Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches
Aristolochic acid (AA) is a generic term that describes a group of structurally related compounds found in the Aristolochiaceae plants family. These plants have been used for decades to treat various diseases. However, the consumption of products derived from plants containing AA has been associated...
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| Veröffentlicht in: | International journal of molecular sciences 2020-02, Vol.21 (3), p.1157 |
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| description | Aristolochic acid (AA) is a generic term that describes a group of structurally related compounds found in the Aristolochiaceae plants family. These plants have been used for decades to treat various diseases. However, the consumption of products derived from plants containing AA has been associated with the development of nephropathy and carcinoma, mainly the upper urothelial carcinoma (UUC). AA has been identified as the causative agent of these pathologies. Several studies on mechanisms of action of AA nephrotoxicity have been conducted, but the comprehensive mechanisms of AA-induced nephrotoxicity and carcinogenesis have not yet fully been elucidated, and therapeutic measures are therefore limited. This review aimed to summarize the molecular mechanisms underlying AA-induced nephrotoxicity with an emphasis on its enzymatic bioactivation, and to discuss some agents and their modes of action to reduce AA nephrotoxicity. By addressing these two aspects, including mechanisms of action of AA nephrotoxicity and protective approaches against the latter, and especially by covering the whole range of these protective agents, this review provides an overview on AA nephrotoxicity. It also reports new knowledge on mechanisms of AA-mediated nephrotoxicity recently published in the literature and provides suggestions for future studies. |
| doi_str_mv | 10.3390/ijms21031157 |
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These plants have been used for decades to treat various diseases. However, the consumption of products derived from plants containing AA has been associated with the development of nephropathy and carcinoma, mainly the upper urothelial carcinoma (UUC). AA has been identified as the causative agent of these pathologies. Several studies on mechanisms of action of AA nephrotoxicity have been conducted, but the comprehensive mechanisms of AA-induced nephrotoxicity and carcinogenesis have not yet fully been elucidated, and therapeutic measures are therefore limited. This review aimed to summarize the molecular mechanisms underlying AA-induced nephrotoxicity with an emphasis on its enzymatic bioactivation, and to discuss some agents and their modes of action to reduce AA nephrotoxicity. By addressing these two aspects, including mechanisms of action of AA nephrotoxicity and protective approaches against the latter, and especially by covering the whole range of these protective agents, this review provides an overview on AA nephrotoxicity. It also reports new knowledge on mechanisms of AA-mediated nephrotoxicity recently published in the literature and provides suggestions for future studies.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21031157</identifier><identifier>PMID: 32050524</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acids ; Animals ; Aristolochic acid ; Aristolochic Acids - toxicity ; Bladder cancer ; Carcinogenesis ; Carcinogens ; Carcinogens - toxicity ; DNA Adducts ; Enzymes ; Flowers & plants ; Humans ; Kidney diseases ; Kidney Neoplasms - chemically induced ; Kidney Neoplasms - prevention & control ; Metabolism ; Metabolites ; Molecular modelling ; Mutagens - toxicity ; Mutation ; Nephropathy ; Review ; Toxicity ; Tumor Suppressor Protein p53 - genetics ; Urothelial carcinoma</subject><ispartof>International journal of molecular sciences, 2020-02, Vol.21 (3), p.1157</ispartof><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-5b51204a442e26b6de91be871b2cace34cd5d83653e9d542e8c18a91b60e98f03</citedby><cites>FETCH-LOGICAL-c478t-5b51204a442e26b6de91be871b2cace34cd5d83653e9d542e8c18a91b60e98f03</cites><orcidid>0000-0002-2931-798X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043226/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043226/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32050524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anger, Etienne Empweb</creatorcontrib><creatorcontrib>Yu, Feng</creatorcontrib><creatorcontrib>Li, Ji</creatorcontrib><title>Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Aristolochic acid (AA) is a generic term that describes a group of structurally related compounds found in the Aristolochiaceae plants family. These plants have been used for decades to treat various diseases. However, the consumption of products derived from plants containing AA has been associated with the development of nephropathy and carcinoma, mainly the upper urothelial carcinoma (UUC). AA has been identified as the causative agent of these pathologies. Several studies on mechanisms of action of AA nephrotoxicity have been conducted, but the comprehensive mechanisms of AA-induced nephrotoxicity and carcinogenesis have not yet fully been elucidated, and therapeutic measures are therefore limited. This review aimed to summarize the molecular mechanisms underlying AA-induced nephrotoxicity with an emphasis on its enzymatic bioactivation, and to discuss some agents and their modes of action to reduce AA nephrotoxicity. By addressing these two aspects, including mechanisms of action of AA nephrotoxicity and protective approaches against the latter, and especially by covering the whole range of these protective agents, this review provides an overview on AA nephrotoxicity. It also reports new knowledge on mechanisms of AA-mediated nephrotoxicity recently published in the literature and provides suggestions for future studies.</description><subject>Acids</subject><subject>Animals</subject><subject>Aristolochic acid</subject><subject>Aristolochic Acids - toxicity</subject><subject>Bladder cancer</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Carcinogens - toxicity</subject><subject>DNA Adducts</subject><subject>Enzymes</subject><subject>Flowers & plants</subject><subject>Humans</subject><subject>Kidney diseases</subject><subject>Kidney Neoplasms - chemically induced</subject><subject>Kidney Neoplasms - prevention & control</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Molecular modelling</subject><subject>Mutagens - toxicity</subject><subject>Mutation</subject><subject>Nephropathy</subject><subject>Review</subject><subject>Toxicity</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Urothelial carcinoma</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVkUtLAzEURoMoVqs71zLg1tE85-FCKMVHwWoXug6Z5NZJmU7GJCP67x1RS13dC_fw3Q8OQicEXzBW4ku7WgdKMCNE5DvogHBKU4yzfHdrH6HDEFYYU0ZFuY9GjGKBBeUHqJp4G6JrnK6tTibamnTWml6DSR6hq72L7sNqGz-vkrlrQPeN8skcdK1aG9YhUa1JFi5CG61qksXAg472HZJJ13mndA3hCO0tVRPg-HeO0cvtzfP0Pn14uptNJw-p5nkRU1EJQjFXnFOgWZUZKEkFRU4qqpUGxrURpmCZYFAaMUCFJoUamAxDWSwxG6Prn9yur9Zg9NDJq0Z23q6V_5ROWfn_0tpavrp3mWPOKM2GgLPfAO_eeghRrlzv26GzpIIXWSmykg7U-Q-lvQvBw3LzgWD5bURuGxnw0-1WG_hPAfsCYtCJWg</recordid><startdate>20200210</startdate><enddate>20200210</enddate><creator>Anger, Etienne Empweb</creator><creator>Yu, Feng</creator><creator>Li, Ji</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2931-798X</orcidid></search><sort><creationdate>20200210</creationdate><title>Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches</title><author>Anger, Etienne Empweb ; Yu, Feng ; Li, Ji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-5b51204a442e26b6de91be871b2cace34cd5d83653e9d542e8c18a91b60e98f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acids</topic><topic>Animals</topic><topic>Aristolochic acid</topic><topic>Aristolochic Acids - toxicity</topic><topic>Bladder cancer</topic><topic>Carcinogenesis</topic><topic>Carcinogens</topic><topic>Carcinogens - toxicity</topic><topic>DNA Adducts</topic><topic>Enzymes</topic><topic>Flowers & plants</topic><topic>Humans</topic><topic>Kidney diseases</topic><topic>Kidney Neoplasms - chemically induced</topic><topic>Kidney Neoplasms - prevention & control</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Molecular modelling</topic><topic>Mutagens - toxicity</topic><topic>Mutation</topic><topic>Nephropathy</topic><topic>Review</topic><topic>Toxicity</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Urothelial carcinoma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anger, Etienne Empweb</creatorcontrib><creatorcontrib>Yu, Feng</creatorcontrib><creatorcontrib>Li, Ji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anger, Etienne Empweb</au><au>Yu, Feng</au><au>Li, Ji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-02-10</date><risdate>2020</risdate><volume>21</volume><issue>3</issue><spage>1157</spage><pages>1157-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Aristolochic acid (AA) is a generic term that describes a group of structurally related compounds found in the Aristolochiaceae plants family. These plants have been used for decades to treat various diseases. However, the consumption of products derived from plants containing AA has been associated with the development of nephropathy and carcinoma, mainly the upper urothelial carcinoma (UUC). AA has been identified as the causative agent of these pathologies. Several studies on mechanisms of action of AA nephrotoxicity have been conducted, but the comprehensive mechanisms of AA-induced nephrotoxicity and carcinogenesis have not yet fully been elucidated, and therapeutic measures are therefore limited. This review aimed to summarize the molecular mechanisms underlying AA-induced nephrotoxicity with an emphasis on its enzymatic bioactivation, and to discuss some agents and their modes of action to reduce AA nephrotoxicity. By addressing these two aspects, including mechanisms of action of AA nephrotoxicity and protective approaches against the latter, and especially by covering the whole range of these protective agents, this review provides an overview on AA nephrotoxicity. It also reports new knowledge on mechanisms of AA-mediated nephrotoxicity recently published in the literature and provides suggestions for future studies.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32050524</pmid><doi>10.3390/ijms21031157</doi><orcidid>https://orcid.org/0000-0002-2931-798X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Animals Aristolochic acid Aristolochic Acids - toxicity Bladder cancer Carcinogenesis Carcinogens Carcinogens - toxicity DNA Adducts Enzymes Flowers & plants Humans Kidney diseases Kidney Neoplasms - chemically induced Kidney Neoplasms - prevention & control Metabolism Metabolites Molecular modelling Mutagens - toxicity Mutation Nephropathy Review Toxicity Tumor Suppressor Protein p53 - genetics Urothelial carcinoma |
| title | Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches |
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