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Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents

Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates...

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Autores principales: Li, Xi-Lin, Guo, Xiao-Qing, Wang, Hai-Rong, Chen, Tao, Mei, Nan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110418/
https://www.ncbi.nlm.nih.gov/pubmed/32258091
http://dx.doi.org/10.4103/wjtcm.wjtcm_33_19
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author Li, Xi-Lin
Guo, Xiao-Qing
Wang, Hai-Rong
Chen, Tao
Mei, Nan
author_facet Li, Xi-Lin
Guo, Xiao-Qing
Wang, Hai-Rong
Chen, Tao
Mei, Nan
author_sort Li, Xi-Lin
collection PubMed
description Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates that AA is nephrotoxic, genotoxic, and carcinogenic in humans; and it also induces tumors in the forestomach, kidney, renal pelvis, urinary bladder, and lung of rats and mice. Therefore, plants containing AA have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. In our laboratories, we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 weeks. Our results demonstrated that AA treatments induced DNA adducts and mutations in the kidney, liver, and spleen of rats, as well as significant alteration of gene expression in both its target and nontarget tissues. AA treatments altered mutagenesis- or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression profiling. We also applied benchmark dose (BMD) modeling to the 3-month AA-induced genotoxicity data. The obtained BMDL(10) (the lower 95% confidence interval of the BMD(10) that is a 10% increase over the background level) for AA-induced mutations in the kidney of rats was about 7 μg/kg body weight per day. This review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression, microRNA expression, and proteomics; and presents updated information focused on AA-induced genotoxicity in rodents.
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spelling pubmed-71104182020-04-01 Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents Li, Xi-Lin Guo, Xiao-Qing Wang, Hai-Rong Chen, Tao Mei, Nan World J Tradit Chin Med Article Aristolochic acid (AA) is a group of structurally related nitrophenanthrene carboxylic acids found in many plants that are widely used by many cultures as traditional herbal medicines. AA is a causative agent for Chinese herbs nephropathy, a term replaced later by AA nephropathy. Evidence indicates that AA is nephrotoxic, genotoxic, and carcinogenic in humans; and it also induces tumors in the forestomach, kidney, renal pelvis, urinary bladder, and lung of rats and mice. Therefore, plants containing AA have been classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. In our laboratories, we have conducted a series of genotoxicity and toxicogenomic studies in the rats exposed to AA of 0.1–10 mg/kg for 12 weeks. Our results demonstrated that AA treatments induced DNA adducts and mutations in the kidney, liver, and spleen of rats, as well as significant alteration of gene expression in both its target and nontarget tissues. AA treatments altered mutagenesis- or carcinogenesis-related microRNA expression in rat kidney and resulted in significant changes in protein expression profiling. We also applied benchmark dose (BMD) modeling to the 3-month AA-induced genotoxicity data. The obtained BMDL(10) (the lower 95% confidence interval of the BMD(10) that is a 10% increase over the background level) for AA-induced mutations in the kidney of rats was about 7 μg/kg body weight per day. This review constitutes an overview of our investigations on AA-induced genotoxicity and toxicogenomic changes including gene expression, microRNA expression, and proteomics; and presents updated information focused on AA-induced genotoxicity in rodents. 2020-03-13 2020 /pmc/articles/PMC7110418/ /pubmed/32258091 http://dx.doi.org/10.4103/wjtcm.wjtcm_33_19 Text en http://creativecommons.org/licenses/by/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Article
Li, Xi-Lin
Guo, Xiao-Qing
Wang, Hai-Rong
Chen, Tao
Mei, Nan
Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents
title Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents
title_full Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents
title_fullStr Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents
title_full_unstemmed Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents
title_short Aristolochic Acid-Induced Genotoxicity and Toxicogenomic Changes in Rodents
title_sort aristolochic acid-induced genotoxicity and toxicogenomic changes in rodents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110418/
https://www.ncbi.nlm.nih.gov/pubmed/32258091
http://dx.doi.org/10.4103/wjtcm.wjtcm_33_19
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