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落新妇苷的非临床安全性:一项为期4周的大鼠口服毒性研究,包括遗传毒性、染色体畸变和哺乳动物微核试验。

Nonclinical safety of astilbin: A 4-week oral toxicity study in rats with genotoxicity, chromosomal aberration, and mammalian micronucleus tests.

作者信息

Gao Yonglin, Li Chunmei, Wang Yunzhi, Liu Yunguo, Li Guisheng, Fan Xiaochen, Li Yanshen, Tian Jingwei, Lee Albert W

机构信息

School of Life Sciences, Yantai University, Yantai, 264005, PR China.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China.

出版信息

Food Chem Toxicol. 2017 Sep;107(Pt A):1-9. doi: 10.1016/j.fct.2017.06.024. Epub 2017 Jun 15.

DOI:10.1016/j.fct.2017.06.024
PMID:28624472
Abstract

Astilbin is an active flavonoid compound isolated from Rhizoma Smilacis Glabrae. It has been widely used as an anti-hepatic, anti-arthritic, and anti-renal injury agent. However, its safety has not yet been established. The objective of this study was to evaluate 4-week repeated oral toxicity and genotoxicity of astilbin. We examined oral toxicity in Sprague-Dawley rats after daily oral administration of astilbin at 50, 150, and 500 mg/kg for 4 weeks. Negative control animals received the same volume of the solvent. Astilbin administration did not lead to death, body weight gain, food consumption, or adverse events. There were no significant differences in toxicity between the astilbin and control group; we observed no toxic effects on hematological or urinalysis parameters, biochemical values, organ weight, or histopathological findings. We assessed the genotoxicity of astilbin with the Ames test (TA97a, TA98, TA100, TA102, and TA1535), chromosomal aberration assay (using Chinese hamster ovary cells), and mammalian micronucleus test (in mice). We found no genotoxicity in any tested strains. The no-observed-adverse-effect level (NOAEL) for astilbin in the 4-week repeated oral toxicity study in rats was greater than 500 mg/kg body weight/day, regardless of gender. Results also suggested that astilbin does not have genotoxicity potential.

摘要

落新妇苷是从光叶菝葜根茎中分离出的一种活性黄酮类化合物。它已被广泛用作抗肝、抗关节炎和抗肾损伤药物。然而,其安全性尚未确定。本研究的目的是评估落新妇苷4周重复口服毒性和遗传毒性。我们在Sprague-Dawley大鼠中每日口服50、150和500 mg/kg落新妇苷,持续4周,以检测口服毒性。阴性对照动物给予相同体积的溶剂。给予落新妇苷未导致死亡、体重增加、食物消耗或不良事件。落新妇苷组和对照组在毒性方面无显著差异;我们未观察到对血液学或尿液分析参数、生化值、器官重量或组织病理学结果的毒性作用。我们用Ames试验(TA97a、TA98、TA100、TA102和TA1535)、染色体畸变试验(使用中国仓鼠卵巢细胞)和哺乳动物微核试验(在小鼠中)评估落新妇苷的遗传毒性。我们在任何测试菌株中均未发现遗传毒性。在大鼠4周重复口服毒性研究中,落新妇苷的未观察到有害作用水平(NOAEL)大于500 mg/kg体重/天,无论性别如何。结果还表明落新妇苷没有遗传毒性潜力。

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