Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae
To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the...
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| Veröffentlicht in: | Human & experimental toxicology 2016-09, Vol.35 (9), p.974-982 |
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| creator | Wang, X Liu, K-C Sun, G-J Han, L-W Wang, R-C Peng, W-B Sun, C Hsiao, C-D Zhang, Y Hou, H-R |
| description | To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the larvae treated with 10 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography–mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose-dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate–polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 µmoL/L AA-treated groups decreased to 0.58 ± 0.062 and 0.37 ± 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose-dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria. |
| doi_str_mv | 10.1177/0960327115613844 |
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It was found that 21% of the larvae treated with 10 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography–mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose-dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate–polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 µmoL/L AA-treated groups decreased to 0.58 ± 0.062 and 0.37 ± 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose-dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria.</description><identifier>ISSN: 0960-3271</identifier><identifier>EISSN: 1477-0903</identifier><identifier>DOI: 10.1177/0960327115613844</identifier><identifier>PMID: 26612554</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Aristolochic acid ; Aristolochic Acids - toxicity ; Blood flow ; Cardiovascular system ; Creatinine ; Creatinine - metabolism ; Damage ; Danio rerio ; Edema ; Electrophoresis ; Embryo, Nonmammalian - drug effects ; Embryo, Nonmammalian - metabolism ; Embryo, Nonmammalian - pathology ; Filtration ; Gel electrophoresis ; Gene expression ; Heart ; Injuries ; Kidney - drug effects ; Kidney - embryology ; Kidney - metabolism ; Kidney - pathology ; Kidneys ; Larva ; Larvae ; Leakage ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Paraffin ; Polymerase chain reaction ; Proteinuria ; Proteinuria - chemically induced ; Proteinuria - embryology ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; Scientific imaging ; Sodium ; Sodium dodecyl sulfate ; Sulfates ; Toxicity ; Tubules ; Zebrafish ; Zebrafish - growth & development ; Zebrafish - metabolism</subject><ispartof>Human & experimental toxicology, 2016-09, Vol.35 (9), p.974-982</ispartof><rights>The Author(s) 2015</rights><rights>The Author(s) 2015.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c464t-2858562d921cb4c46fdff8376bdcefcdc6c6100ebb888d95690a0aa678255e4f3</citedby><cites>FETCH-LOGICAL-c464t-2858562d921cb4c46fdff8376bdcefcdc6c6100ebb888d95690a0aa678255e4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0960327115613844$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0960327115613844$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21966,27853,27924,27925,44945,45333</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/0960327115613844?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26612554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, X</creatorcontrib><creatorcontrib>Liu, K-C</creatorcontrib><creatorcontrib>Sun, G-J</creatorcontrib><creatorcontrib>Han, L-W</creatorcontrib><creatorcontrib>Wang, R-C</creatorcontrib><creatorcontrib>Peng, W-B</creatorcontrib><creatorcontrib>Sun, C</creatorcontrib><creatorcontrib>Hsiao, C-D</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>Hou, H-R</creatorcontrib><title>Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae</title><title>Human & experimental toxicology</title><addtitle>Hum Exp Toxicol</addtitle><description>To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the larvae treated with 10 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography–mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose-dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate–polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 µmoL/L AA-treated groups decreased to 0.58 ± 0.062 and 0.37 ± 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose-dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria.</description><subject>Animals</subject><subject>Aristolochic acid</subject><subject>Aristolochic Acids - toxicity</subject><subject>Blood flow</subject><subject>Cardiovascular system</subject><subject>Creatinine</subject><subject>Creatinine - metabolism</subject><subject>Damage</subject><subject>Danio rerio</subject><subject>Edema</subject><subject>Electrophoresis</subject><subject>Embryo, Nonmammalian - drug effects</subject><subject>Embryo, Nonmammalian - metabolism</subject><subject>Embryo, Nonmammalian - pathology</subject><subject>Filtration</subject><subject>Gel electrophoresis</subject><subject>Gene expression</subject><subject>Heart</subject><subject>Injuries</subject><subject>Kidney - drug effects</subject><subject>Kidney - embryology</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidneys</subject><subject>Larva</subject><subject>Larvae</subject><subject>Leakage</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Paraffin</subject><subject>Polymerase chain reaction</subject><subject>Proteinuria</subject><subject>Proteinuria - chemically induced</subject><subject>Proteinuria - embryology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Scientific imaging</subject><subject>Sodium</subject><subject>Sodium dodecyl sulfate</subject><subject>Sulfates</subject><subject>Toxicity</subject><subject>Tubules</subject><subject>Zebrafish</subject><subject>Zebrafish - growth & development</subject><subject>Zebrafish - metabolism</subject><issn>0960-3271</issn><issn>1477-0903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1LAzEQxYMotlbvnmTBSz2sZrLZJHuUWj9A8KLgbclmE5uy3dRkt6h_vSmtIgVPA29-8-bxEDoFfAnA-RUuGM4IB8gZZILSPTQEynmKC5zto-F6na73A3QUwhxjzIocDtGAMAYkz-kQvU5XsullZ12bOJO0ejnzrnMfViXaGK26sJalt6FzjVOzqEtl6yTiX7ry0tgwS8Y3srUu8dpbd5E00q-kPkYHRjZBn2znCL3cTp8n9-nj093D5PoxVZTRLiUiFzkjdUFAVTRqpjZGZJxVtdJG1YopBhjrqhJC1EXOCiyxlIyLmF9Tk43QeOO79O6916ErFzYo3TSy1a4PJQgAIZjgIqLnO-jc9b6N6UoogBDIMLBI4Q2lvAvBa1MuvV1I_1kCLtetl7utx5OzrXFfLXT9e_BTcwTSDRDkm_7z9T_Db80AiNk</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Wang, X</creator><creator>Liu, K-C</creator><creator>Sun, G-J</creator><creator>Han, L-W</creator><creator>Wang, R-C</creator><creator>Peng, W-B</creator><creator>Sun, C</creator><creator>Hsiao, C-D</creator><creator>Zhang, Y</creator><creator>Hou, H-R</creator><general>SAGE Publications</general><general>Sage Publications Ltd</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>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>SOI</scope></search><sort><creationdate>20160901</creationdate><title>Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae</title><author>Wang, X ; Liu, K-C ; Sun, G-J ; Han, L-W ; Wang, R-C ; Peng, W-B ; Sun, C ; Hsiao, C-D ; Zhang, Y ; Hou, H-R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c464t-2858562d921cb4c46fdff8376bdcefcdc6c6100ebb888d95690a0aa678255e4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Aristolochic acid</topic><topic>Aristolochic Acids - toxicity</topic><topic>Blood flow</topic><topic>Cardiovascular system</topic><topic>Creatinine</topic><topic>Creatinine - metabolism</topic><topic>Damage</topic><topic>Danio rerio</topic><topic>Edema</topic><topic>Electrophoresis</topic><topic>Embryo, Nonmammalian - drug effects</topic><topic>Embryo, Nonmammalian - metabolism</topic><topic>Embryo, Nonmammalian - pathology</topic><topic>Filtration</topic><topic>Gel electrophoresis</topic><topic>Gene expression</topic><topic>Heart</topic><topic>Injuries</topic><topic>Kidney - drug effects</topic><topic>Kidney - embryology</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidneys</topic><topic>Larva</topic><topic>Larvae</topic><topic>Leakage</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Paraffin</topic><topic>Polymerase chain reaction</topic><topic>Proteinuria</topic><topic>Proteinuria - chemically induced</topic><topic>Proteinuria - embryology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Scientific imaging</topic><topic>Sodium</topic><topic>Sodium dodecyl sulfate</topic><topic>Sulfates</topic><topic>Toxicity</topic><topic>Tubules</topic><topic>Zebrafish</topic><topic>Zebrafish - growth & development</topic><topic>Zebrafish - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, X</creatorcontrib><creatorcontrib>Liu, K-C</creatorcontrib><creatorcontrib>Sun, G-J</creatorcontrib><creatorcontrib>Han, L-W</creatorcontrib><creatorcontrib>Wang, R-C</creatorcontrib><creatorcontrib>Peng, W-B</creatorcontrib><creatorcontrib>Sun, C</creatorcontrib><creatorcontrib>Hsiao, C-D</creatorcontrib><creatorcontrib>Zhang, Y</creatorcontrib><creatorcontrib>Hou, H-R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Environment Abstracts</collection><jtitle>Human & experimental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Wang, X</au><au>Liu, K-C</au><au>Sun, G-J</au><au>Han, L-W</au><au>Wang, R-C</au><au>Peng, W-B</au><au>Sun, C</au><au>Hsiao, C-D</au><au>Zhang, Y</au><au>Hou, H-R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae</atitle><jtitle>Human & experimental toxicology</jtitle><addtitle>Hum Exp Toxicol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>35</volume><issue>9</issue><spage>974</spage><epage>982</epage><pages>974-982</pages><issn>0960-3271</issn><eissn>1477-0903</eissn><abstract>To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the larvae treated with 10 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography–mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose-dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate–polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 µmoL/L AA-treated groups decreased to 0.58 ± 0.062 and 0.37 ± 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose-dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>26612554</pmid><doi>10.1177/0960327115613844</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Aristolochic acid Aristolochic Acids - toxicity Blood flow Cardiovascular system Creatinine Creatinine - metabolism Damage Danio rerio Edema Electrophoresis Embryo, Nonmammalian - drug effects Embryo, Nonmammalian - metabolism Embryo, Nonmammalian - pathology Filtration Gel electrophoresis Gene expression Heart Injuries Kidney - drug effects Kidney - embryology Kidney - metabolism Kidney - pathology Kidneys Larva Larvae Leakage Liquid chromatography Mass spectrometry Mass spectroscopy Paraffin Polymerase chain reaction Proteinuria Proteinuria - chemically induced Proteinuria - embryology Reverse Transcriptase Polymerase Chain Reaction Ribonucleic acid RNA Scientific imaging Sodium Sodium dodecyl sulfate Sulfates Toxicity Tubules Zebrafish Zebrafish - growth & development Zebrafish - metabolism |
| title | Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae |
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