中国药物警戒 ›› 2018, Vol. 15 ›› Issue (4): 205-209.

• 过敏原非临床安全性评价专栏 • 上一篇    下一篇

5-羟甲基糠醛的急性毒性和细胞毒性研究

林琳1, 林铌1,2, 凌亚豪1, 李恩灿1, 范潇予1, 林生3, 臧清策3, 贺玖明3, 靳洪涛1,4,*   

  1. 1中国医学科学院北京协和医学院药物研究所新药安全评价研究中心,北京100050;
    2首都医科大学,北京100069;
    3中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京 100050;
    4北京协和建昊医药技术开发有限责任公司,北京100176
  • 收稿日期:2018-05-29 修回日期:2018-05-29 出版日期:2018-04-20 发布日期:2018-05-29
  • 通讯作者: 靳洪涛,男,副研究员,药物安全性评价及药物毒性作用机制。E-mail：jinhongtao@imm.ac.cn
  • 作者简介:林琳,女,在读硕士,药物安全性评价。
  • 基金资助:
    国家自然科学基金（81773996）：小分子物质5-HMF及其二聚体OMBF作为变应原的毒性与机制研究; 北京协和医学院“协和青年科研基金”（3332015135）：5-HMF及其聚合物的免疫毒性及机制探索研究

Study on Acute Toxicity and Cytotoxicity of 5-Hydroxymethylfurfural

LIN Lin1, LIN Ni1,2, LING Ya-hao1, Li En-can1, Fan Xiao-Yu1, LIN Sheng3, ZANG Qing-ce3, HE Jiu-ming3, JIN Hong-tao1,4,*   

  1. 1New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
    2Capital Medical University, Beijing 100069, China;
    3State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
    4Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd, Beijing 100176, China
  • Received:2018-05-29 Revised:2018-05-29 Online:2018-04-20 Published:2018-05-29

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摘要： 目的 考察5-羟甲基糠醛（5-HMF）对ICR小鼠的急性毒性及其对肥大细胞模型RBL-2H3和P815细胞的毒性。方法 用8种不同剂量的5-HMF溶液对ICR小鼠进行尾静脉给药,每日观察小鼠行为情况,测定小鼠体重,记录死亡数,并计算半数致死量（LD50）,观察期结束进行病理学检查;采用MTT法测定5-HMF溶液对RBL-2H3细胞和P815细胞的毒性影响,并计算IC50。结果 小鼠尾静脉给药后低剂量出现共济失调、强直性抽搐等现象,随着剂量升高,出现以上现象频率升高;在体重方面,最高剂量雄性给药后d1到恢复期结束d14,与对照组相比体重显著降低（P <0.01）,雌鼠给药后d1~d14,体重比对照组显著降低（P <0.01）,次高剂量雌鼠给药后d1、d11、d14体重有所减低（P <0.05）,d4~d7显著降低（P <0.01）;存活动物组织病理学检查结果提示5-HMF组诊断为慢性进行性肾病,利用Bliss法计算小鼠ICR急性毒性LD50为871.12 mg·kg-1;利用MTT法测定5-HMF对于肥大细胞RBL-2H3和P815的IC50分别为4.96 mM和7.43 mM。结论 5-HMF具有一定的急性毒性,LD50为871.12 mg·kg-1,毒性靶器官为肾脏。对两种细胞的IC50分别为4.96 mM和7.43 mM,上述结果为该物质的安全应用及其对肥大细胞的脱颗粒作用深入研究提供了参考数据。

关键词: 5-羟甲基糠醛（5-HMF）, 急性毒性, 细胞毒性, 肥大细胞

Abstract: Objective To investigate the acute toxicity of 5-hydroxymethylfurfural(5-HMF) on ICR mice and cytotoxicity on mast cell RBL-2H3 and P815. Methods ICR mice received tail vein injection of 8 different doses of 5-HMF. The mice were observed daily to record the number of death and body weight, then 50 % lethal dose of (LD50) was counted. Pathological examination was completed at the end of the observation period. The cytotoxicity of 5-HMF on mast cell: RBL-2H3 and P815 was measured by MTT assay and 50 % inhibitory concentration (IC50) was calculated. Results Ataxia, tonic convulsions and other phenomena appeared in low doses, and with the dose increasing the frequency of above phenomenon increased. 5-HMF significantly decreased the weight of all groups from d1~d14 compared with control group(P <0.01) and the LD50 value was 871.12 mg·kg-1 using Bliss method based on the mortality rate. Pathological examination showed that mice had chronic progressive nephropathy in all doses. The IC50 of 5-HMF solution on RBL-2H3 and P815 was respectively 4.96 mM and 7.43 mM. Conclusion 5-HMF has acute toxicity with LD50 871.12 mg·kg-1, and kidney is the toxic target organ. IC50 in RBL-2H3 and P815 is 4.96 mM and 7.43 mM respectively. It provided the experimental basis for the degranulation of mast cells and theoretical basis for its quality control and further safety research.

Key words: 5-hydroxymethylfurfural(5-HMF), acute toxicity, cytotoxicity, mast cell

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