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期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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SD大鼠重复给予大黄素甲醚肝毒性与遗传毒性研究

Hepatotoxicity and genotoxicity study of physcion in SD rats with repeated doses

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (10):1719-1726
DOI: 10.16155/j.0254-1793.2017.01.01
-----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。

-----英文摘要:---------------------------------------------------------------------------------------

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·kg-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.

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