weight, food intake, coagulation indicators, organ wet weight and organ coefficient of rats(P>0.05). There was no toxicological effect on hematology, liver function and kidney function, and there was no obvious histopathology change related to drug administration in the high dose group; the positive detection rate of white blood cells and ketone bodies in the urine routine of female animals in the high-dose group was relatively high (P<0.05 or P<0.01), indicating reversibility. Conclusion In the single dose toxicity test, the maximum tolerated dose (MTD) of single dose for acteoside was greater than 5000 mg·kg^-1, and in the repeated dose toxicity test, the no observed adverse effect level (NOAEL) of acteoside was 500 mg·kg^-1.

Key words: acteoside, SD rats, toxicity test, reversible changes, maximum tolerated(MTD), toxicity

中图分类号:

R994.1

聂雨楠, 张丽, 邵明香, 高莉, 闫明. 类叶升麻苷大鼠安全性评价[J]. 中国药物警戒, 2023, 20(7): 758-762.

NIE Yunan, ZHANG Li, SHAO Mingxiang, GAO Li, YAN Ming. Rats safety evaluation of acteoside[J]. Chinese Journal of Pharmacovigilance, 2023, 20(7): 758-762.

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