左甜甜, 所雅琼, 罗飞亚, 孔德娟, 金红宇, 孙磊, 邢书霞, 郭愿生, 王钢力, 马双成. 基于体外消化/Caco-2细胞模型分析乌药水煎液中铅、镉和砷的生物可给量及累积风险评估J. 药学学报, 2023, 58(8): 2461-2467. DOI: 10.16438/j.0513-4870.2022-0888
引用本文: 左甜甜, 所雅琼, 罗飞亚, 孔德娟, 金红宇, 孙磊, 邢书霞, 郭愿生, 王钢力, 马双成. 基于体外消化/Caco-2细胞模型分析乌药水煎液中铅、镉和砷的生物可给量及累积风险评估J. 药学学报, 2023, 58(8): 2461-2467. DOI: 10.16438/j.0513-4870.2022-0888
ZUO Tian-tian, SUO Ya-qiong, LUO Fei-ya, KONG De-juan, JIN Hong-yu, SUN Lei, XING Shu-xia, GUO Yuan-sheng, WANG Gang-li, MA Shuang-cheng. Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessmentJ. Acta Pharmaceutica Sinica, 2023, 58(8): 2461-2467. DOI: 10.16438/j.0513-4870.2022-0888
Citation: ZUO Tian-tian, SUO Ya-qiong, LUO Fei-ya, KONG De-juan, JIN Hong-yu, SUN Lei, XING Shu-xia, GUO Yuan-sheng, WANG Gang-li, MA Shuang-cheng. Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessmentJ. Acta Pharmaceutica Sinica, 2023, 58(8): 2461-2467. DOI: 10.16438/j.0513-4870.2022-0888

基于体外消化/Caco-2细胞模型分析乌药水煎液中铅、镉和砷的生物可给量及累积风险评估

Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessment

  • 摘要: 为了考察乌药水煎液中铅(Pb)、镉(Cd) 和砷(As) 的生物可给量, 并对其风险进行评估, 本研究采用电感耦合等离子体质谱(ICP-MS) 法测定乌药中Pb、Cd和As的残留量; 建立体外模拟消化/Caco-2细胞模型考察乌药水煎液中Pb、Cd和As的生物可给量; 采用靶器官毒性剂量(TTD) 法对于乌药中Pb、Cd和As的残留总量以及水煎液中生物可给量联合暴露产生的累积风险进行评估。结果表明: 乌药中Pb、Cd和As的残留总量分别为2.901~3.872、1.299~1.800和0.062~0.216 mg·kg-1。经Caco-2细胞转运后, 乌药水煎液中Pb、Cd、As的生物可给浓度分别为0.045~0.080、0.070~0.112和0.004~0.018 mg·kg-1。风险评估结果表明: 以乌药中重金属残留总量计算, 对于作用终点神经系统, 三样品中重金属联合暴露产生的累积风险较高。然而, 煎煮并经过Caco-2细胞转运后, 对于作用终点心血管、血液、神经系统、肾脏、睾丸, 所有批次乌药中TTD法修正的危害指数(hazard index, HI) 值< 1, 健康风险可接受。该项目研究将为准确评价中药中重金属及有害元素的健康风险、建立更科学的重金属及有害元素限量标准奠定理论和技术基础。

     

    Abstract: Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

     

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