Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice
ABSTRACT In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short‐t...
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Veröffentlicht in: | Anatomical record (Hoboken, N.J. : 2007) N.J. : 2007), 2015-09, Vol.298 (9), p.1589-1596 |
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creator | Apolinário, Leticia Montanholi De Carvalho, Samara Camaçari Santo Neto, Humberto Marques, Maria Julia |
description | ABSTRACT
In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short‐term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long‐term therapy with omega‐3 later in dystrophy progression. Three‐month‐old mdx mice received omega‐3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long‐term therapy with omega‐3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF‐α and NF‐kB) in both muscles studied. The present study supports the long‐term use of omega‐3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. Anat Rec, 298:1589–1596, 2015. © 2015 Wiley Periodicals, Inc. |
doi_str_mv | 10.1002/ar.23177 |
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In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short‐term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long‐term therapy with omega‐3 later in dystrophy progression. Three‐month‐old mdx mice received omega‐3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long‐term therapy with omega‐3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF‐α and NF‐kB) in both muscles studied. The present study supports the long‐term use of omega‐3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. Anat Rec, 298:1589–1596, 2015. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 1932-8486</identifier><identifier>EISSN: 1932-8494</identifier><identifier>DOI: 10.1002/ar.23177</identifier><identifier>PMID: 26011009</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; Diaphragm - drug effects ; Diaphragm - metabolism ; Diaphragm - pathology ; Diaphragm - physiopathology ; Disease Models, Animal ; DMD ; Docosahexaenoic Acids - administration & dosage ; Drug Administration Schedule ; dystrophy ; Eicosapentaenoic Acid - administration & dosage ; Female ; Inflammation Mediators - metabolism ; Male ; Mice, Inbred mdx ; Muscular Dystrophy, Animal - drug therapy ; Muscular Dystrophy, Animal - metabolism ; Muscular Dystrophy, Animal - pathology ; Muscular Dystrophy, Animal - physiopathology ; Muscular Dystrophy, Duchenne - drug therapy ; Muscular Dystrophy, Duchenne - metabolism ; Muscular Dystrophy, Duchenne - pathology ; Muscular Dystrophy, Duchenne - physiopathology ; MyoD Protein - metabolism ; Necrosis ; NF-kappa B - metabolism ; NF‐kB ; omega‐3 ; quadriceps ; Quadriceps Muscle - drug effects ; Quadriceps Muscle - metabolism ; Quadriceps Muscle - pathology ; Quadriceps Muscle - physiopathology ; Regeneration - drug effects ; Time Factors ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Anatomical record (Hoboken, N.J. : 2007), 2015-09, Vol.298 (9), p.1589-1596</ispartof><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4537-2efb38cf20664816f143ede4e5a880f7587f71b17845e1a9cf1b8483c2c031a03</citedby><cites>FETCH-LOGICAL-c4537-2efb38cf20664816f143ede4e5a880f7587f71b17845e1a9cf1b8483c2c031a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Far.23177$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Far.23177$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26011009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Apolinário, Leticia Montanholi</creatorcontrib><creatorcontrib>De Carvalho, Samara Camaçari</creatorcontrib><creatorcontrib>Santo Neto, Humberto</creatorcontrib><creatorcontrib>Marques, Maria Julia</creatorcontrib><title>Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice</title><title>Anatomical record (Hoboken, N.J. : 2007)</title><addtitle>Anat Rec (Hoboken)</addtitle><description>ABSTRACT
In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short‐term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long‐term therapy with omega‐3 later in dystrophy progression. Three‐month‐old mdx mice received omega‐3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long‐term therapy with omega‐3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF‐α and NF‐kB) in both muscles studied. The present study supports the long‐term use of omega‐3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. Anat Rec, 298:1589–1596, 2015. © 2015 Wiley Periodicals, Inc.</description><subject>Animals</subject><subject>Diaphragm - drug effects</subject><subject>Diaphragm - metabolism</subject><subject>Diaphragm - pathology</subject><subject>Diaphragm - physiopathology</subject><subject>Disease Models, Animal</subject><subject>DMD</subject><subject>Docosahexaenoic Acids - administration & dosage</subject><subject>Drug Administration Schedule</subject><subject>dystrophy</subject><subject>Eicosapentaenoic Acid - administration & dosage</subject><subject>Female</subject><subject>Inflammation Mediators - metabolism</subject><subject>Male</subject><subject>Mice, Inbred mdx</subject><subject>Muscular Dystrophy, Animal - drug therapy</subject><subject>Muscular Dystrophy, Animal - metabolism</subject><subject>Muscular Dystrophy, Animal - pathology</subject><subject>Muscular Dystrophy, Animal - physiopathology</subject><subject>Muscular Dystrophy, Duchenne - drug therapy</subject><subject>Muscular Dystrophy, Duchenne - metabolism</subject><subject>Muscular Dystrophy, Duchenne - pathology</subject><subject>Muscular Dystrophy, Duchenne - physiopathology</subject><subject>MyoD Protein - metabolism</subject><subject>Necrosis</subject><subject>NF-kappa B - metabolism</subject><subject>NF‐kB</subject><subject>omega‐3</subject><subject>quadriceps</subject><subject>Quadriceps Muscle - drug effects</subject><subject>Quadriceps Muscle - metabolism</subject><subject>Quadriceps Muscle - pathology</subject><subject>Quadriceps Muscle - physiopathology</subject><subject>Regeneration - drug effects</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>1932-8486</issn><issn>1932-8494</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKw0AUQAdRfFTBL5ABN26i80omWdbiCxoKWnEZJtM7dTSPOpOg3fkJfqNfYmprBcHVvXDPPdwHQoeUnFJC2Jlyp4xTKTfQLk04C2KRiM11Hkc7aM_7J0JCQRK-jXZYRGjXmOyi2bCupp_vH2NwJR4_glOzOX6wzSMelTBVXYXjfgmFrZ1qwON0XlegXe2tx6qa4HOowNjG47tnKKBRBU5brwvAtzDtSl2TrStsK5xO3nBqNeyjLaMKDwer2EP3lxfjwXUwHF3dDPrDQIuQy4CByXmsDSNRJGIaGSo4TEBAqOKYGBnG0kiaUxmLEKhKtKF5tynXTBNOFeE9dLL0zlz90oJvstJ6DUWhKqhbn1FJuCQRFwv0-A_6VLeu6qb7piiLWJj8ChfbewcmmzlbKjfPKMkWX8iUy76_0KFHK2GblzBZgz9n74BgCbzaAub_irL-7VL4Bdm1kGI</recordid><startdate>201509</startdate><enddate>201509</enddate><creator>Apolinário, Leticia Montanholi</creator><creator>De Carvalho, Samara Camaçari</creator><creator>Santo Neto, Humberto</creator><creator>Marques, Maria Julia</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TS</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201509</creationdate><title>Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice</title><author>Apolinário, Leticia Montanholi ; De Carvalho, Samara Camaçari ; Santo Neto, Humberto ; Marques, Maria Julia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4537-2efb38cf20664816f143ede4e5a880f7587f71b17845e1a9cf1b8483c2c031a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Diaphragm - drug effects</topic><topic>Diaphragm - metabolism</topic><topic>Diaphragm - pathology</topic><topic>Diaphragm - physiopathology</topic><topic>Disease Models, Animal</topic><topic>DMD</topic><topic>Docosahexaenoic Acids - administration & dosage</topic><topic>Drug Administration Schedule</topic><topic>dystrophy</topic><topic>Eicosapentaenoic Acid - administration & dosage</topic><topic>Female</topic><topic>Inflammation Mediators - metabolism</topic><topic>Male</topic><topic>Mice, Inbred mdx</topic><topic>Muscular Dystrophy, Animal - drug therapy</topic><topic>Muscular Dystrophy, Animal - metabolism</topic><topic>Muscular Dystrophy, Animal - pathology</topic><topic>Muscular Dystrophy, Animal - physiopathology</topic><topic>Muscular Dystrophy, Duchenne - drug therapy</topic><topic>Muscular Dystrophy, Duchenne - metabolism</topic><topic>Muscular Dystrophy, Duchenne - pathology</topic><topic>Muscular Dystrophy, Duchenne - physiopathology</topic><topic>MyoD Protein - metabolism</topic><topic>Necrosis</topic><topic>NF-kappa B - metabolism</topic><topic>NF‐kB</topic><topic>omega‐3</topic><topic>quadriceps</topic><topic>Quadriceps Muscle - drug effects</topic><topic>Quadriceps Muscle - metabolism</topic><topic>Quadriceps Muscle - pathology</topic><topic>Quadriceps Muscle - physiopathology</topic><topic>Regeneration - drug effects</topic><topic>Time Factors</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Apolinário, Leticia Montanholi</creatorcontrib><creatorcontrib>De Carvalho, Samara Camaçari</creatorcontrib><creatorcontrib>Santo Neto, Humberto</creatorcontrib><creatorcontrib>Marques, Maria Julia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Anatomical record (Hoboken, N.J. : 2007)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Apolinário, Leticia Montanholi</au><au>De Carvalho, Samara Camaçari</au><au>Santo Neto, Humberto</au><au>Marques, Maria Julia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice</atitle><jtitle>Anatomical record (Hoboken, N.J. : 2007)</jtitle><addtitle>Anat Rec (Hoboken)</addtitle><date>2015-09</date><risdate>2015</risdate><volume>298</volume><issue>9</issue><spage>1589</spage><epage>1596</epage><pages>1589-1596</pages><issn>1932-8486</issn><eissn>1932-8494</eissn><abstract>ABSTRACT
In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short‐term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long‐term therapy with omega‐3 later in dystrophy progression. Three‐month‐old mdx mice received omega‐3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long‐term therapy with omega‐3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF‐α and NF‐kB) in both muscles studied. The present study supports the long‐term use of omega‐3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. Anat Rec, 298:1589–1596, 2015. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26011009</pmid><doi>10.1002/ar.23177</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Diaphragm - drug effects Diaphragm - metabolism Diaphragm - pathology Diaphragm - physiopathology Disease Models, Animal DMD Docosahexaenoic Acids - administration & dosage Drug Administration Schedule dystrophy Eicosapentaenoic Acid - administration & dosage Female Inflammation Mediators - metabolism Male Mice, Inbred mdx Muscular Dystrophy, Animal - drug therapy Muscular Dystrophy, Animal - metabolism Muscular Dystrophy, Animal - pathology Muscular Dystrophy, Animal - physiopathology Muscular Dystrophy, Duchenne - drug therapy Muscular Dystrophy, Duchenne - metabolism Muscular Dystrophy, Duchenne - pathology Muscular Dystrophy, Duchenne - physiopathology MyoD Protein - metabolism Necrosis NF-kappa B - metabolism NF‐kB omega‐3 quadriceps Quadriceps Muscle - drug effects Quadriceps Muscle - metabolism Quadriceps Muscle - pathology Quadriceps Muscle - physiopathology Regeneration - drug effects Time Factors Tumor Necrosis Factor-alpha - metabolism |
title | Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice |
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