title: Imatinib mesylate ameliorates the dystrophic phenotype in exercised mdx mice.
abstract: Myofiber degeneration, inflammation, and fibrosis are remarkable features of Duchenne muscular dystrophy. We hypothesized that the administration of imatinib mesylate, an inhibitor of tyrosine kinase and TGF-beta pro-fibrogenic activity, could improve the muscular conditions in mdx mice. Four-week old mdx mice were treated and exercised for 6 weeks. Gastrocnemius and diaphragm histopathology, strength, creatine kinase, and cytokine levels were evaluated. The treated group presented increased muscular strength and decreased CK levels, injured myofibers, and inflammatory infiltrates. Pro-inflammatory cytokines and TGF-beta were also reduced, while IL-10 was increased, suggesting an immunomodulatory effect of imatinib, which can ameliorate the dystrophic phenotype in mdx mice.
authors.affiliation: Muscular Dystrophy Research Center (AADM/UNAERP), School of Medicine, University of Ribeirão Preto, 14096-900 Ribeirão Preto-SP, Brazil. bizario@uol.com.br
authors.forename: João Carlos da Silva
authors.initials: JC
authors.lastname: Bizario
authors.forename: Daniel Giuliano
authors.initials: DG
authors.lastname: Cerri
authors.forename: Lilian Cataldi
authors.initials: LC
authors.lastname: Rodrigues
authors.forename: Gislane L V
authors.initials: GL
authors.lastname: Oliveira
authors.forename: Auro
authors.initials: A
authors.lastname: Nomizo
authors.forename: Daniela Dover
authors.initials: DD
authors.lastname: de Araujo
authors.forename: Paula Sakemi
authors.initials: PS
authors.lastname: Fukuhara
authors.forename: Juliana Caldas
authors.initials: JC
authors.lastname: Ribeiro
authors.forename: Fabíola Attié
authors.initials: FA
authors.lastname: de Castro
authors.forename: Maria Cristina Ramos
authors.initials: MC
authors.lastname: Costa
mesh_terms: D000818:Animals; D001549:Benzamides; D003402:Creatine Kinase / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D000068877:Imatinib Mesylate; D008297:Male; D051379:Mice; D009132:Muscles / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*; D010805:Physical Conditioning, Animal; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D003402:Creatine Kinase