Imatinib mesylate ameliorates the dystrophic phenotype in exercised mdx mice.
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.
Bizario
João Carlos da Silva
JC
Muscular Dystrophy Research Center (AADM/UNAERP), School of Medicine, University of Ribeirão Preto, 14096-900 Ribeirão Preto-SP, Brazil. bizario@uol.com.br
Cerri
Daniel Giuliano
DG
Rodrigues
Lilian Cataldi
LC
Oliveira
Gislane L V
GL
Nomizo
Auro
A
de Araujo
Daniela Dover
DD
Fukuhara
Paula Sakemi
PS
Ribeiro
Juliana Caldas
JC
de Castro
Fabíola Attié
FA
Costa
Maria Cristina Ramos
MC
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*
D001549:Benzamides; D016207:Cytokines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D003402:Creatine Kinase