Beneficial cilostazol therapeutic effects in mdx dystrophic skeletal muscle

Author(s)

Hermes, Tulio de Almeida ; Macedo, Aline Barbosa ; Fogaca, Aline Reis ; Rapucci Moraes, Luis Henrique ; de Faria, Felipe Meira ; Kido, Larissa Akemi ; Alves Cagnon, Valeria Helena ; Minatel, Elaine

• Document type: Journal article
• Source: Clinical and experimental pharmacology & physiology; v. 43, n. 2, p. 9-pg., 2016-02-01.

Abstract

This study evaluated the possible protective effects of cilostazol against myonecrosis in dystrophic diaphragm muscle invivo, focusing on oxidative stress, the inflammatory response and angiogenesis. Young mdx mice, the experimental animal for Duchenne muscular dystrophy, received cilostazol for 14days. 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-B (-24%) and tumour necrosis factor- (-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. (AU)

• FAPESP's process: 11/02474-4 - Treatment in vivo and in vitro with calcium blocker and antioxidant in mdx mice
• Grantee: Elaine Minatel
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/17299-9 - Effect of the combination of anti-inflammatory and antioxidant on dystrophic muscle cells
• Grantee: Aline Reis Fogaça
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/01294-8 - The controversial relationship between inflammation and prostatic lesions: treatment with Celecoxib and Goniothalamin in senile and Tramp mice
• Grantee: Larissa Akemi Kido de Barros
• Support Opportunities: Scholarships in Brazil - Doctorate