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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2017-09, Vol.12 (9), p.e0183959-e0183959
Hauptverfasser: Yokota, Tsubasa, Omachi, Kohei, Suico, Mary Ann, Kojima, Haruka, Kamura, Misato, Teramoto, Keisuke, Kaseda, Shota, Kuwazuru, Jun, Shuto, Tsuyoshi, Kai, Hirofumi
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 &amp; 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 &amp; 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 &amp; 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 &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; 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 &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; 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 &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; 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 &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; 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