Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome
A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic dr...
Gespeichert in:
Veröffentlicht in: | PloS one 2017-09, Vol.12 (9), p.e0183959-e0183959 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e0183959 |
---|---|
container_issue | 9 |
container_start_page | e0183959 |
container_title | PloS one |
container_volume | 12 |
creator | Yokota, Tsubasa Omachi, Kohei Suico, Mary Ann Kojima, Haruka Kamura, Misato Teramoto, Keisuke Kaseda, Shota Kuwazuru, Jun Shuto, Tsuyoshi Kai, Hirofumi |
description | A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS. |
doi_str_mv | 10.1371/journal.pone.0183959 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1935878114</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A503304438</galeid><doaj_id>oai_doaj_org_article_3ae93002d9c9477bb7d49f7bdfe95c79</doaj_id><sourcerecordid>A503304438</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-54d2109abf1f85194b41fb9d794ac09af0ffa39bbf5a4488d315eeeb726baec53</originalsourceid><addsrcrecordid>eNqNk2uL1DAUhosorq7-A9GAIArOmDRJm3wR1sXLwsKCt68hl5OZDG0zJq3s_HtTd3bZkf0ghTacPOc9zZtzquoZwUtCW_JuE6c06G65jQMsMRFUcnmvekQkrRdNjen9W-uj6nHOG4w5FU3zsDqqhWgp4_hRlT6k2AcHKE_bbQc9DKMeQxwQXGoLyegRHBrXgBKUYsjtsp8GOxNvURg2U9ohPTjkg0kxh1xiSKM-ThnK20GHokcn3TamEeXd4EoxeFI98LrL8HT_Pa5-fPr4_fTL4vzi89npyfnCtlyMC85cTbDUxhMvOJHMMOKNdK1k2pa4x95rKo3xXDMmhKOEA4Bp68ZosJweVy-udLddzGpvV1bFFC5aQQgrxNkV4aLeqG0KvU47FXVQfwMxrZROY7AdKKpBUoxrJ61kbWtM65j0rXEeJLetLFrv99Um04OzxcikuwPRw50hrNUq_lacCyabWeD1XiDFXxPkUfUhW-g6PUDxc_7vpm4IF3VBX_6D3n26PbXS5QBh8LHUtbOoOuGYUswYFYVa3kGVx0EfbOktH0r8IOHNQUJhRrgcV3rKWZ19-_r_7MXPQ_bVLXYNuhvXOXbT3Gv5EGRXoC0tlxP4G5MJVvNoXLuh5tFQ-9Eoac9vX9BN0vUs0D_i4wt-</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1935878114</pqid></control><display><type>article</type><title>Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Yokota, Tsubasa ; Omachi, Kohei ; Suico, Mary Ann ; Kojima, Haruka ; Kamura, Misato ; Teramoto, Keisuke ; Kaseda, Shota ; Kuwazuru, Jun ; Shuto, Tsuyoshi ; Kai, Hirofumi</creator><contributor>Datta, Prasun K.</contributor><creatorcontrib>Yokota, Tsubasa ; Omachi, Kohei ; Suico, Mary Ann ; Kojima, Haruka ; Kamura, Misato ; Teramoto, Keisuke ; Kaseda, Shota ; Kuwazuru, Jun ; Shuto, Tsuyoshi ; Kai, Hirofumi ; Datta, Prasun K.</creatorcontrib><description>A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0183959</identifier><identifier>PMID: 28873450</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alport syndrome ; Analysis ; Animals ; Antiepileptic agents ; Biology and Life Sciences ; Blood Urea Nitrogen ; Bromides - adverse effects ; Bromides - pharmacology ; Care and treatment ; Collagen ; Collagen (type I) ; Collagen (type IV) ; Creatinine ; Creatinine - blood ; Cytokines ; Development and progression ; Disease Models, Animal ; Diseases ; Dosage ; Drinking water ; Drug dosages ; Drugs ; Fibrosis ; Glomerular Basement Membrane - pathology ; Health aspects ; Hereditary nephritis ; Inflammation ; Injuries ; Injury analysis ; Insects ; Interdisciplinary aspects ; Interleukin 1 ; Interleukin 6 ; Interleukin 8 ; Kidney - metabolism ; Kidney diseases ; Kidney Diseases - metabolism ; Laboratories ; Life sciences ; Liver Cirrhosis ; Lysozyme ; Male ; Matrix metalloproteinase ; Medicine ; Medicine and Health Sciences ; Metabolism ; Metalloproteinase ; Mice ; Mice, Inbred C57BL ; Nephritis - pathology ; Nephritis, Hereditary - metabolism ; Nephrology ; Nitrogen - blood ; Pharmaceutical sciences ; Potassium ; Potassium Compounds - adverse effects ; Potassium Compounds - pharmacology ; Proteinuria ; Proteinuria - metabolism ; Renal function ; Research and Analysis Methods ; Risk factors ; Rodents ; Salts ; Side effects ; Sodium chloride ; Sodium Compounds - adverse effects ; Sodium Compounds - pharmacology ; Supplements ; Trace elements ; Transforming growth factors ; Transplants & implants ; Tumor necrosis factor ; Urea</subject><ispartof>PloS one, 2017-09, Vol.12 (9), p.e0183959-e0183959</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Yokota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Yokota et al 2017 Yokota et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-54d2109abf1f85194b41fb9d794ac09af0ffa39bbf5a4488d315eeeb726baec53</citedby><cites>FETCH-LOGICAL-c758t-54d2109abf1f85194b41fb9d794ac09af0ffa39bbf5a4488d315eeeb726baec53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584969/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584969/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28873450$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Datta, Prasun K.</contributor><creatorcontrib>Yokota, Tsubasa</creatorcontrib><creatorcontrib>Omachi, Kohei</creatorcontrib><creatorcontrib>Suico, Mary Ann</creatorcontrib><creatorcontrib>Kojima, Haruka</creatorcontrib><creatorcontrib>Kamura, Misato</creatorcontrib><creatorcontrib>Teramoto, Keisuke</creatorcontrib><creatorcontrib>Kaseda, Shota</creatorcontrib><creatorcontrib>Kuwazuru, Jun</creatorcontrib><creatorcontrib>Shuto, Tsuyoshi</creatorcontrib><creatorcontrib>Kai, Hirofumi</creatorcontrib><title>Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.</description><subject>Alport syndrome</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antiepileptic agents</subject><subject>Biology and Life Sciences</subject><subject>Blood Urea Nitrogen</subject><subject>Bromides - adverse effects</subject><subject>Bromides - pharmacology</subject><subject>Care and treatment</subject><subject>Collagen</subject><subject>Collagen (type I)</subject><subject>Collagen (type IV)</subject><subject>Creatinine</subject><subject>Creatinine - blood</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Disease Models, Animal</subject><subject>Diseases</subject><subject>Dosage</subject><subject>Drinking water</subject><subject>Drug dosages</subject><subject>Drugs</subject><subject>Fibrosis</subject><subject>Glomerular Basement Membrane - pathology</subject><subject>Health aspects</subject><subject>Hereditary nephritis</subject><subject>Inflammation</subject><subject>Injuries</subject><subject>Injury analysis</subject><subject>Insects</subject><subject>Interdisciplinary aspects</subject><subject>Interleukin 1</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Kidney - metabolism</subject><subject>Kidney diseases</subject><subject>Kidney Diseases - metabolism</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>Liver Cirrhosis</subject><subject>Lysozyme</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Metalloproteinase</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nephritis - pathology</subject><subject>Nephritis, Hereditary - metabolism</subject><subject>Nephrology</subject><subject>Nitrogen - blood</subject><subject>Pharmaceutical sciences</subject><subject>Potassium</subject><subject>Potassium Compounds - adverse effects</subject><subject>Potassium Compounds - pharmacology</subject><subject>Proteinuria</subject><subject>Proteinuria - metabolism</subject><subject>Renal function</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Salts</subject><subject>Side effects</subject><subject>Sodium chloride</subject><subject>Sodium Compounds - adverse effects</subject><subject>Sodium Compounds - pharmacology</subject><subject>Supplements</subject><subject>Trace elements</subject><subject>Transforming growth factors</subject><subject>Transplants & implants</subject><subject>Tumor necrosis factor</subject><subject>Urea</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk2uL1DAUhosorq7-A9GAIArOmDRJm3wR1sXLwsKCt68hl5OZDG0zJq3s_HtTd3bZkf0ghTacPOc9zZtzquoZwUtCW_JuE6c06G65jQMsMRFUcnmvekQkrRdNjen9W-uj6nHOG4w5FU3zsDqqhWgp4_hRlT6k2AcHKE_bbQc9DKMeQxwQXGoLyegRHBrXgBKUYsjtsp8GOxNvURg2U9ohPTjkg0kxh1xiSKM-ThnK20GHokcn3TamEeXd4EoxeFI98LrL8HT_Pa5-fPr4_fTL4vzi89npyfnCtlyMC85cTbDUxhMvOJHMMOKNdK1k2pa4x95rKo3xXDMmhKOEA4Bp68ZosJweVy-udLddzGpvV1bFFC5aQQgrxNkV4aLeqG0KvU47FXVQfwMxrZROY7AdKKpBUoxrJ61kbWtM65j0rXEeJLetLFrv99Um04OzxcikuwPRw50hrNUq_lacCyabWeD1XiDFXxPkUfUhW-g6PUDxc_7vpm4IF3VBX_6D3n26PbXS5QBh8LHUtbOoOuGYUswYFYVa3kGVx0EfbOktH0r8IOHNQUJhRrgcV3rKWZ19-_r_7MXPQ_bVLXYNuhvXOXbT3Gv5EGRXoC0tlxP4G5MJVvNoXLuh5tFQ-9Eoac9vX9BN0vUs0D_i4wt-</recordid><startdate>20170905</startdate><enddate>20170905</enddate><creator>Yokota, Tsubasa</creator><creator>Omachi, Kohei</creator><creator>Suico, Mary Ann</creator><creator>Kojima, Haruka</creator><creator>Kamura, Misato</creator><creator>Teramoto, Keisuke</creator><creator>Kaseda, Shota</creator><creator>Kuwazuru, Jun</creator><creator>Shuto, Tsuyoshi</creator><creator>Kai, Hirofumi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20170905</creationdate><title>Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome</title><author>Yokota, Tsubasa ; Omachi, Kohei ; Suico, Mary Ann ; Kojima, Haruka ; Kamura, Misato ; Teramoto, Keisuke ; Kaseda, Shota ; Kuwazuru, Jun ; Shuto, Tsuyoshi ; Kai, Hirofumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-54d2109abf1f85194b41fb9d794ac09af0ffa39bbf5a4488d315eeeb726baec53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Alport syndrome</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antiepileptic agents</topic><topic>Biology and Life Sciences</topic><topic>Blood Urea Nitrogen</topic><topic>Bromides - adverse effects</topic><topic>Bromides - pharmacology</topic><topic>Care and treatment</topic><topic>Collagen</topic><topic>Collagen (type I)</topic><topic>Collagen (type IV)</topic><topic>Creatinine</topic><topic>Creatinine - blood</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Disease Models, Animal</topic><topic>Diseases</topic><topic>Dosage</topic><topic>Drinking water</topic><topic>Drug dosages</topic><topic>Drugs</topic><topic>Fibrosis</topic><topic>Glomerular Basement Membrane - pathology</topic><topic>Health aspects</topic><topic>Hereditary nephritis</topic><topic>Inflammation</topic><topic>Injuries</topic><topic>Injury analysis</topic><topic>Insects</topic><topic>Interdisciplinary aspects</topic><topic>Interleukin 1</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Kidney - metabolism</topic><topic>Kidney diseases</topic><topic>Kidney Diseases - metabolism</topic><topic>Laboratories</topic><topic>Life sciences</topic><topic>Liver Cirrhosis</topic><topic>Lysozyme</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Metalloproteinase</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nephritis - pathology</topic><topic>Nephritis, Hereditary - metabolism</topic><topic>Nephrology</topic><topic>Nitrogen - blood</topic><topic>Pharmaceutical sciences</topic><topic>Potassium</topic><topic>Potassium Compounds - adverse effects</topic><topic>Potassium Compounds - pharmacology</topic><topic>Proteinuria</topic><topic>Proteinuria - metabolism</topic><topic>Renal function</topic><topic>Research and Analysis Methods</topic><topic>Risk factors</topic><topic>Rodents</topic><topic>Salts</topic><topic>Side effects</topic><topic>Sodium chloride</topic><topic>Sodium Compounds - adverse effects</topic><topic>Sodium Compounds - pharmacology</topic><topic>Supplements</topic><topic>Trace elements</topic><topic>Transforming growth factors</topic><topic>Transplants & implants</topic><topic>Tumor necrosis factor</topic><topic>Urea</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yokota, Tsubasa</creatorcontrib><creatorcontrib>Omachi, Kohei</creatorcontrib><creatorcontrib>Suico, Mary Ann</creatorcontrib><creatorcontrib>Kojima, Haruka</creatorcontrib><creatorcontrib>Kamura, Misato</creatorcontrib><creatorcontrib>Teramoto, Keisuke</creatorcontrib><creatorcontrib>Kaseda, Shota</creatorcontrib><creatorcontrib>Kuwazuru, Jun</creatorcontrib><creatorcontrib>Shuto, Tsuyoshi</creatorcontrib><creatorcontrib>Kai, Hirofumi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yokota, Tsubasa</au><au>Omachi, Kohei</au><au>Suico, Mary Ann</au><au>Kojima, Haruka</au><au>Kamura, Misato</au><au>Teramoto, Keisuke</au><au>Kaseda, Shota</au><au>Kuwazuru, Jun</au><au>Shuto, Tsuyoshi</au><au>Kai, Hirofumi</au><au>Datta, Prasun K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-09-05</date><risdate>2017</risdate><volume>12</volume><issue>9</issue><spage>e0183959</spage><epage>e0183959</epage><pages>e0183959-e0183959</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28873450</pmid><doi>10.1371/journal.pone.0183959</doi><tpages>e0183959</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2017-09, Vol.12 (9), p.e0183959-e0183959 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1935878114 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Alport syndrome Analysis Animals Antiepileptic agents Biology and Life Sciences Blood Urea Nitrogen Bromides - adverse effects Bromides - pharmacology Care and treatment Collagen Collagen (type I) Collagen (type IV) Creatinine Creatinine - blood Cytokines Development and progression Disease Models, Animal Diseases Dosage Drinking water Drug dosages Drugs Fibrosis Glomerular Basement Membrane - pathology Health aspects Hereditary nephritis Inflammation Injuries Injury analysis Insects Interdisciplinary aspects Interleukin 1 Interleukin 6 Interleukin 8 Kidney - metabolism Kidney diseases Kidney Diseases - metabolism Laboratories Life sciences Liver Cirrhosis Lysozyme Male Matrix metalloproteinase Medicine Medicine and Health Sciences Metabolism Metalloproteinase Mice Mice, Inbred C57BL Nephritis - pathology Nephritis, Hereditary - metabolism Nephrology Nitrogen - blood Pharmaceutical sciences Potassium Potassium Compounds - adverse effects Potassium Compounds - pharmacology Proteinuria Proteinuria - metabolism Renal function Research and Analysis Methods Risk factors Rodents Salts Side effects Sodium chloride Sodium Compounds - adverse effects Sodium Compounds - pharmacology Supplements Trace elements Transforming growth factors Transplants & implants Tumor necrosis factor Urea |
title | Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T01%3A55%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bromide%20supplementation%20exacerbated%20the%20renal%20dysfunction,%20injury%20and%20fibrosis%20in%20a%20mouse%20model%20of%20Alport%20syndrome&rft.jtitle=PloS%20one&rft.au=Yokota,%20Tsubasa&rft.date=2017-09-05&rft.volume=12&rft.issue=9&rft.spage=e0183959&rft.epage=e0183959&rft.pages=e0183959-e0183959&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0183959&rft_dat=%3Cgale_plos_%3EA503304438%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1935878114&rft_id=info:pmid/28873450&rft_galeid=A503304438&rft_doaj_id=oai_doaj_org_article_3ae93002d9c9477bb7d49f7bdfe95c79&rfr_iscdi=true |