对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用

史丰收, 赵潺, 王聪, 李雅倩, 余梦圆, 郑君, 李萍, 李贺, 商静静, 顾凌郡, 陈云霞, 苏宁. 对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用[J]. 生态毒理学报, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001
引用本文: 史丰收, 赵潺, 王聪, 李雅倩, 余梦圆, 郑君, 李萍, 李贺, 商静静, 顾凌郡, 陈云霞, 苏宁. 对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用[J]. 生态毒理学报, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001
Shi Fengshou, Zhao Chan, Wang Cong, Li Yaqian, Yu Mengyuan, Zheng Jun, Li Ping, Li He, Shang Jingjing, Gu Lingjun, Chen Yunxia, Su Ning. Inhibitory Effects of Propylparaben and Butylparaben on CYP450 Enzyme Activity in Human and Rat Liver Microsomes[J]. Asian journal of ecotoxicology, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001
Citation: Shi Fengshou, Zhao Chan, Wang Cong, Li Yaqian, Yu Mengyuan, Zheng Jun, Li Ping, Li He, Shang Jingjing, Gu Lingjun, Chen Yunxia, Su Ning. Inhibitory Effects of Propylparaben and Butylparaben on CYP450 Enzyme Activity in Human and Rat Liver Microsomes[J]. Asian journal of ecotoxicology, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001

对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用

    作者简介: 史丰收(1998—),女,研究实习员,研究方向为化学品安全,E-mail:1964424654@qq.com
    通讯作者: 陈云霞, E-mail: chenyunxia2009@126.com 苏宁, E-mail: sun@caiq.org.cn
  • 基金项目:

    公益性科研院所基本科研业务费专项资金资助项目(2020JK035)

  • 中图分类号: X171.5

Inhibitory Effects of Propylparaben and Butylparaben on CYP450 Enzyme Activity in Human and Rat Liver Microsomes

    Corresponding authors: Chen Yunxia, chenyunxia2009@126.com ;  Su Ning, sun@caiq.org.cn
  • Fund Project:
  • 摘要: 本文目的是研究对羟基苯甲酸丙酯(羟苯丙酯;propylparaben,PP)和对羟基苯甲酸丁酯(羟苯丁酯;butylparaben,BP)对大鼠肝微粒体(rat liver microsomes,RLM)和人肝微粒体(human liver microsomes,HLM)细胞色素P450酶(cytochrome P450 enzyme,CYP)活性的抑制作用,并评价它们的相互作用潜能。在体外将系列浓度的羟苯丙酯和羟苯丁酯与大鼠和人肝微粒体孵育60 min,以非那西丁、安非他酮、甲苯磺丁脲、氯唑沙宗、香豆素、右美沙芬和咪达唑仑为CYP探针底物,应用质谱定量检测各探针底物的代谢产物生成量,计算得到IC50Ki值,评价2种化学受试物对大鼠和人肝微粒体CYP450酶的抑制活性和抑制类型,并对抑制强度进行分级。大鼠和人肝微粒体中羟苯丙酯是CYP1A2酶的中等强度抑制剂,羟苯丁酯在大鼠肝微粒体中是CYP1A2酶的弱抑制剂,在人肝微粒体中是CYP1A2酶的中等强度抑制剂,观察到对其他CYP450酶无抑制作用,这与用软件预测的羟苯丙酯和羟苯丁酯对CYP450酶的抑制种类结果一致,分子对接的结果也印证了羟苯丙酯和羟苯丁酯对CYP1A2酶活性的抑制作用,按照构效关系和同源CYP的物种敏感度预测模型,本文关于CYP的研究结果可以类推到其他哺乳动物和人类。
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  • 收稿日期:  2021-08-12
史丰收, 赵潺, 王聪, 李雅倩, 余梦圆, 郑君, 李萍, 李贺, 商静静, 顾凌郡, 陈云霞, 苏宁. 对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用[J]. 生态毒理学报, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001
引用本文: 史丰收, 赵潺, 王聪, 李雅倩, 余梦圆, 郑君, 李萍, 李贺, 商静静, 顾凌郡, 陈云霞, 苏宁. 对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用[J]. 生态毒理学报, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001
Shi Fengshou, Zhao Chan, Wang Cong, Li Yaqian, Yu Mengyuan, Zheng Jun, Li Ping, Li He, Shang Jingjing, Gu Lingjun, Chen Yunxia, Su Ning. Inhibitory Effects of Propylparaben and Butylparaben on CYP450 Enzyme Activity in Human and Rat Liver Microsomes[J]. Asian journal of ecotoxicology, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001
Citation: Shi Fengshou, Zhao Chan, Wang Cong, Li Yaqian, Yu Mengyuan, Zheng Jun, Li Ping, Li He, Shang Jingjing, Gu Lingjun, Chen Yunxia, Su Ning. Inhibitory Effects of Propylparaben and Butylparaben on CYP450 Enzyme Activity in Human and Rat Liver Microsomes[J]. Asian journal of ecotoxicology, 2022, 17(4): 87-95. doi: 10.7524/AJE.1673-5897.20210812001

对羟基苯甲酸丙酯和对羟基苯甲酸丁酯对人和大鼠肝微粒体CYP450酶活性的抑制作用

    通讯作者: 陈云霞, E-mail: chenyunxia2009@126.com ;  苏宁, E-mail: sun@caiq.org.cn
    作者简介: 史丰收(1998—),女,研究实习员,研究方向为化学品安全,E-mail:1964424654@qq.com
  • 1. 中国检科院化妆品技术中心, 北京 100176;
  • 2. 中检科(北京)化妆品技术有限公司, 北京 100176;
  • 3. 中国检科院化学品安全研究所, 北京 100176
基金项目:

公益性科研院所基本科研业务费专项资金资助项目(2020JK035)

摘要: 本文目的是研究对羟基苯甲酸丙酯(羟苯丙酯;propylparaben,PP)和对羟基苯甲酸丁酯(羟苯丁酯;butylparaben,BP)对大鼠肝微粒体(rat liver microsomes,RLM)和人肝微粒体(human liver microsomes,HLM)细胞色素P450酶(cytochrome P450 enzyme,CYP)活性的抑制作用,并评价它们的相互作用潜能。在体外将系列浓度的羟苯丙酯和羟苯丁酯与大鼠和人肝微粒体孵育60 min,以非那西丁、安非他酮、甲苯磺丁脲、氯唑沙宗、香豆素、右美沙芬和咪达唑仑为CYP探针底物,应用质谱定量检测各探针底物的代谢产物生成量,计算得到IC50Ki值,评价2种化学受试物对大鼠和人肝微粒体CYP450酶的抑制活性和抑制类型,并对抑制强度进行分级。大鼠和人肝微粒体中羟苯丙酯是CYP1A2酶的中等强度抑制剂,羟苯丁酯在大鼠肝微粒体中是CYP1A2酶的弱抑制剂,在人肝微粒体中是CYP1A2酶的中等强度抑制剂,观察到对其他CYP450酶无抑制作用,这与用软件预测的羟苯丙酯和羟苯丁酯对CYP450酶的抑制种类结果一致,分子对接的结果也印证了羟苯丙酯和羟苯丁酯对CYP1A2酶活性的抑制作用,按照构效关系和同源CYP的物种敏感度预测模型,本文关于CYP的研究结果可以类推到其他哺乳动物和人类。

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