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人肝CYP3A参与了山冈橐吾碱的代谢及其肝毒性代谢物的形成(英文) 被引量:5
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作者 柳晓泉 林鸽 +1 位作者 王广基 钱之玉 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2002年第1期15-20,共6页
目的 在体外研究山冈橐吾碱在人肝微粒体内的代谢及参与其代谢的主要的CYP4 5 0酶 ,探讨其代谢致毒机理。方法 采用人肝微粒体研究山冈橐吾碱的主要代谢方式和代谢物。在体外运用CYP4 5 0酶的选择性抑制剂和cDNA表达的人肝CYP4 5 0酶 ... 目的 在体外研究山冈橐吾碱在人肝微粒体内的代谢及参与其代谢的主要的CYP4 5 0酶 ,探讨其代谢致毒机理。方法 采用人肝微粒体研究山冈橐吾碱的主要代谢方式和代谢物。在体外运用CYP4 5 0酶的选择性抑制剂和cDNA表达的人肝CYP4 5 0酶 ,探讨其对山冈橐吾碱的代谢及肝毒性的吡咯代谢物形成的影响及参与山冈橐吾碱代谢的主要的CYP4 5 0酶。结果 山冈橐吾碱在人肝微粒体内的主要代谢物为肝毒性的吡咯代谢物 :去氢倒千里光裂碱 ,7 谷胱甘肽基 去氢倒千里光裂碱 ,7,9 二谷胱甘肽基去氢倒千里光裂碱和山冈囊吾酸。CYP4 5 0特异性抑制剂α 萘黄酮 (抑制CYP1A2 )、黄胺苯吡唑 (抑制CYP2C)、奎尼丁 (抑制CYP2D6 )和二乙基二硫代氨基甲酸钠 (抑制CYP2E1)对山冈橐吾碱的代谢无明显的影响。但CYP3A的特异性抑制剂酮康唑和三乙酰竹桃霉素可以显著地抑制山冈橐吾碱的代谢及其吡咯代谢物和结合型吡咯物的形成。此外 ,在cDNA表达的人肝CYP3A4的温孵液中 ,山冈橐吾碱被代谢成相应的吡咯代谢物 ,而山冈橐吾碱在cDNA表达的人肝CYP1A2、CYP2C9、CYP2D6和CYP2E1温孵液中无代谢。结论 山冈橐吾碱在人肝微粒体内的主要代谢方式是形成肝毒性吡咯代谢物 ,CYP3A作为主要的CYP4 5 0酶参与了山冈橐吾碱的代谢及其肝毒性吡咯代谢? 展开更多
关键词 山冈橐吾碱 肝脏 微粒体 转化 毒性代谢物 CYP3A4
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谷胱甘肽的解毒作用与毒性代谢物 被引量:58
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作者 程元恺 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 1994年第5期395-399,共5页
谷胱甘肽是细胞内重要的含SH基的非蛋白分子,它对氧自由基、有机氢过氧化物以及亲电子剂的灭活起着极重要的作用。但近年来的研究表明,一些连位二卤烷烃、卤烯烃、含酮结构的化合物以及一些异氰酸酯、异硫氰酸酯、醛、α,β-不饱... 谷胱甘肽是细胞内重要的含SH基的非蛋白分子,它对氧自由基、有机氢过氧化物以及亲电子剂的灭活起着极重要的作用。但近年来的研究表明,一些连位二卤烷烃、卤烯烃、含酮结构的化合物以及一些异氰酸酯、异硫氰酸酯、醛、α,β-不饱和醛等与谷胱甘肽轭合后可导致毒性代谢物的形成。 展开更多
关键词 谷胱甘肽 解毒作用 毒性代谢物
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肥胖者药物动力学变化 被引量:2
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作者 杨惠娣 施安国 安富荣 《中国临床药学杂志》 CAS 1999年第S1期79-81,共3页
体内脂肪过多的积聚会使高血压、动脉硬化、冠心、糖尿病发病率增加,也使乳腺癌、结肠癌、前列腺癌、子宫内腺癌、卵巢癌等的发病率增加,因而一般来说肥胖者比非肥胖者更需要医学治疗,值得重视的是治疗药物的药物动力学与药效学在肥胖... 体内脂肪过多的积聚会使高血压、动脉硬化、冠心、糖尿病发病率增加,也使乳腺癌、结肠癌、前列腺癌、子宫内腺癌、卵巢癌等的发病率增加,因而一般来说肥胖者比非肥胖者更需要医学治疗,值得重视的是治疗药物的药物动力学与药效学在肥胖者和非肥胖者可能有所改变,例如药物的分布容积(Vd)和清除率(CL)的变比会影响到药物的作用,所以需明确肥胖者药物动力学性质的变化. 展开更多
关键词 动力学 肥胖者 表观分布容积 利用度 白脂肪组织 血浆蛋白结合 细胞色素P450 普鲁卡因 毒性代谢物 肾小球过滤
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还原型谷胱甘肽治疗酒精性脂肪肝46例观察 被引量:2
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作者 刘三都 杨庆坤 《实用中医药杂志》 2004年第9期540-540,共1页
关键词 还原型谷胱甘肽 酒精性脂肪肝 血脂 毒性代谢物 胆酸代谢
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Manila clam Venerupis philippinarum as a biomonitor to metal pollution 被引量:3
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作者 吴惠丰 吉成龙 +3 位作者 王清 刘小莉 赵建民 冯江华 《Chinese Journal of Oceanology and Limnology》 SCIE CAS CSCD 2013年第1期65-74,共10页
The Manila clam Venerupis philippinarum is a good biomonitor/bioindicator to marine metal pollution and is frequently used in aquatic toxicology. Two dominant pedigrees (white and zebra) of clam are distributed in the... The Manila clam Venerupis philippinarum is a good biomonitor/bioindicator to marine metal pollution and is frequently used in aquatic toxicology. Two dominant pedigrees (white and zebra) of clam are distributed in the Bohai Sea; however, little attention has been paid to potential biological differences between these two pedigrees. In this study, we tested the sensitivity of both pedigrees to marine metal (cadmium and zinc) pollution biomonitoring and marine environmental toxicology. Results demonstrate significant biological differences in gills of white and zebra clams based on metabolic profiles and antioxidant enzyme activities. In addition, we found that hypotaurine, malonate and homarine were relatively high in white clam gills, while alanine, arginine, glutamate, succinate, 4-aminobutyrate, taurine and betaine were high in zebra clam gills. Zebra clam gills were also more sensitive to a mixture of Cd and Zn, as shown by antioxidant enzyme activities and metabolic profiles, but white clam gills could accumulate more Zn. Therefore, we suggest that the white pedigree can be used as a biomonitor to marine Zn pollution, whereas the zebra pedigree can be used for toxicology studies on Cd and Zn mixed pollution. 展开更多
关键词 Manila clam Venerupisphilippinarum BIOMONITOR BIOMARKER metabolomics
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Effect of Ganduqing Granule on metabolic disorder and liver dysfunction in patients with chronic hepatitis B
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作者 You-Ping Liu Bo Li +3 位作者 Xiao-Dong Wang Shao-Ping Mi En-Ze Liu Mei Wei 《Traditional Medicine Research》 2017年第4期161-168,共8页
Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 p... Objective:This study investigated the potential mechanisms of Ganduqing Granule(GDQG)in improving the liver function in patients with chronic hepatitis B(CHB).Methods:Plasma samples from 30 healthy volunteers and 30 patients with CHB before and after the treatment with GDQG were measured for the alterations in liver function and metabolites,using the method of ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry.Results:Patients with CHB developed severe liver dysfunction,which was associated with the higher plasma levels of 8 metabolites when compared with those of the normal control(P<0.05).Interestingly,after treatment with GDQG for 3 weeks,the 8 metabolites were significantly reduced(P<0.05).Among them,glycochenodeoxycholate-3-sulfate,glycochenodeoxycholic acid-3-glucuronide,taurochenodeoxycholic acid,and 7b-hydroxy-3-oxo-5b-cholanoic acid were associated with the metabolism of bile acids,while 3b,16a-dihydroxyandrostenone sulfate,lysophosphatidylcholine(C18:3),and lysophosphatidylethanolamine(C22:1)were related to the metabolism of lipids.2,6-Diamino-4-hydroxy-5-N-methylformamidopyrimidine was related to hepatic oxidative stress.Meanwhile,liver damage in patients was greatly reduced.Conclusion:Treatment with GDQG has improved liver function of patients with CHB through the possible mechanism of adjusting the metabolic disorders related to lipids,bile acids,and oxidative stress. 展开更多
关键词 Ganduqing Granule Chronic hepatitis B PLASMA METABOLITES
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Application of LC-MS based glutathione-trapped reactive metabolites in the discovery of toxicity of traditional Chinese medicine
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作者 Xiao-Mei Liu Hong Lv +3 位作者 Xiao-Ming Wang Ya-Qing Guo Ting-Ting Li Gui-Xiang Pan 《TMR Modern Herbal Medicine》 2018年第4期209-219,共11页
We summarized the discovery of liquid chromatography mass spectrometry (LC-MS) based glutathione (GSH) capture of reactive metabolites in traditional Chinese medicine (TCM), which provides scientific basis for ... We summarized the discovery of liquid chromatography mass spectrometry (LC-MS) based glutathione (GSH) capture of reactive metabolites in traditional Chinese medicine (TCM), which provides scientific basis for further research and clinical application of Chinese medicine toxicity discovery. This dissertation overviews relevant literatures of GSH capture of reactive metabolites in recent years. And then we review the principles and methods of LC-MS based GSH capture of reactive metabolites, as well as the research progress in the discovery of toxicity of TCM including pyrrolizidine alkaloids, furans and quinoid species. The review shows that the representative compounds of TCM includes adonifoline, lasiocarpine, diosbulbin B and safrol are well dctected by LC-MS based GSH capture technique. And the main analytic systems of LC-MS are triple quadrupole and Q-Trap mass spectrometer. Constant neutral loss scan (CNLS), precursor ion scan (PIS) and multiple reaction monitor (MRM) are main detection methods to monitor the characteristic GSH conjugate fragmentations. The approach of LC-MS based GSH-trapped metabolites has a good application prospect in the discovery of toxic components of TCM. 展开更多
关键词 glutathione conjugation Liquid Chromatography Mass Spectrometry Reactive metabolites TOXICITY traditional Chinese medicine
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