摘要
目的:综合重复给药毒性试验和遗传毒性试验,对大黄素甲醚研究潜在肝毒性及遗传毒性进行评价。方法:雄性Spargue-Dawley(SD)大鼠随机分为对照组(0.5%羧甲基纤维素钠)及大黄素甲醚低(6.5 mg·kg^(-1))、中(65 mg·kg^(-1))和高剂量组(650 mg·kg^(-1)),连续14 d经口灌胃给药;平行设甲磺酸乙酯(200 mg·kg^(-1))遗传毒性试验阳性对照组。观察动物临床症状,分析体质量、血清生化指标、肝脏质量及病理学指标变化,并开展微核试验及彗星试验。结果:连续14 d给予SD大鼠大黄素甲醚,未见明确的与大黄素甲醚有关的肝毒性表现,且未检出其存在诱导SD大鼠肝细胞染色体损伤DNA断裂的作用。结论:当前试验条件下大黄素甲醚未见毒副反应剂量为650 mg·kg^(-1)。本研究为对大黄素甲醚潜在肝毒性的初步探索,建议延长给药时间并增加动物数量,以进一步明确其体内毒性。
Objective：To evaluate the potential hepatotoxicity and genotoxicity of physcion by performing jointed repeated-dose toxicity study and genotoxicity study.Methods：Male Sprague-Dawley （SD） rats were randomly divided into control （0.5% sodium carboxymethyl cellulose）, low dose （6.5 mg·kg^-1 physcion）, medium dose （65 mg·k^g-1 physcion） and high dose （650 mg·kg^-1 physcion） groups.Administration was through oral gavage for consecutive 14 days.A positive control group for genotoxicity study were used in parallel and administrated with ethyl methanesulfonate （200 mg·kg^-1）.Clinical symptoms, body weight, serum biochemical examinations data, liver weight and histopathological examination results were analyzed, and the micronucleus test and comet assay were performed.Results：No definite hepatotoxicity associated with physcion were found in SD rats with repeated doses for consecutively 14 days.No chromosome damage nor DNA breakage effect on the hepatocyte was detected.Conclusion：Under the current condition, no observable adverse effect level for physcion is estimated at 650 mg·kg^-1.As a preliminary exploration of the potential hepatotoxicity of physcion, a study with extended administration period and increased animal number is recommended for identifying its in vivo toxicity.
作者
任璐
文海若
吕建军
宋捷
王超
苗玉发
黄芝瑛
汪祺
REN Lu;WEN Hai-ruo;LV Jian-jun;SONG Jie;WANG Chao;MIAO Yu-fa;HUANG Zhi-ying;WANG Qi(School of Phamaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China;National Center for Safety Evaluation of Drugs,National Institutes for Food and Drug Control,Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs,Beijing 100176,China;Institute for Control of Chinese Traditional Medicine and Ethnic Medicine,National Institutes for Food and Drug Control,Beijing 100050,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2018年第10期1719-1726,共8页
Chinese Journal of Pharmaceutical Analysis
基金
国家自然科学基金资助项目(81503347)
国家“重大新药创制”科技重大专项(2015ZX09501004-002)
关键词
大黄素甲醚
大黄蒽醌类化合物
何首乌
SD大鼠
重复给药毒性
肝毒性
用药安全
微核试验
彗星试验
physcion
rhubarb anthraquinones compounds
Polygoni Muhifiori Radix
SD rat
repeated-dose toxicity
hepatoxicity
drug safety
micronucleus test
comet assay
