Resveratrol decreases inflammation and increases utrophin gene expression in the mdx mouse model of Duchenne muscular dystrophy.
OBJECTIVE
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.
Department of Exercise Science, University of South Carolina, Columbia, SC 29208, USA.
Bradley S
BS
Gordon
Diana C
DC
Delgado Díaz
Matthew C
MC
Kostek
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015854:Up-Regulation; D049411:Utrophin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; C483600:Utrn protein, mouse; D049411:Utrophin; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol