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基于形态和价态的雄黄中砷形态吸收研究

Study on the Absorption of Arsenic Species in Realgar Based on the Form and Valence.

作者信息

Sun Mingyi, Li Yaolei, Wang Ying, Wu Huimin, Liu Jing, You Longtai, Peng HuLinyue, Huang Huating, Jin Hongyu, Dong Xiaoxu, Qu Changhai, Yin Xingbin, Ni Jian

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, National Institutes for Food and Drug Control, Beijing 102629, China.

出版信息

Evid Based Complement Alternat Med. 2022 Aug 23;2022:1026672. doi: 10.1155/2022/1026672. eCollection 2022.

Abstract

At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an dissolution study, an unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10, 6.1 × 10 and 5.8 × 10 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The and AUC of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L/343.977 ng h mL, 21.626 ng L/47.310 ng h mL, and 2.372 ng L/30.429 ng h mL, respectively. and MRT of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.

摘要

目前,已开展多项实验研究雄黄及其方剂中总砷含量的变化,但其形态及价态的研究较少。我们通过溶出度研究、单向肠道灌流研究、Caco-2细胞跨膜转运以及大鼠药代动力学研究,从吸收角度评估了雄黄中砷形态浓度的变化。在胃肠道中,砷形态主要以无机形式的AsIII和AsV存在。可溶性砷在4小时人工胃液和8小时人工肠液中的累积溶出率分别为21.99%和59.20%。雄黄中可溶性砷在大鼠十二指肠、空肠和回肠的表观渗透系数分别为5.4×10、6.1×10和5.8×10 cm/min。在小肠灌流过程中,雄黄中的AsIII在十二指肠和空肠部分转化为AsV。随着转运时间增加,雄黄中可溶性砷在Caco-2细胞中的跨膜转运速率和表观渗透系数升高,这也表明砷形态可能通过被动转运穿过Caco-2细胞单层。雄黄血浆中AsIII、AsV和DMA的Cmax和AUC分别为41.26 ng/L/343.977 ng·h/mL、21.626 ng/L/47.310 ng·h/mL和2.372 ng/L/30.429 ng·h/mL。AsIII、AsV和DMA的Tmax和MRT分别为2.571 h/9.649 h、0.393 h/2.790 h和3.143 h/23.145 h。希望为阐明雄黄中的砷形态提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76b9/9427252/df84b4936eaf/ECAM2022-1026672.001.jpg

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