中国药物警戒 ›› 2022, Vol. 19 ›› Issue (6): 635-640.
DOI: 10.19803/j.1672-8629.2022.06.11

• 何首乌质量及安全性评价专栏（一） • 上一篇    下一篇

大黄素体内遗传毒性风险评价

文海若, 王亚楠△, 姜华, 王雪, 汪祺#, 马双成*   

  1. 中国食品药品检定研究院,北京 100050
  • 收稿日期:2022-02-25 出版日期:2022-06-15 发布日期:2022-06-13
  • 通讯作者: * 马双成,男,博士,研究员,中药民族药物质基础与质量安全评价研究。E-mail：sansan8251@sina.com;#为共同通信作者。
  • 作者简介:文海若,女,博士,研究员,遗传毒理。△为并列第一作者。
  • 基金资助:
    国家自然科学基金资助项目（81973476）; 重大新药创制国家科技重大专项2018年度（2018ZX09201017）

In vivo genotoxic risk assessment of emodin

WEN Hairuo, WANG Yanan△, JIANG Hua, WANG Xue, WANG Qi#, MA Shuangcheng*   

  1. National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2022-02-25 Online:2022-06-15 Published:2022-06-13

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摘要： 目的 评价连续28 d灌胃给予小鼠大黄素,小鼠体内遗传毒性风险。方法 KM小鼠连续28 d灌胃重复给予大黄素并设28 d恢复期。分别于给药前、首次给药后第14、 28、 42和56 天采集外周血检测网织红细胞和总红细胞的突变率,以及网织红细胞占总红细胞的百分率;末次给药后采集肝、肾、外周血开展彗星试验,分析每只动物至少100个细胞的尾DNA百分含量;末次给药后制备骨髓细胞样本,计算嗜多染红细胞占总红细胞的百分率以及嗜多染红细胞的微核发生率。结果 与溶媒对照组（0.5%羧甲基纤维素钠）相比,300 mg·kg-1及以下给药组连续给药28 d未见Pig-a基因突变率增加。肾细胞彗星试验结果显示,与溶媒对照组（0.5%羧甲基纤维素钠）相比,所设浓度范围内各组尾DNA百分含量显著升高（P<0.01,P<0.001）。骨髓微核试验显示所设浓度范围内未见微核率的升高。结论 连续28 d经口灌胃给予小鼠大黄素后,主要作用部位为肾脏;当前试验条件下,大黄素未导致小鼠体内Pig-a基因突变发生率和骨髓微核发生率增加,但可导致肾脏细胞DNA损伤。

关键词: 何首乌, 大黄素, 遗传毒性, KM小鼠, Pig-a, 彗星试验, 微核试验, 风险评价

Abstract: Objective To evaluate the in vivo genotoxic risk of emodin administered by oral gavage to mice for 28 consecutive days. Methods KM mice were repeatedly administered with emodin for 28 consecutive days by oral gavage, followed by a recovery period of 28 days. Peripheral blood was collected before administration, 14, 28, 42 and 56 days after the first administration to detect the mutation rate of reticulocytes and total red blood cells as well as the percentage of reticulocytes in total red blood cells. Liver, kidney and peripheral blood was collected after the last administration to carry out the comet test. The percentage of tail DNA of at least 100 cells in each animal was analyzed. Samples of bone marrow cells were prepared after the last administration, and polychromatic erythrocytes as well as the incidence of micronuclei in polychromatic erythrocytes were calculated. Results Compared with the vehicle control group (0.5% carboxymethylcellulose sodium), the Pig-a gene mutation rate in groups dosed with emodin was not increased after 28 consecutive days of administration of 300 mg·kg-1 or under. Compared with the vehicle control group (0.5% carboxymethylcellulose sodium), the percentage of tail DNA of kidney cells in groups dosed with emodin was significantly increased with a dose-response pattern (P<0.01, P<0.001）. Data on bone marrow micronucleus test showed no increase in the rate of micronuclei within the current dose range. Conclusion After 28 consecutive days of oral administration of emodin to mice, the main action site of emodin in mice is found to be the kidney. Under current conditions, emodin does not increase in the rate of Pig-a gene mutation or in the incidence of bone marrow micronuclei in mice, but it could lead to DNA damage to kidney cells.

Key words: Polygonum multiflorum, emodin, genotoxicity, KM mice, Pig-a, comet assay, micronucleus assay, risk assessment

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