title: Beneficial cilostazol therapeutic effects in mdx dystrophic skeletal muscle.
abstract: This study evaluated the possible protective effects of cilostazol against myonecrosis in dystrophic diaphragm muscle in vivo, focusing on oxidative stress, the inflammatory response and angiogenesis. Young mdx mice, the experimental animal for Duchenne muscular dystrophy, received cilostazol for 14 days. A second group of mdx mice and a control group of C57BL/10 mice received a saline solution. In the mdx mice, cilostazol treatment was associated with reduced loss of muscle strength (-34.4%), decreased myonecrosis, reduced creatine kinase levels (-63.3%) and muscle fibres stained for immunoglobulin G in dystrophic diaphragm muscle (-81.1%), and a reduced inflammatory response, with a decreased inflammatory area (-22%), macrophage infiltration (-44.9%) and nuclear factor-κB (-24%) and tumour necrosis factor-α (-48%) content in dystrophic diaphragm muscle. Furthermore, cilostazol decreased oxidative stress and attenuated reactive oxygen species production (-74%) and lipid peroxidation (-17%) in dystrophic diaphragm muscle, and promoted the up-regulation of angiogenesis, increasing the number of microvessels (15%). In conclusion, the present results show that cilostazol has beneficial effects in dystrophic muscle. More research into the potential of cilostazol as a novel therapeutic agent for the treatment of dystrophinopathies is required.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Túlio de Almeida
authors.initials: Tde A
authors.lastname: Hermes
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Aline Barbosa
authors.initials: AB
authors.lastname: Macedo
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Aline Reis
authors.initials: AR
authors.lastname: Fogaça
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Luis Henrique Rapucci
authors.initials: LH
authors.lastname: Moraes
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Felipe Meira
authors.initials: FM
authors.lastname: de Faria
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Larissa Akemi
authors.initials: LA
authors.lastname: Kido
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Valéria Helena Alves
authors.initials: VH
authors.lastname: Cagnon
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Minatel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003402:Creatine Kinase / Q000097:blood; D003964:Diaphragm / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D013777:Tetrazoles; D003402:Creatine Kinase; D000077407:Cilostazol
keywords: angiogenesis; antioxidant; inflammation; muscular dystrophy