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含雄黄的牛黄解毒片与砷剂在细胞培养和小鼠体内的毒理学评价比较

Toxicology evaluation of realgar-containing niu-huang-jie-du pian as compared to arsenicals in cell cultures and in mice.

作者信息

Miao Jia-Wei, Liang Shi-Xia, Wu Qin, Liu Jie, Sun An-Sheng

机构信息

Key Lab of Basic Pharmacology, Zunyi Medical College, Zunyi 563000, China ; Chongqing Three Gorges Medical College, Chongqing 404120, China.

出版信息

ISRN Toxicol. 2011 Oct 13;2011:250387. doi: 10.5402/2011/250387. Print 2011.

DOI:10.5402/2011/250387
PMID:23724280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3658795/
Abstract

Niu-Huang-Jie-Du Pian (NHJD) is a widely used traditional Chinese medicine containing realgar (As4S4). Realgar has been included in many traditional medicines, but is often taken as arsenite for risk assessment. To evaluate true risk of realgar and realgar-containing NHJD, their toxicity was compared with common arsenicals. In cultured cells, the LC50 for NHJD (1200 μM) and realgar (2000 μM) was much higher than arsenite(35 μM), arsenic trioxide (280 μM), and arsenate (400 μM). Acute toxicity in mice showed more severe liver and kidney injury after arsenite or arsenate, but was mild after realgar and NHJD, corresponding to cellular and tissue arsenic accumulation. The expressions of arsenic-sensitive stress gene metallothionein-1 were increased 3-7-folds after arsenite or arsenate, but were unaltered after NHJD and realgar. Thus, realgar and NHJD are much less toxic than arsenite and arsenate. The use of total arsenic to evaluate the safety of realgar and realgar-containing NHJD is inappropriate.

摘要

牛黄解毒片(NHJD)是一种广泛使用的含有雄黄(As4S4)的传统中药。雄黄已被纳入许多传统药物中,但在风险评估时通常被视为亚砷酸盐。为了评估雄黄及含雄黄的牛黄解毒片的真实风险,将它们的毒性与常见砷化合物进行了比较。在培养细胞中,牛黄解毒片(1200μM)和雄黄(2000μM)的半数致死浓度远高于亚砷酸盐(35μM)、三氧化二砷(280μM)和砷酸盐(400μM)。小鼠急性毒性实验表明,亚砷酸盐或砷酸盐处理后肝脏和肾脏损伤更严重,而雄黄和牛黄解毒片处理后则较轻,这与细胞和组织中的砷积累情况相符。亚砷酸盐或砷酸盐处理后,砷敏感应激基因金属硫蛋白-1的表达增加了3至7倍,但牛黄解毒片和雄黄处理后未发生改变。因此,雄黄和牛黄解毒片的毒性远低于亚砷酸盐和砷酸盐。用总砷来评估雄黄及含雄黄的牛黄解毒片的安全性是不合适的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/6ea55c9b4ef1/ISRN.TOXICOLOGY2011-250387.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/4e6c54496809/ISRN.TOXICOLOGY2011-250387.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/fde54e118a94/ISRN.TOXICOLOGY2011-250387.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/3f00c56f8b7a/ISRN.TOXICOLOGY2011-250387.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/6ea55c9b4ef1/ISRN.TOXICOLOGY2011-250387.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/4e6c54496809/ISRN.TOXICOLOGY2011-250387.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/fde54e118a94/ISRN.TOXICOLOGY2011-250387.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/3f00c56f8b7a/ISRN.TOXICOLOGY2011-250387.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad4/3658795/6ea55c9b4ef1/ISRN.TOXICOLOGY2011-250387.004.jpg

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本文引用的文献

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The medicinal use of realgar (As₄S₄) and its recent development as an anticancer agent.雄黄(As₄S₄)的药用及其作为抗癌药物的最新研究进展。
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Realgar, cinnabar and An-Gong-Niu-Huang Wan are much less chronically nephrotoxic than common arsenicals and mercurials.
二硫化砷通过诱导细胞凋亡、阻滞细胞周期和抑制促生存信号对人乳腺癌细胞的抗癌疗效。
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