天然植物药肝脏内DNA加合物的研究进展
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摘要
天然药物包括植物药、动物药和海洋药物,在我国天然植物药的使用有悠久的历史。但是随着现代科学技术的发展,马兜铃酸肾病的发现,人们逐渐对天然植物药的安全性产生了怀疑。此后多年,陆续从天然植物药中分离了多种有肝肾毒性的化合物。重点围绕已知的化合物代谢形成DNA加合物的过程阐述天然植物药致突变致癌分子机制的研究进展。
Natural medicines include botanicals,animal medicines and marine medicines.In China,there is a long history of the use of natural botanicals.However,with the development of modern science and technology,the discovery of aristolochic acid nephropathy,people have gradually doubted the safety of natural botanical drugs.Since then,many compounds with liver and kidney toxicity have been isolated from natural botanicals.This paper focuses on the research progress of molecular mechanisms of mutagenic carcinogenesis of natural botanicals by the process of known compound metabolism in the form of DNA adducts.
Natural medicines include botanicals,animal medicines and marine medicines.In China,there is a long history of the use of natural botanicals.However,with the development of modern science and technology,the discovery of aristolochic acid nephropathy,people have gradually doubted the safety of natural botanical drugs.Since then,many compounds with liver and kidney toxicity have been isolated from natural botanicals.This paper focuses on the research progress of molecular mechanisms of mutagenic carcinogenesis of natural botanicals by the process of known compound metabolism in the form of DNA adducts.
引文
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[7]陆华,马康目,孙皎,等.Ames试验与MLA试验检测两味含马兜铃酸中药的致突变性[J].癌变.畸变:突变,2007,19(6):484-486.
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[11]柏兆方,徐广,王伽伯,等.马兜铃酸及其衍生物致癌性研究进展及应对措施[J].药学进展,2018(3):164-169.
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[14]Ishii Y,Okamura T,Inoue T,et al.Chemical structure determination of DNA bases modified by active metabolites of lucidin-3-O-primeveroside[J].Chem Res Toxicol,2010,23(1):134-141.
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[18]Yang Y,Yan J,Doerge D,et al.Metabolic activation of the tumorigenic pyrrolizidine alkaloid,riddelliine,leading to DNA adduct formation in vivo[J].Chem Res Toxicol,2001,14(1):101-109.
[19]周媛.中国人群药物性肝损害的流行病学:系统分析患者21789例[D].上海:第三军医大学,2013.
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[21]Ricicki E M,Soglia J R,Teitel C,et al.Detection and quantification of N-(Deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human pancreas tissue using capillary liquid chromatography-microelectrospray mass spectrometry[J].Chem Res Toxicol,2005,18(4):692-699.
[22]Kao C Y,Giese R W.Measurement of N7-(2'-hydroxyethyl)guanine in human DNA by gas chromatography electron capture mass spectrometry[J].Chem Res Toxicol,2005,18(1):70-75.
[23]刘磊.生物样品自动化在线固相萃取—高效液相色谱分析方法学研究[D].天津:南开大学,2013.
[24]Feng G F,Liu S,Pi Z F,et al.Study on the I phase metabolism of ginsenoside in vitro by ultra performance liquid chromatography coupled with mass spectrometry[J].J Chin Mass Spectr Soc,2017,38(4):450-459.
[25]Zubel T,Bürkle A,Mangerich A.Mass spectrometric analysis of sulfur mustard-induced biomolecular adducts:Are DNA adducts suitable biomarkers of exposure?[J].Toxicol Lett,2017,293:21-30.
[26]Gangl E T,Turesky R J,Vouros P.Determination of in vitro-and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry[J].Chem Res Toxicol,1999,12(10):1019-1027.
[27]Tretyakova N,Matter B,Ogdie A,et al.Locating nucleobase lesions within DNA sequences by MALDITOF mass spectral analysis of exonuclease ladders[J].Chem Res Toxicol,2001,14(8):1058-1070.
[28]Saha M,Abushamaa A,Giese R W.General method for determining ethylene oxide and related N7-guanine DNA adducts by gas chromatography-electron capture mass spectrometry[J].Journal of Chromatography A,1995,712(2):345-354.
[29]Deforce D.Analysis of the DNA adducts of phenyl glycidyl ether in a calf thymus DNA hydrolysate by capillary zone electrophoresis-electrospray mass spectrometry:evidence for phosphate alkylation[J].Carcinogenesis,1998,19(6):1077-1086.
[30]Chan W,Yue H,Poon W T,et al.Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver by using liquid chromatography-electrospray ionization mass spectrometry[J].Mut Res,2008,646(1):17-24.
[31]田禾苗,程雪梅,王长虹,等.HPLC法同时测定马兜铃中4种成分[J].中成药,2016,38(3):560-565.
[32]乌日汗.应用暴露相关的剂量估算模型(ERDEM)为苯并(a)芘构建人体PBPK/PD模型的研究[D].呼和浩特:内蒙古医科大学,2016.
[33]Zhang X,Tsang A M,Okino M S,et al.A physiologically based pharmacokinetic/pharmacodynamic model for carbofuran in sprague-dawley rats using the exposurerelated dose estimating model[J].Toxicol Sci,2007,100(2):345-359.
[34]巢迎妍,张辉,刘艳,等.应用暴露相关的剂量估算模型(ERDEM)构建甲胺磷的大鼠生理药代动力学/药效学(PBPK/PD)模型[J].实用药物与临床,2015,18(2):174-177.
[35]StiborováM,Arlt V M,Schmeiser H H.DNA adducts formed by aristolochic acid are unique biomarkers of exposure and explain the initiation phase of upper urothelial cancer[J].Int J Mol Sci,2017,18(10).pii:E2144.doi:10.3390/ijms18102144.
[36]Michl J,Bello O,Kite G C,et al.Medicinally used asarum species:High-resolution LC-MS Analysis of aristolochic acid analogs and in vitro toxicity screening in HK-2 cells[J].Front Pharmacol,2017,8:215
[2]杨桂蓉,喻凯,陆彩鹏,等.苍术苷的致突变AMES试验研究[J].中华中医药学刊,2013(3):637-638.
[3]孙恩亭,卜新柱,钱怡宁,等.中药雄黄的致突变性实验研究[J].中国中医基础医学杂志,1998(11):52-52.
[4]赵源,吴文斌,汤家铭.雄黄致体内外染色体畸变[J].中国实验方剂学杂志,2012,18(14):245-249.
[5]曹易懿,栾洋,任进.汉防己甲素的遗传毒性评价[J].毒理学杂志,2010(2):172-174.
[6]董伟华,郑智敏,刘桂亭.中药大黄、槐米、红花提取物的致突变作用[J].郑州大学学报(医学版),1991(4):330-333.
[7]陆华,马康目,孙皎,等.Ames试验与MLA试验检测两味含马兜铃酸中药的致突变性[J].癌变.畸变:突变,2007,19(6):484-486.
[8]Vanherweghem J L,Tielemans C,Abramowicz D,et al.Rapidly progressive interstitial renal fibrosis in young women:association with slimming regimen including Chinese herbs[J].Lancet,1993,341(8842):387-391.
[9]孙阳.中药马兜铃酸肾病与巴尔干肾病[J].国际泌尿系统杂志,1995(2):58-59.
[10]李瑛,曾彩虹.马兜铃酸肾毒性作用及其机制研究[J].肾脏病与透析肾移植杂志,2003,12(6):558-563.
[11]柏兆方,徐广,王伽伯,等.马兜铃酸及其衍生物致癌性研究进展及应对措施[J].药学进展,2018(3):164-169.
[12]宋海波,任经天,杨乐,等.马兜铃酸毒性研究进展及风险因素分析[J].中国中药杂志,2014,39(12):2246-2250.
[13]Wang Y P,Jian Y,Beger R D,et al.Metabolic activation of the tumorigenic pyrrolizidine alkaloid,monocrotaline,leading to DNA adduct formation in vivo[J].Cancer Lett,2005,2(1):74-79.
[14]Ishii Y,Okamura T,Inoue T,et al.Chemical structure determination of DNA bases modified by active metabolites of lucidin-3-O-primeveroside[J].Chem Res Toxicol,2010,23(1):134-141.
[15]陈进军,于增杰,林红英,等.千里光提取物的小鼠骨髓微核试验[J].中兽医医药杂志,2007,26(1):20-22.
[16]司南,王宏洁,杨健,等.茜草中Lucidin,Lucidin-3-Oprimeveroside及大叶茜草素在小鼠血浆中代谢趋势的初步研究[J].中国实验方剂学杂志,2010,16(2):113-115.
[17]王增涛.紫茜抗癌胶囊指纹图谱及稳定性、毒性的研究[D].延吉:延边大学,2009.
[18]Yang Y,Yan J,Doerge D,et al.Metabolic activation of the tumorigenic pyrrolizidine alkaloid,riddelliine,leading to DNA adduct formation in vivo[J].Chem Res Toxicol,2001,14(1):101-109.
[19]周媛.中国人群药物性肝损害的流行病学:系统分析患者21789例[D].上海:第三军医大学,2013.
[20]Zhang L K,Ren Y,Rempel D,et al.Determination of photomodified oligodeoxynucleotides by exonuclease digestion,matrix-assisted laser desorption/ionization and post-source decay mass spectrometry[J].J Am Soc Mass Spectr,2001,12(10):1127-1135.
[21]Ricicki E M,Soglia J R,Teitel C,et al.Detection and quantification of N-(Deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human pancreas tissue using capillary liquid chromatography-microelectrospray mass spectrometry[J].Chem Res Toxicol,2005,18(4):692-699.
[22]Kao C Y,Giese R W.Measurement of N7-(2'-hydroxyethyl)guanine in human DNA by gas chromatography electron capture mass spectrometry[J].Chem Res Toxicol,2005,18(1):70-75.
[23]刘磊.生物样品自动化在线固相萃取—高效液相色谱分析方法学研究[D].天津:南开大学,2013.
[24]Feng G F,Liu S,Pi Z F,et al.Study on the I phase metabolism of ginsenoside in vitro by ultra performance liquid chromatography coupled with mass spectrometry[J].J Chin Mass Spectr Soc,2017,38(4):450-459.
[25]Zubel T,Bürkle A,Mangerich A.Mass spectrometric analysis of sulfur mustard-induced biomolecular adducts:Are DNA adducts suitable biomarkers of exposure?[J].Toxicol Lett,2017,293:21-30.
[26]Gangl E T,Turesky R J,Vouros P.Determination of in vitro-and in vivo-formed DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline by capillary liquid chromatography/microelectrospray mass spectrometry[J].Chem Res Toxicol,1999,12(10):1019-1027.
[27]Tretyakova N,Matter B,Ogdie A,et al.Locating nucleobase lesions within DNA sequences by MALDITOF mass spectral analysis of exonuclease ladders[J].Chem Res Toxicol,2001,14(8):1058-1070.
[28]Saha M,Abushamaa A,Giese R W.General method for determining ethylene oxide and related N7-guanine DNA adducts by gas chromatography-electron capture mass spectrometry[J].Journal of Chromatography A,1995,712(2):345-354.
[29]Deforce D.Analysis of the DNA adducts of phenyl glycidyl ether in a calf thymus DNA hydrolysate by capillary zone electrophoresis-electrospray mass spectrometry:evidence for phosphate alkylation[J].Carcinogenesis,1998,19(6):1077-1086.
[30]Chan W,Yue H,Poon W T,et al.Quantification of aristolochic acid-derived DNA adducts in rat kidney and liver by using liquid chromatography-electrospray ionization mass spectrometry[J].Mut Res,2008,646(1):17-24.
[31]田禾苗,程雪梅,王长虹,等.HPLC法同时测定马兜铃中4种成分[J].中成药,2016,38(3):560-565.
[32]乌日汗.应用暴露相关的剂量估算模型(ERDEM)为苯并(a)芘构建人体PBPK/PD模型的研究[D].呼和浩特:内蒙古医科大学,2016.
[33]Zhang X,Tsang A M,Okino M S,et al.A physiologically based pharmacokinetic/pharmacodynamic model for carbofuran in sprague-dawley rats using the exposurerelated dose estimating model[J].Toxicol Sci,2007,100(2):345-359.
[34]巢迎妍,张辉,刘艳,等.应用暴露相关的剂量估算模型(ERDEM)构建甲胺磷的大鼠生理药代动力学/药效学(PBPK/PD)模型[J].实用药物与临床,2015,18(2):174-177.
[35]StiborováM,Arlt V M,Schmeiser H H.DNA adducts formed by aristolochic acid are unique biomarkers of exposure and explain the initiation phase of upper urothelial cancer[J].Int J Mol Sci,2017,18(10).pii:E2144.doi:10.3390/ijms18102144.
[36]Michl J,Bello O,Kite G C,et al.Medicinally used asarum species:High-resolution LC-MS Analysis of aristolochic acid analogs and in vitro toxicity screening in HK-2 cells[J].Front Pharmacol,2017,8:215