Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling
Both melamine and cyanuric acid have low toxicity, but combined exposure to melamine and cyanuric acid (M + CA) was reported to cause unexpected toxicological synergy on kidney damage. In this study, we investigated the role of oxidative stress and apoptotic changes in the nephrotoxicity caused by M...
Gespeichert in:
| Veröffentlicht in: | Food and chemical toxicology 2016-10, Vol.96, p.254-262 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 262 |
|---|---|
| container_issue | |
| container_start_page | 254 |
| container_title | Food and chemical toxicology |
| container_volume | 96 |
| creator | Lee, In-Chul Ko, Je-Won Park, Sung-Hyeuk Shin, In-Sik Moon, Changjong Kim, Sung-Ho Kim, Yun-Bae Kim, Jong-Choon |
| description | Both melamine and cyanuric acid have low toxicity, but combined exposure to melamine and cyanuric acid (M + CA) was reported to cause unexpected toxicological synergy on kidney damage. In this study, we investigated the role of oxidative stress and apoptotic changes in the nephrotoxicity caused by M + CA in rats. M + CA treatment caused an increase in the kidney weight, serum blood urea nitrogen or creatinine levels in a dose-dependent manner. With severe morphological and histological changes in kidneys, M + CA markedly elevated lipid peroxidation and suppressed antioxidant enzyme activities. M + CA treatment induced apoptotic changes in renal tubular cells. Additionally, exposure to M + CA increased phosphorylation of mitogen-activated protein kinases (MAPKs) coincided with increased Bax level and decreased Bcl2 level, resulting in caspase-3 activation. In summary, oxidative stress and simultaneous MAPKs and mitochondrial/caspase activation may be related to renal tubular cell apoptosis caused by M + CA.
•M + CA caused functional and histopathological alteration in the kidneys.•M + CA increased lipid peroxidation and decreased antioxidant enzyme activities in the kidneys.•M + CA induced renal tubular cell apoptotic changes in the kidneys.•M + CA caused phosphorylation of mitogen-activated protein kinases (MAPKs).•M + CA increased Bax and decreased Bcl2 levels with caspase-3 activation in the kidneys. |
| doi_str_mv | 10.1016/j.fct.2016.08.013 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1827910541</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0278691516302794</els_id><sourcerecordid>1827910541</sourcerecordid><originalsourceid>FETCH-LOGICAL-c386t-fdb575b90cf6e56de16cdde1da7518895a06b050eb56d195629630a835e097173</originalsourceid><addsrcrecordid>eNp9kEFP3DAQha0K1F1of0AvKEcuScdJ7TjqCSHaoi6CAz1bjj3ZepXYWztGXfHn8bLAkct4rPfeJ80j5AuFigLlXzfVoOeqzmsFogLafCBLKtqm5A2jR2QJdStK3lG2ICcxbgCgpS3_SBZ1y-qm7uolebzBUU3WYaGcKfROuRSsLpS2-edL_L_1MQUstEoRYxHQqbEwuzgkp2fr3XMsziHpOYW9pCa1xuLBquLm4u53fNYnO3v91zsTbLZEu84Q69afyPGgxoifX95T8ufH1f3lr3J1-_P68mJV6kbwuRxMz1rWd6AHjowbpFybPI1qGRWiYwp4DwywzyLtGK873oASDUPo8sHNKTk_cLfB_0sYZznZqHEclUOfoqSibjsK7BvNVnqw6uBjDDjIbbCTCjtJQe47lxuZO5f7ziUImTvPmbMXfOonNG-J15Kz4fvBgPnIB4tBRm3RaTQ2YIYZb9_BPwEsLZNi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1827910541</pqid></control><display><type>article</type><title>Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Lee, In-Chul ; Ko, Je-Won ; Park, Sung-Hyeuk ; Shin, In-Sik ; Moon, Changjong ; Kim, Sung-Ho ; Kim, Yun-Bae ; Kim, Jong-Choon</creator><creatorcontrib>Lee, In-Chul ; Ko, Je-Won ; Park, Sung-Hyeuk ; Shin, In-Sik ; Moon, Changjong ; Kim, Sung-Ho ; Kim, Yun-Bae ; Kim, Jong-Choon</creatorcontrib><description>Both melamine and cyanuric acid have low toxicity, but combined exposure to melamine and cyanuric acid (M + CA) was reported to cause unexpected toxicological synergy on kidney damage. In this study, we investigated the role of oxidative stress and apoptotic changes in the nephrotoxicity caused by M + CA in rats. M + CA treatment caused an increase in the kidney weight, serum blood urea nitrogen or creatinine levels in a dose-dependent manner. With severe morphological and histological changes in kidneys, M + CA markedly elevated lipid peroxidation and suppressed antioxidant enzyme activities. M + CA treatment induced apoptotic changes in renal tubular cells. Additionally, exposure to M + CA increased phosphorylation of mitogen-activated protein kinases (MAPKs) coincided with increased Bax level and decreased Bcl2 level, resulting in caspase-3 activation. In summary, oxidative stress and simultaneous MAPKs and mitochondrial/caspase activation may be related to renal tubular cell apoptosis caused by M + CA.
•M + CA caused functional and histopathological alteration in the kidneys.•M + CA increased lipid peroxidation and decreased antioxidant enzyme activities in the kidneys.•M + CA induced renal tubular cell apoptotic changes in the kidneys.•M + CA caused phosphorylation of mitogen-activated protein kinases (MAPKs).•M + CA increased Bax and decreased Bcl2 levels with caspase-3 activation in the kidneys.</description><identifier>ISSN: 0278-6915</identifier><identifier>EISSN: 1873-6351</identifier><identifier>DOI: 10.1016/j.fct.2016.08.013</identifier><identifier>PMID: 27523292</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antioxidants - metabolism ; Apoptosis ; Body Weight - drug effects ; Cyanuric acid ; Dose-Response Relationship, Drug ; Drug Combinations ; Female ; Glutathione - metabolism ; Immunoblotting ; Kidney Diseases - drug therapy ; Kidney Diseases - etiology ; Kidney Diseases - metabolism ; Kidney Diseases - pathology ; Lipid Peroxidation - drug effects ; Melamine ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitogen-activated protein kinases ; Mitogen-Activated Protein Kinases - metabolism ; Nephrotoxicity ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Triazines - toxicity</subject><ispartof>Food and chemical toxicology, 2016-10, Vol.96, p.254-262</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-fdb575b90cf6e56de16cdde1da7518895a06b050eb56d195629630a835e097173</citedby><cites>FETCH-LOGICAL-c386t-fdb575b90cf6e56de16cdde1da7518895a06b050eb56d195629630a835e097173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.fct.2016.08.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27523292$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, In-Chul</creatorcontrib><creatorcontrib>Ko, Je-Won</creatorcontrib><creatorcontrib>Park, Sung-Hyeuk</creatorcontrib><creatorcontrib>Shin, In-Sik</creatorcontrib><creatorcontrib>Moon, Changjong</creatorcontrib><creatorcontrib>Kim, Sung-Ho</creatorcontrib><creatorcontrib>Kim, Yun-Bae</creatorcontrib><creatorcontrib>Kim, Jong-Choon</creatorcontrib><title>Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling</title><title>Food and chemical toxicology</title><addtitle>Food Chem Toxicol</addtitle><description>Both melamine and cyanuric acid have low toxicity, but combined exposure to melamine and cyanuric acid (M + CA) was reported to cause unexpected toxicological synergy on kidney damage. In this study, we investigated the role of oxidative stress and apoptotic changes in the nephrotoxicity caused by M + CA in rats. M + CA treatment caused an increase in the kidney weight, serum blood urea nitrogen or creatinine levels in a dose-dependent manner. With severe morphological and histological changes in kidneys, M + CA markedly elevated lipid peroxidation and suppressed antioxidant enzyme activities. M + CA treatment induced apoptotic changes in renal tubular cells. Additionally, exposure to M + CA increased phosphorylation of mitogen-activated protein kinases (MAPKs) coincided with increased Bax level and decreased Bcl2 level, resulting in caspase-3 activation. In summary, oxidative stress and simultaneous MAPKs and mitochondrial/caspase activation may be related to renal tubular cell apoptosis caused by M + CA.
•M + CA caused functional and histopathological alteration in the kidneys.•M + CA increased lipid peroxidation and decreased antioxidant enzyme activities in the kidneys.•M + CA induced renal tubular cell apoptotic changes in the kidneys.•M + CA caused phosphorylation of mitogen-activated protein kinases (MAPKs).•M + CA increased Bax and decreased Bcl2 levels with caspase-3 activation in the kidneys.</description><subject>Animals</subject><subject>Antioxidants - metabolism</subject><subject>Apoptosis</subject><subject>Body Weight - drug effects</subject><subject>Cyanuric acid</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Combinations</subject><subject>Female</subject><subject>Glutathione - metabolism</subject><subject>Immunoblotting</subject><subject>Kidney Diseases - drug therapy</subject><subject>Kidney Diseases - etiology</subject><subject>Kidney Diseases - metabolism</subject><subject>Kidney Diseases - pathology</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Melamine</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Mitogen-activated protein kinases</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Nephrotoxicity</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Triazines - toxicity</subject><issn>0278-6915</issn><issn>1873-6351</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFP3DAQha0K1F1of0AvKEcuScdJ7TjqCSHaoi6CAz1bjj3ZepXYWztGXfHn8bLAkct4rPfeJ80j5AuFigLlXzfVoOeqzmsFogLafCBLKtqm5A2jR2QJdStK3lG2ICcxbgCgpS3_SBZ1y-qm7uolebzBUU3WYaGcKfROuRSsLpS2-edL_L_1MQUstEoRYxHQqbEwuzgkp2fr3XMsziHpOYW9pCa1xuLBquLm4u53fNYnO3v91zsTbLZEu84Q69afyPGgxoifX95T8ufH1f3lr3J1-_P68mJV6kbwuRxMz1rWd6AHjowbpFybPI1qGRWiYwp4DwywzyLtGK873oASDUPo8sHNKTk_cLfB_0sYZznZqHEclUOfoqSibjsK7BvNVnqw6uBjDDjIbbCTCjtJQe47lxuZO5f7ziUImTvPmbMXfOonNG-J15Kz4fvBgPnIB4tBRm3RaTQ2YIYZb9_BPwEsLZNi</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>Lee, In-Chul</creator><creator>Ko, Je-Won</creator><creator>Park, Sung-Hyeuk</creator><creator>Shin, In-Sik</creator><creator>Moon, Changjong</creator><creator>Kim, Sung-Ho</creator><creator>Kim, Yun-Bae</creator><creator>Kim, Jong-Choon</creator><general>Elsevier 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>7U7</scope><scope>C1K</scope><scope>SOI</scope></search><sort><creationdate>201610</creationdate><title>Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling</title><author>Lee, In-Chul ; Ko, Je-Won ; Park, Sung-Hyeuk ; Shin, In-Sik ; Moon, Changjong ; Kim, Sung-Ho ; Kim, Yun-Bae ; Kim, Jong-Choon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-fdb575b90cf6e56de16cdde1da7518895a06b050eb56d195629630a835e097173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antioxidants - metabolism</topic><topic>Apoptosis</topic><topic>Body Weight - drug effects</topic><topic>Cyanuric acid</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Combinations</topic><topic>Female</topic><topic>Glutathione - metabolism</topic><topic>Immunoblotting</topic><topic>Kidney Diseases - drug therapy</topic><topic>Kidney Diseases - etiology</topic><topic>Kidney Diseases - metabolism</topic><topic>Kidney Diseases - pathology</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Melamine</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Mitogen-activated protein kinases</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Nephrotoxicity</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Triazines - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, In-Chul</creatorcontrib><creatorcontrib>Ko, Je-Won</creatorcontrib><creatorcontrib>Park, Sung-Hyeuk</creatorcontrib><creatorcontrib>Shin, In-Sik</creatorcontrib><creatorcontrib>Moon, Changjong</creatorcontrib><creatorcontrib>Kim, Sung-Ho</creatorcontrib><creatorcontrib>Kim, Yun-Bae</creatorcontrib><creatorcontrib>Kim, Jong-Choon</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><jtitle>Food and chemical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, In-Chul</au><au>Ko, Je-Won</au><au>Park, Sung-Hyeuk</au><au>Shin, In-Sik</au><au>Moon, Changjong</au><au>Kim, Sung-Ho</au><au>Kim, Yun-Bae</au><au>Kim, Jong-Choon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling</atitle><jtitle>Food and chemical toxicology</jtitle><addtitle>Food Chem Toxicol</addtitle><date>2016-10</date><risdate>2016</risdate><volume>96</volume><spage>254</spage><epage>262</epage><pages>254-262</pages><issn>0278-6915</issn><eissn>1873-6351</eissn><abstract>Both melamine and cyanuric acid have low toxicity, but combined exposure to melamine and cyanuric acid (M + CA) was reported to cause unexpected toxicological synergy on kidney damage. In this study, we investigated the role of oxidative stress and apoptotic changes in the nephrotoxicity caused by M + CA in rats. M + CA treatment caused an increase in the kidney weight, serum blood urea nitrogen or creatinine levels in a dose-dependent manner. With severe morphological and histological changes in kidneys, M + CA markedly elevated lipid peroxidation and suppressed antioxidant enzyme activities. M + CA treatment induced apoptotic changes in renal tubular cells. Additionally, exposure to M + CA increased phosphorylation of mitogen-activated protein kinases (MAPKs) coincided with increased Bax level and decreased Bcl2 level, resulting in caspase-3 activation. In summary, oxidative stress and simultaneous MAPKs and mitochondrial/caspase activation may be related to renal tubular cell apoptosis caused by M + CA.
•M + CA caused functional and histopathological alteration in the kidneys.•M + CA increased lipid peroxidation and decreased antioxidant enzyme activities in the kidneys.•M + CA induced renal tubular cell apoptotic changes in the kidneys.•M + CA caused phosphorylation of mitogen-activated protein kinases (MAPKs).•M + CA increased Bax and decreased Bcl2 levels with caspase-3 activation in the kidneys.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27523292</pmid><doi>10.1016/j.fct.2016.08.013</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0278-6915 |
| ispartof | Food and chemical toxicology, 2016-10, Vol.96, p.254-262 |
| issn | 0278-6915 1873-6351 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1827910541 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Antioxidants - metabolism Apoptosis Body Weight - drug effects Cyanuric acid Dose-Response Relationship, Drug Drug Combinations Female Glutathione - metabolism Immunoblotting Kidney Diseases - drug therapy Kidney Diseases - etiology Kidney Diseases - metabolism Kidney Diseases - pathology Lipid Peroxidation - drug effects Melamine Mitochondria - drug effects Mitochondria - metabolism Mitogen-activated protein kinases Mitogen-Activated Protein Kinases - metabolism Nephrotoxicity Rats Rats, Sprague-Dawley Signal Transduction - drug effects Triazines - toxicity |
| title | Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T08%3A30%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Melamine%20and%20cyanuric%20acid%20co-exposure%20causes%20renal%20dysfunction%20and%20structural%20damage%20via%20MAPKs%20and%20mitochondrial%20signaling&rft.jtitle=Food%20and%20chemical%20toxicology&rft.au=Lee,%20In-Chul&rft.date=2016-10&rft.volume=96&rft.spage=254&rft.epage=262&rft.pages=254-262&rft.issn=0278-6915&rft.eissn=1873-6351&rft_id=info:doi/10.1016/j.fct.2016.08.013&rft_dat=%3Cproquest_cross%3E1827910541%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1827910541&rft_id=info:pmid/27523292&rft_els_id=S0278691516302794&rfr_iscdi=true |