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Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of duchenne muscular dystrophy
Summary Background & aims Duchenne muscular dystrophy (DMD) is a lethal genetic disease with no cure. Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identi...
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| Published in: | Clinical nutrition (Edinburgh, Scotland) Scotland), 2013-02, Vol.32 (1), p.104-111 |
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| creator | Gordon, Bradley S Delgado Díaz, Diana C Kostek, Matthew C |
| description | Summary Background & aims Duchenne muscular dystrophy (DMD) is a lethal genetic disease with no cure. Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identify an active dose of resveratrol in mdx mice and examine if this dose decreased inflammation and increased utrophin expression. Methods 5-week old mdx mice were given 0, 10, 100, or 500 mg/kg of resveratrol everyday for 10 days. Sirt1 was measured by qRT-PCR and used to determine the most active dose. Muscle inflammation was measured by H&E staining, CD45 and F4/80 immunohistochemistry. IL-6, TNFα, PGC-1α, and utrophin gene expression were measured by qRT-PCR. Utrophin, Sirt1, and PGC-1α protein were quantified by western blot. Results The 100 mg/kg dose of resveratrol, the most active dose, increased Sirt1 mRNA 60 ± 10% ( p |
| doi_str_mv | 10.1016/j.clnu.2012.06.003 |
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Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identify an active dose of resveratrol in mdx mice and examine if this dose decreased inflammation and increased utrophin expression. Methods 5-week old mdx mice were given 0, 10, 100, or 500 mg/kg of resveratrol everyday for 10 days. Sirt1 was measured by qRT-PCR and used to determine the most active dose. Muscle inflammation was measured by H&E staining, CD45 and F4/80 immunohistochemistry. IL-6, TNFα, PGC-1α, and utrophin gene expression were measured by qRT-PCR. Utrophin, Sirt1, and PGC-1α protein were quantified by western blot. Results The 100 mg/kg dose of resveratrol, the most active dose, increased Sirt1 mRNA 60 ± 10% ( p < 0.01), reduced immune cell infiltration 21 ± 6% (H&E) and 42 ± 8% (CD45 immunohistochemistry ( p < 0.05)), reduced macrophage infiltration 48 ± 10% (F4/80 immunohistochemistry ( p < 0.05)), and increased IL-6, PGC-1α, and utrophin mRNA 247 ± 77%, 27 ± 17%, and 43 ± 23% respectively ( p ≤ 0.05). Utrophin, Sirt1, and PGC-1α protein expression did not change. Conclusions Resveratrol may be a therapy for DMD by reducing inflammation.]]></description><identifier>ISSN: 0261-5614</identifier><identifier>EISSN: 1532-1983</identifier><identifier>DOI: 10.1016/j.clnu.2012.06.003</identifier><identifier>PMID: 22795790</identifier><identifier>CODEN: CLNUDP</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>animal models ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Biological and medical sciences ; Body Weight ; Dietary Supplements ; Disease Models, Animal ; Diseases of striated muscles. Neuromuscular diseases ; Feeding. Feeding behavior ; Fundamental and applied biological sciences. Psychology ; Gastroenterology and Hepatology ; gene expression ; immunohistochemistry ; Inflammation ; Inflammation Mediators - metabolism ; interleukin-6 ; Leukocytes - immunology ; Leukocytes - metabolism ; Leukocytes - pathology ; macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - pathology ; Male ; Medical sciences ; messenger RNA ; Mice ; Mice, Inbred mdx ; Muscle Development ; Muscle, Skeletal - immunology ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; muscles ; muscular dystrophy ; Muscular Dystrophy, Duchenne - diet therapy ; Muscular Dystrophy, Duchenne - immunology ; Muscular Dystrophy, Duchenne - metabolism ; Muscular Dystrophy, Duchenne - pathology ; Neurology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; PGC-1α ; protein synthesis ; Resveratrol ; reverse transcriptase polymerase chain reaction ; RNA, Messenger - metabolism ; Sirtuin 1 - biosynthesis ; Sirtuin 1 - genetics ; Sirtuin 1 - metabolism ; Stilbenes - administration & dosage ; Stilbenes - therapeutic use ; therapeutics ; Trans-Activators - biosynthesis ; Trans-Activators - genetics ; Trans-Activators - metabolism ; Transcription Factors ; tumor necrosis factor-alpha ; Up-Regulation ; Utrophin ; Utrophin - biosynthesis ; Utrophin - genetics ; Utrophin - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Western blotting</subject><ispartof>Clinical nutrition (Edinburgh, Scotland), 2013-02, Vol.32 (1), p.104-111</ispartof><rights>Elsevier Ltd and European Society for Clinical Nutrition and Metabolism</rights><rights>2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-2845b2a1c955a8cffedded1a3831b0309cb5500d29253113127d6cc56103191e3</citedby><cites>FETCH-LOGICAL-c465t-2845b2a1c955a8cffedded1a3831b0309cb5500d29253113127d6cc56103191e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26850901$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22795790$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gordon, Bradley S</creatorcontrib><creatorcontrib>Delgado Díaz, Diana C</creatorcontrib><creatorcontrib>Kostek, Matthew C</creatorcontrib><title>Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of duchenne muscular dystrophy</title><title>Clinical nutrition (Edinburgh, Scotland)</title><addtitle>Clin Nutr</addtitle><description><![CDATA[Summary Background & aims Duchenne muscular dystrophy (DMD) is a lethal genetic disease with no cure. Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identify an active dose of resveratrol in mdx mice and examine if this dose decreased inflammation and increased utrophin expression. Methods 5-week old mdx mice were given 0, 10, 100, or 500 mg/kg of resveratrol everyday for 10 days. Sirt1 was measured by qRT-PCR and used to determine the most active dose. Muscle inflammation was measured by H&E staining, CD45 and F4/80 immunohistochemistry. IL-6, TNFα, PGC-1α, and utrophin gene expression were measured by qRT-PCR. Utrophin, Sirt1, and PGC-1α protein were quantified by western blot. Results The 100 mg/kg dose of resveratrol, the most active dose, increased Sirt1 mRNA 60 ± 10% ( p < 0.01), reduced immune cell infiltration 21 ± 6% (H&E) and 42 ± 8% (CD45 immunohistochemistry ( p < 0.05)), reduced macrophage infiltration 48 ± 10% (F4/80 immunohistochemistry ( p < 0.05)), and increased IL-6, PGC-1α, and utrophin mRNA 247 ± 77%, 27 ± 17%, and 43 ± 23% respectively ( p ≤ 0.05). Utrophin, Sirt1, and PGC-1α protein expression did not change. Conclusions Resveratrol may be a therapy for DMD by reducing inflammation.]]></description><subject>animal models</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Dietary Supplements</subject><subject>Disease Models, Animal</subject><subject>Diseases of striated muscles. Neuromuscular diseases</subject><subject>Feeding. Feeding behavior</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology and Hepatology</subject><subject>gene expression</subject><subject>immunohistochemistry</subject><subject>Inflammation</subject><subject>Inflammation Mediators - metabolism</subject><subject>interleukin-6</subject><subject>Leukocytes - immunology</subject><subject>Leukocytes - metabolism</subject><subject>Leukocytes - pathology</subject><subject>macrophages</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred mdx</subject><subject>Muscle Development</subject><subject>Muscle, Skeletal - immunology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>muscles</subject><subject>muscular dystrophy</subject><subject>Muscular Dystrophy, Duchenne - diet therapy</subject><subject>Muscular Dystrophy, Duchenne - immunology</subject><subject>Muscular Dystrophy, Duchenne - metabolism</subject><subject>Muscular Dystrophy, Duchenne - pathology</subject><subject>Neurology</subject><subject>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</subject><subject>PGC-1α</subject><subject>protein synthesis</subject><subject>Resveratrol</subject><subject>reverse transcriptase polymerase chain reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Sirtuin 1 - biosynthesis</subject><subject>Sirtuin 1 - genetics</subject><subject>Sirtuin 1 - metabolism</subject><subject>Stilbenes - administration & dosage</subject><subject>Stilbenes - therapeutic use</subject><subject>therapeutics</subject><subject>Trans-Activators - biosynthesis</subject><subject>Trans-Activators - genetics</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factors</subject><subject>tumor necrosis factor-alpha</subject><subject>Up-Regulation</subject><subject>Utrophin</subject><subject>Utrophin - biosynthesis</subject><subject>Utrophin - genetics</subject><subject>Utrophin - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Western blotting</subject><issn>0261-5614</issn><issn>1532-1983</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kk9v1DAQxSMEotvCF-AAuSBxyTK2104soUqo4p9UCYnSs-W1J10vibPYSdU98dU7YbcgceBka_x7zzPPLooXDJYMmHq7XbouTksOjC9BLQHEo2LBpOAV0414XCyAK1ZJxVYnxWnOWwCQom6eFiec11rWGhbFr2-YbzHZMQ1d6dEltBlzGWLb2b63YxhiaaOnwsPRROhuE2J5gxFLvNslzHnGqDRusOz9XdkPU6bd4LErh7b0k9tgJLqfsps6m0q_z79t9s-KJ63tMj4_rmfF9ccP3y8-V5dfP325eH9ZuZWSY8WblVxzy5yW0jaubdF79MyKRrA1CNBuLSWA55pLwZhgvPbKOZodBNMMxVnx5uC7S8PPCfNo-pAddp2NSM0aEgilmdKSUH5AXRpyTtiaXQq9TXvDwMzBm62Zgzdz8AaUoeBJ9PLoP6179H8kD0kT8PoI2Oxs1yYbXch_OdVI0MCIe3XgWjsYe5OIub6im2g6qDXXNRHvDgRSXrcBk8kuYHToQ0I3Gj-E_3d6_o_cdSEG6ukH7jFvhylFegnDTCaNuZo_0fyHGAdyUStxD2x0wWo</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Gordon, Bradley S</creator><creator>Delgado Díaz, Diana C</creator><creator>Kostek, Matthew C</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of duchenne muscular dystrophy</title><author>Gordon, Bradley S ; Delgado Díaz, Diana C ; Kostek, Matthew C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-2845b2a1c955a8cffedded1a3831b0309cb5500d29253113127d6cc56103191e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>animal models</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Dietary Supplements</topic><topic>Disease Models, Animal</topic><topic>Diseases of striated muscles. Neuromuscular diseases</topic><topic>Feeding. Feeding behavior</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology and Hepatology</topic><topic>gene expression</topic><topic>immunohistochemistry</topic><topic>Inflammation</topic><topic>Inflammation Mediators - metabolism</topic><topic>interleukin-6</topic><topic>Leukocytes - immunology</topic><topic>Leukocytes - metabolism</topic><topic>Leukocytes - pathology</topic><topic>macrophages</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>messenger RNA</topic><topic>Mice</topic><topic>Mice, Inbred mdx</topic><topic>Muscle Development</topic><topic>Muscle, Skeletal - immunology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>muscles</topic><topic>muscular dystrophy</topic><topic>Muscular Dystrophy, Duchenne - diet therapy</topic><topic>Muscular Dystrophy, Duchenne - immunology</topic><topic>Muscular Dystrophy, Duchenne - metabolism</topic><topic>Muscular Dystrophy, Duchenne - pathology</topic><topic>Neurology</topic><topic>Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha</topic><topic>PGC-1α</topic><topic>protein synthesis</topic><topic>Resveratrol</topic><topic>reverse transcriptase polymerase chain reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Sirtuin 1 - biosynthesis</topic><topic>Sirtuin 1 - genetics</topic><topic>Sirtuin 1 - metabolism</topic><topic>Stilbenes - administration & dosage</topic><topic>Stilbenes - therapeutic use</topic><topic>therapeutics</topic><topic>Trans-Activators - biosynthesis</topic><topic>Trans-Activators - genetics</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription Factors</topic><topic>tumor necrosis factor-alpha</topic><topic>Up-Regulation</topic><topic>Utrophin</topic><topic>Utrophin - biosynthesis</topic><topic>Utrophin - genetics</topic><topic>Utrophin - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gordon, Bradley S</creatorcontrib><creatorcontrib>Delgado Díaz, Diana C</creatorcontrib><creatorcontrib>Kostek, Matthew C</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gordon, Bradley S</au><au>Delgado Díaz, Diana C</au><au>Kostek, Matthew C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of duchenne muscular dystrophy</atitle><jtitle>Clinical nutrition (Edinburgh, Scotland)</jtitle><addtitle>Clin Nutr</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>32</volume><issue>1</issue><spage>104</spage><epage>111</epage><pages>104-111</pages><issn>0261-5614</issn><eissn>1532-1983</eissn><coden>CLNUDP</coden><notes>http://dx.doi.org/10.1016/j.clnu.2012.06.003</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract><![CDATA[Summary Background & aims Duchenne muscular dystrophy (DMD) is a lethal genetic disease with no cure. Reducing inflammation or increasing utrophin expression can alleviate DMD pathology. Resveratrol can reduce inflammation and activate the utrophin promoter. The aims of this study were to identify an active dose of resveratrol in mdx mice and examine if this dose decreased inflammation and increased utrophin expression. Methods 5-week old mdx mice were given 0, 10, 100, or 500 mg/kg of resveratrol everyday for 10 days. Sirt1 was measured by qRT-PCR and used to determine the most active dose. Muscle inflammation was measured by H&E staining, CD45 and F4/80 immunohistochemistry. IL-6, TNFα, PGC-1α, and utrophin gene expression were measured by qRT-PCR. Utrophin, Sirt1, and PGC-1α protein were quantified by western blot. Results The 100 mg/kg dose of resveratrol, the most active dose, increased Sirt1 mRNA 60 ± 10% ( p < 0.01), reduced immune cell infiltration 21 ± 6% (H&E) and 42 ± 8% (CD45 immunohistochemistry ( p < 0.05)), reduced macrophage infiltration 48 ± 10% (F4/80 immunohistochemistry ( p < 0.05)), and increased IL-6, PGC-1α, and utrophin mRNA 247 ± 77%, 27 ± 17%, and 43 ± 23% respectively ( p ≤ 0.05). Utrophin, Sirt1, and PGC-1α protein expression did not change. Conclusions Resveratrol may be a therapy for DMD by reducing inflammation.]]></abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>22795790</pmid><doi>10.1016/j.clnu.2012.06.003</doi><tpages>8</tpages></addata></record> |
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| ispartof | Clinical nutrition (Edinburgh, Scotland), 2013-02, Vol.32 (1), p.104-111 |
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| subjects | animal models Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Biological and medical sciences Body Weight Dietary Supplements Disease Models, Animal Diseases of striated muscles. Neuromuscular diseases Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Gastroenterology and Hepatology gene expression immunohistochemistry Inflammation Inflammation Mediators - metabolism interleukin-6 Leukocytes - immunology Leukocytes - metabolism Leukocytes - pathology macrophages Macrophages - immunology Macrophages - metabolism Macrophages - pathology Male Medical sciences messenger RNA Mice Mice, Inbred mdx Muscle Development Muscle, Skeletal - immunology Muscle, Skeletal - metabolism Muscle, Skeletal - pathology muscles muscular dystrophy Muscular Dystrophy, Duchenne - diet therapy Muscular Dystrophy, Duchenne - immunology Muscular Dystrophy, Duchenne - metabolism Muscular Dystrophy, Duchenne - pathology Neurology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha PGC-1α protein synthesis Resveratrol reverse transcriptase polymerase chain reaction RNA, Messenger - metabolism Sirtuin 1 - biosynthesis Sirtuin 1 - genetics Sirtuin 1 - metabolism Stilbenes - administration & dosage Stilbenes - therapeutic use therapeutics Trans-Activators - biosynthesis Trans-Activators - genetics Trans-Activators - metabolism Transcription Factors tumor necrosis factor-alpha Up-Regulation Utrophin Utrophin - biosynthesis Utrophin - genetics Utrophin - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems Western blotting |
| title | Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of duchenne muscular dystrophy |
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