雄黄的安全性评价和配伍减毒研究
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摘要
雄黄是经典中成药的常见组成药物,因含有硫化砷类成分,其安全性备受关注。介绍了近年国内外对砷存在形式、毒性分子机制基础上,结合含雄黄制剂的临床不良反应报道,探讨了雄黄慢性暴露对实验动物的安全性和减毒研究。并以经典名方六神丸为例,表明方剂配伍对雄黄的减毒效果。提示雄黄制剂在临床合理剂量、用药时间和组方配伍情况下,存在一定安全性。
Realgar is a common component of classical Chinese medicine preparation,which has attracted much attention due to high content of arsenic sulfide.This reviewed the research on the species,toxicity and molecular mechanism of arsenic in recent years.The clinical adverse effects of realgar-containing preparations and the safety of realgar on chronic exposure to experimental animals were analyzed.In particular,the classic Chinese medicine Liushen Wan compatibility reduced realgar-induced toxicity.That illustrated that the Chinese medicine preparations containing realgar clinically used at low dose and reasonable medication time,have certain drug safety.
Realgar is a common component of classical Chinese medicine preparation,which has attracted much attention due to high content of arsenic sulfide.This reviewed the research on the species,toxicity and molecular mechanism of arsenic in recent years.The clinical adverse effects of realgar-containing preparations and the safety of realgar on chronic exposure to experimental animals were analyzed.In particular,the classic Chinese medicine Liushen Wan compatibility reduced realgar-induced toxicity.That illustrated that the Chinese medicine preparations containing realgar clinically used at low dose and reasonable medication time,have certain drug safety.
引文
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[26]周超凡,林育华.传统中药雄黄应用概况及其安全性[J].药物不良反应杂志,2008,10(3):184-189.
[27]陈丽娜,吴丽兰.67例牛黄解毒丸(片)不良反应分析[J].中国中药杂志,2002,27(4):315.
[28]贾小靖.六神丸治疗带状疱疹22例疗效分析[J].临床医药实践,2013,22(5):391-392.
[29]张庆丽,吴倩,谢媛媛,等.六神丸和雄黄中砷的组织分布研究[J].药学学报,2011,46(6):701-706.
[30]张庆丽,吴倩,谢媛媛,等.六神丸和雄黄中砷的毒代动力学研究[J].毒理学杂志,2011,25(5):332-335.
[2]SHEN S,LI XF,CULLEN WR,et al.Arsenic binding to proteins[J].Chem Rev,2013,113(10):7769-7792.
[3]GENG W,KOMINE R,OHTA T,et al.Arsenic speciation in marine product samples:comparison of extraction-HPLC method and digestion-cryogenic trap method[J].Talanta,2009,79(2):369-375.
[4]MA R,SHEN J,WU J,et al.Impact of agronomic practices on arsenic accumulation and speciation in rice grain[J].Environ Pollut,2014,194:217-223.
[5]ZHAO FJ,STROUD JL,EAGLING T,et al.Accumulation,distribution,and speciation of arsenic in wheat grain[J].Environ Sci Technol,2010,44(14):5464-5468.
[6]NEARING MM,KOCH I,REIMER KJ.Arsenic speciation in edible mushrooms[J].Environ Sci Technol,2014,48(24):14203-14210.
[7]ZHOU J,MA H,WU Y,et al.Lipidomic profiling of subchronic As4S4 exposure identifies inflammatory mediators as sensitive biomarkers in rats[J].Metallomics,2018,DOI:10.1039/C8MT00181B.
[8]吴倩.砷元素分析方法研究及其在六神丸安全性再评价中的应用[D].北京:清华大学,2007.
[9]LIU J,LU Y,WU Q,et al.Mineral arsenicals in traditional medicines:orpiment,realgar,and arsenolite[J].J Pharmacol Exp Ther,2008,326(2):363-368.
[10]RODRIGUEZ VM,DEL R L,LIMON-PACHECO JH,et al.Glutathione reductase inhibition and methylated arsenic distribution in Cd1mice brain and liver[J].Toxicol Sci,2005,84(1):157-166.
[11]NARANMANDURA H,IBATA K,SUZUKI KT.Toxicity of dimethylmonothioarsinic acid toward human epidermoid carcinoma A431cells[J].Chem Res Toxicol,2007,20(8):1120-1125.
[12]BACH SJ.Biological methylation[J].Biol Rev Camb Philos Soc.1945,20:158-176.
[13]SUZUKI KT,KATAGIRI A,SAKUMA Y,et al.Distributions and chemical forms of arsenic after intravenous administration of dimethylarsinic and monomethylarsonic acids to rats[J].Toxicol Appl Pharmacol,2004,198(3):336-344.
[14]YAMANAKA K,MIZOI M,TACHIKAWA M,et al.Oxidative DNA damage following exposure to dimethylarsinous iodide:the formation of cis-thymine glycol[J].Toxicol Lett,2003,143(2):145-153.
[15]SUZUKI KT,TOMITA T,OGRA Y,et al.Glutathione-conjugated arsenics in the potential hepato-enteric circulation in rats[J].Chem Res Toxicol,2001,14(12):1604-1611.
[16]HAYAKAWA T,KOBYASHI Y,CUI X,et al.A new metabolic pathway of arsenite:arsenic-glutathione complexes are substrates for human arsenic methyltransferase Cyt19[J].Arch Toxicol,2005,79(4):183-191.
[17]TEMPLETON D,ARIESE F,CORNELIS R,et al.Guidelines for terms related to chemical speciation and fractionation of elements.Definitions,structural aspects,and methodological approaches(IUPAC Recommendations 2000)[J].Pure Appl Chem,2000,72(8):1453-1470.
[18]HUGHES MF.Arsenic toxicity and potential mechanisms of action[J].Toxicol Lett,2002,133(1):1-16.
[19]安艳,李春春,邓晗依.砷诱发氧化应激研究现状[J].国外医学(医学地理分册),2015,36(03):165-173.
[20]GOMEZ SE,DEL RAZO LM,MUNOZ SANCHEZ JL.Induction of DNA damage by free radicals generated either by organic or inorganic arsenic(AsⅢ,MMAⅢand DMAⅢ)in cultures of B and T lymphocytes.[J].Biologic Trace Element Res,2005,108(1):115-126.
[21]陆远富,时京珍,石京山,等.科学评价含雄黄、朱砂中成药的安全性[J].中国中药杂志,2011,36(24):3402-3405.
[22]XIE T,ZHOU X,WANG S,et al.Development and application of a comprehensive lipidomic analysis to investigate Tripterygium wilfordii-induced liver injury[J].Anal Bioanal Chem,2016,408(16):4341-4355.
[23]TAM VC,QUEHENBERGER O,OSHANSKY CM,et al.Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation[J].Cell,2013,154(1):213-227.
[24]O'CONNELL TM,WATKINS PB.The application of metabonomics to predict drug-induced liver injury[J].Clin Pharmacol Ther,2010,88(3):394-399.
[25]王佳佳.六神丸组方配伍对大鼠肝脏重金属砷水平和炎症磷脂的影响[D].南京:南京中医药大学,2017.
[26]周超凡,林育华.传统中药雄黄应用概况及其安全性[J].药物不良反应杂志,2008,10(3):184-189.
[27]陈丽娜,吴丽兰.67例牛黄解毒丸(片)不良反应分析[J].中国中药杂志,2002,27(4):315.
[28]贾小靖.六神丸治疗带状疱疹22例疗效分析[J].临床医药实践,2013,22(5):391-392.
[29]张庆丽,吴倩,谢媛媛,等.六神丸和雄黄中砷的组织分布研究[J].药学学报,2011,46(6):701-706.
[30]张庆丽,吴倩,谢媛媛,等.六神丸和雄黄中砷的毒代动力学研究[J].毒理学杂志,2011,25(5):332-335.