全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用：99美元
投递稿件

查看量下载量

相关文章

更多...

马兜铃酸类物质与肝癌关系的研究进展
The Relationship between Aristolochic Acids and Hepatocellular Carcinoma

DOI: 10.12677/ACM.2020.109293, PP. 1951-1959

Keywords: 马兜铃酸，肝细胞性肝癌，毒理作用
Aristolochic Acid, Hepatocellular Carcinoma, Toxicological Effect

Full-Text   Cite this paper   Add to My Lib

Abstract:

马兜铃酸类物质(aristolochic acids, AAs)是一类普遍存在于马兜铃属和细辛属植物中的硝基菲类有机酸化合物，因具有抗感染、抗癌、增强免疫、调节血压及终止妊娠等作用而广泛应用于中医治疗。但也有研究表明，长期服用含AAs的药物可导致多种系统疾病，如输尿管移行上皮细胞癌、结肠腺癌、乳腺癌浸润性导管癌等，关于AAs诱发各类疾病的机制研究已广泛展开。目前报道AAs暴露对肝脏毒性作用的实验研究尚较少，本文总结了AAs的化学结构和毒理作用机制，并阐述了其诱发肝细胞性肝癌(Hepatocellular carcinoma, HCC)的可能机制，期望为临床合理应用含AAs的药物提供参考。
Aristolochic acid compound (aristolochic acids, AAs) is a kind of nitrophenanthrene organic acid compound commonly found in Aristolochia and Asarum plants. It is widely used in traditional Chinese medicine treatment for anti-infection, anti-cancer, enhanced immunity, regulation of blood pressure and termination of pregnancy. However, some studies showed that long-term use of the drugs containing AAs leads to a variety of diseases, such as transitional cell carcinoma of ureter, colonnade carcinoma, as well as invasive ductal carcinoma of breast. The mechanism of diseases induced by AAs has been widely explored. At present, the experimental study about the toxic effect of AAs on liver is few. This review summarized the chemical structure and toxicological mechanism of AAs, and also analyzed the possible mechanism of (Hepatocellular carcinoma, HCC) induced by AAs, in order to provide reference for the rational use of drugs containing AAs.

References

[1]  Xi, L., Li, X.Q., Guo, H.R., et al. (2020) Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents. World Journal of Traditional Chinese Medicine, 6, 12-25.
https://doi.org/10.4103/wjtcm.wjtcm_33_19
[2]  Abdullah, R., Diaz, L.N., Wesseling, S., et al. (2017) Risk Assessment of Plant Food Supplements and Other Herbal Products Containing Aristolochic Acids Using the Margin of Exposure (MOE) Approach. Food Additives and Contaminants—Part A Chemistry, Analysis, Control, Exposure and Risk Assessment, 34, 135-144.
[3]  Chen, J.S., Lu, C.L., Huang, L.C., et al. (2016) Chronic Kidney Disease Is Associated with Upper Tract Urothelial Carcinoma—A Nationwide Population-Based Cohort Study in Taiwan. Urological Science, 27, S4.
https://doi.org/10.1016/j.urols.2016.05.065
[4]  Hoang, M.L., Chen, C.H., Chen, P.C., et al. (2016) Aristolochic Acid in the Etiology of Renal Cell Carcinoma. Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology, 25, 1600-1608.
https://doi.org/10.1158/1055-9965.EPI-16-0219
[5]  Gold, L.S. and Slone, T.H. (2003) Aristolochic Acid, an Herbal Carcinogen, Sold on the Web after FDA Alert. The New England Journal of Medicine, 349, 1576-1577.
https://doi.org/10.1056/NEJM200310163491619
[6]  Yang, J.D., Hainaut, P., Gores, G.J., et al. (2019) A Global View of Hepatocellular Carcinoma: Trends, Risk, Prevention and Management. Nature Reviews Gastroenterology & Hepatology, 16, 589-604.
https://doi.org/10.1038/s41575-019-0186-y
[7]  路兆宁, 韩泽广. 马兜铃酸相关肝癌发现和验证[J]. 生命的化学, 2019, 39(5): 1045-1048.
[8]  Ng, A.W.T., Poon, S.L., Huang, M.N., et al. (2017) Aristolochic Acids and Their Derivatives Are Widely Implicated in Liver Cancers in Taiwan and throughout Asia. Science Translational Medicine, 9, eaan6446.
https://doi.org/10.1126/scitranslmed.aan6446
[9]  Arlt, V.M., Stiborova, M. and Schmeiser, H.H. (2002) Aristolochic Acid as a Probable Human Cancer Hazard in Herbal Remedies: A Review. Mutagenesis, 17, 265-277.
https://doi.org/10.1093/mutage/17.4.265
[10]  Heinke, B., Tabea, Z., Kerstin, S., et al. (2019) Comparison of Aristolochic Acid I Derived DNA Adduct Levels in Human Renal Toxicity Models. Toxicology, 420, 29-38.
https://doi.org/10.1016/j.tox.2019.03.013
[11]  Dickman, K.G., Sweet, D.H., Bonala, R., et al. (2011) Physiological and Molecular Characterization of Aristolochic Acid Transport by the Kidney. The Journal of Pharmacology and Experimental Therapeutics, 338, 588-597.
https://doi.org/10.1124/jpet.111.180984
[12]  Graham, M.L., Rajat, T., Terry, C., et al. (1999) Nephropathy Caused by Chinese Herbs in the UK. The Lancet, 354, 481-482.
https://doi.org/10.1016/S0140-6736(99)03380-2
[13]  Liu, X.Y., Liu, Y.Q., Cheng, M.C., et al. (2015) Application of Ultra High Performance Liquid Chromatography-Mass Spectrometry to Metabolomics Study of Drug-Induced Hepatotoxicity. Chinese Journal of Chromatography, 33, 683-690.
https://doi.org/10.3724/SP.J.1123.2015.04007
[14]  Bhawani, D.J., Anubha, S., Vineet, G., et al. (2013) Spectroscopic and Quantum Chemical Study of an Alkaloid Aristolochic Acid I. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 116, 258-269.
https://doi.org/10.1016/j.saa.2013.07.036
[15]  Yoshiharu, O., Radha, B., Sivaprasad, A., et al. (2019) Bioactivation Mechanisms of N-Hydroxyaristolactams: Nitroreduction Metabolites of Aristolochic Acids. Environmental and Molecular Mutagenesis, 60, 792-806.
https://doi.org/10.1002/em.22321
[16]  Jadot, I., Declèves, A.E., Nortier, J., et al. (2017) An Integrated View of Aristolochic Acid Nephropathy: Update of the Literature. Molecular Science, 18, 297.
https://doi.org/10.3390/ijms18020297
[17]  Lord, G.M., Cook, T., Arlt, V.M., et al. (2001) Urothelial Malignant Disease and Chinese Herbal Nephropathy. The Lancet (London, England), 358, 1515-1516.
https://doi.org/10.1016/S0140-6736(01)06576-X
[18]  Kwak, D.H., Park, J.H., et al. (2014) Aristolochic Acid I Induces Ovarian Toxicity by Inhibition of AKT Phosphorylation. Chemical Research in Toxicology, 27, 2128-2135.
https://doi.org/10.1021/tx5003854
[19]  Zhang, Y., Yang, X.Y., Zhang, Y.W., et al. (2019) Exposure to Aristolochic Acid I Compromises the Maturational Competency of Porcine Oocytes via Oxidative Stress-Induced DNA Damage. Aging, 11, 2241-2252.
https://doi.org/10.18632/aging.101911
[20]  Wang, Y., Meng, F., Arlt, V.M., et al. (2011) Aristolochic Acid-Induced Carcinogenesis Examined by ACB-PCR Quantification of H-Ras and K-Ras Mutant Fraction. Mutagenesis, 26, 619-628.
https://doi.org/10.1093/mutage/ger023
[21]  Wang, L., Ding, X.S., Li, C.Y., et al. (2018) Oral Administration of Aristolochia manshuriensis Kom in Rats Induces Tumors in Multiple Organs. Journal of Ethnopharmacology, 225, 81-89.
https://doi.org/10.1016/j.jep.2018.07.001
[22]  Jin, K., Su, K.K., Li, T., et al. (2016) Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines. Cancer Prevention Research (Philadelphia, Pa.), 9, 324-334.
https://doi.org/10.1158/1940-6207.CAPR-15-0339
[23]  Wang, L.M., Zhang, H.B., Li, C.Y., et al. (2016) Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity. PLoS ONE, 11, e0164215.
https://doi.org/10.1371/journal.pone.0164215
[24]  应倩, 汪媛. 肝癌流行现况和趋势分析[J]. 中国肿瘤, 2020, 29(3): 185-191.
[25]  李玉. 马兜铃酸诱导的巨噬细胞极化对肝癌细胞迁移及侵袭作用初探[C]//中国中西医结合学会基础理论专业委员会. 第15届中国中西医结合学会基础理论专业委员会学术年会暨第二届广东省中西医结合学会转化医学专业委员会年会论文集. 中国中西医结合学会, 2019: 37-38.
[26]  Lu, Z.N., Luo, Q., Zhao, L.N., et al. (2019) The Mutational Features of Aristolochic Acid-Induced Mouse and Human Liver Cancers. Hepatology (Baltimore, Md.), 71, 929-942.
https://doi.org/10.1101/507301
[27]  Bhuban, R., Tapas, K.S., Kunal, P., et al. (2020) Herbometallic Nano-Drug Inducing Metastatic Growth Inhibition in Breast Cancer through Intracellular Energy Depletion. Molecular Biology Reports: An International Journal on Molecular and Cellular Biology, 47, 3745-3763.
https://doi.org/10.1007/s11033-020-05467-7
[28]  Kan, Z.Y., Zheng, H.C., Liu, X., et al. (2013) Whole-Genome Sequencing Identifies Recurrent Mutations in Hepatocellular Carcinoma. Genome Research, 23, 1422-1433.
[29]  Lin, D.C., Mayakonda, A., Dinh, H.Q., et al. (2017) Genomic and Epigenomic Heterogeneity of Hepatocellular Carcinoma. Cancer Research, 77, 2255-2265.
https://doi.org/10.1158/0008-5472.CAN-16-2822
[30]  Cancer Genome Atlas Research Network (2017) Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell, 169, 1327-1341.e23.
[31]  Eric, L., Jayendra, S., Victor, R., et al. (2017) Mutational Signatures Reveal the Dynamic Interplay of Risk Factors and Cellular Processes during Liver Tumorigenesis. Nature Communications, 8, Article No. 1315.
https://doi.org/10.1038/s41467-017-01358-x
[32]  Fujimoto, A., Furuta, M., Totoki, Y., et al. (2016) Whole-Genome Mutational Landscape and Characterization of Noncoding and Structural Mutations in Liver Cancer. Nature Genetics, 48, 500-509.
[33]  Yasushi, T., Kenji, T., Kyle, R.C., et al. (2014) Trans-Ancestry Mutational Landscape of Hepatocellular Carcinoma Genomes. Nature Genetics, 46, 1267-1273.
[34]  Zhai, W.W., Lim, T.K.H., Zhang, T., et al. (2017) The Spatial Organization of Intra-Tumour Heterogeneity and Evolutionary Trajectories of Metastases in Hepatocellular Carcinoma. Nature Communications, 8, Article No. 4565.
https://doi.org/10.1038/ncomms14565
[35]  Ahn, S.M., Jang, S.J., Shim, J.H., et al. (2014) Genomic Portrait of Resectable Hepatocellular Carcinomas: Implications of RB1 and FGF19 Aberrations for Patient Stratification. Hepatology, 60, 1972-1982.
https://doi.org/10.1002/hep.27198
[36]  Zou, S.S., Li, J.R., Zhou, H.B., et al. (2014) Mutational Landscape of Intrahepatic Cholangiocarcinoma. Nature Communications, 5, Article No. 5696.
https://doi.org/10.1038/ncomms6696
[37]  Xue, R.D., Chen, L., Zhang, C., et al. (2019) Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes. Cancer Cell, 35, 932-947.
https://doi.org/10.1016/j.ccell.2019.04.007
[38]  Debelle, F.D., Vanherweghem, J.L. and Nortier, J.L. (2008) Aristolochic Acid Nephropathy: A Worldwide Problem. Kidney International, 74, 158-169.
https://doi.org/10.1038/ki.2008.129
[39]  Kim, J.Y., Leem, J. and Jeon, E.J. (2019) Protective Effects of Melatonin against Aristolochic Acid-Induced Nephropathy in Mice. Biomolecules, 10, 11.
https://doi.org/10.3390/biom10010011
[40]  Arlt, V.M., Stiborova, M., vom Brocke, J., et al. (2007) Aristolochic Acid Mutagenesis: Molecular Clues to the Aetiology of Balkan Endemic Nephropathy-Associated Urothelial Cancer. Carcinogenesis, 28, 2253-2261.
https://doi.org/10.1093/carcin/bgm082
[41]  Stiborova, M., Frei, E., Sopko, B., et al. (2003) Human Cytosolic Enzymes Involved in the Metabolic Activation of Carcinogenic Aristolochic Acid: Evidence for Reductive Activation by Human NAD(P)H: Quinone Oxidoreductase. Carcinogenesis, 24, 1695-1703.
https://doi.org/10.1093/carcin/bgg119
[42]  Stiborova, M., Barta, F., Levova, K., et al. (2015) A Mechanism of O-Demethylation of Aristolochic Acid I by Cytochromes P450 and Their Contributions to This Reaction in Human and Rat Livers: Experimental and Theoretical Approaches. International Journal of Molecular Sciences, 16, 27561-27575.
https://doi.org/10.3390/ijms161126047
[43]  Stiborova, M., Frei, E., Arlt, V.M., et al. (2008) Metabolic Activation of Carcinogenic Aristolochic Acid, a Risk Factor for Balkan Endemic Nephropathy. Mutation Research, 658, 55-67.
https://doi.org/10.1016/j.mrrev.2007.07.003
[44]  Milichovsky, J., Barta, F., Schmeiser, H.H., et al. (2016) Active Site Mutations as a Suitable Tool Contributing to Explain a Mechanism of Aristolochic Acid I Nitroreduction by Cytochromes P450 1A1, 1A2 and 1B1. International Journal of Molecular Sciences, 17, 213.
https://doi.org/10.3390/ijms17020213
[45]  周伟敏. PDK1通过PI3K/AKT信号通路介导肾细胞癌生物学行为及机制研究[D]: [博士学位论文]. 南昌: 南昌大学, 2019.
[46]  Yang, L., Li, X.M., Wang, S.X., et al. (2005) Peritubular Capillary Injury in Chinese Herb Guan-Mu-Tong-Induced Acute Tubular Necrosis. Chinese Journal of Internal Medicine, 44, 525-529.
[47]  Dimmeler, S. and Zeiher, A.M. (2000) Akt Takes Center Stage in Angiogenesis Signaling. Circulation Research, 86, 4-5.
https://doi.org/10.1161/01.RES.86.1.4
[48]  Shi, H. and Feng, J.M. (2011) Aristolochic Acid Induces Apoptosis of Human Umbilical Vein Endothelial Cells in Vitro by Suppressing PI3K/Akt Signaling Pathway. Acta Pharmaceutica Sinica, 32, 1025-1030.
https://doi.org/10.1038/aps.2011.74
[49]  杨召聪, 陆茵, 顾亚琴, 等. 马兜铃酸I对大鼠体内PI3K/Akt/NF-κB通路的影响κ[J]. 南京中医药大学学报, 2015, 31(3): 250-253.
[50]  Einar, S.B., Ottar, M., Bergmann, H.K., et al. (2013) Incidence, Presentation, and Outcomes in Patients with Drug-Induced Liver Injury in the General Population of Iceland. Gastroenterology, 144, 1419-1425.
https://doi.org/10.1053/j.gastro.2013.04.042
[51]  Liu, X.Y., Liu, Y.Q., Cheng, M.C., et al. (2015) Metabolomic Responses of Human Hepatocytes to Emodin, Aristolochic Acid, and Triptolide: Chemicals Purified from Traditional Chinese Medicines. Journal of Biochemical and Molecular Toxicology, 29, 533-543.
https://doi.org/10.1002/jbt.21724
[52]  Davies, L., Fassbender, K. and Walter, S. (2013) Sphingolipids in Disease. In: Sphingolipids in Neuroinflammation, Vol. 216 of Handbook of Experimental Pharmacology, Springer, Berlin, 421-430.
https://doi.org/10.1007/978-3-7091-1511-4_21
[53]  Roe, D.S., Yang, B.Z., Vianey-Saban, C., et al. (2006) Differentiation of Long-Chain Fatty Acid Oxidation Disorders Using Alternative Precursors and Acylcarnitine Profiling in Fibroblasts. Molecular Genetics and Metabolism, 87, 40-47.
https://doi.org/10.1016/j.ymgme.2005.09.018
[54]  Sessa, A. and Perin, A. (1991) Increased Synthesis of N1-Acetylspermidine in Hepatic Preneoplastic Nodules and Hepatomas. Cancer Letters, 56, 159-163.
https://doi.org/10.1016/0304-3835(91)90091-U

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133