Effect of the combination of anti-inflammatory and antioxidant on dystrophic muscle cells

• Grant number: 13/17299-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2014
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Elaine Minatel
• Grantee: Aline Reis Fogaça
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Intense inflammatory process and oxidative stress are two process that contribute to the pathophysiology of dystrophic muscle fibers. Among the mechanisms involved in the inflammatory response in Duchenne muscular dystrophy (DMD) and mdx mice (an experimental model of DMD), stands out the signaling pathway of the factor of NF-kB, whose main route of action is the activation of cytokines pro-inflammatory such as tumor necrosis factor alpha (TNF-±) and interleukin IL-1².In addition the reactive oxygen species (ROS) have also been related to the activation of the NF-ºB factor in dystrophic muscle fibers. Based on the reasons above, in this project we hypothesized that the treatment with anti-inflammatory Diacerhein in combination with the antioxidant Vitamin E may produce a potential therapeutic effect on the muscle fibers of dystrophic mdx mice.Studies have shown that Diacerhein inhibits the synthesis and the activity of pro-inflammatory cytokines such as TNF-±, IL-6 and IL-1², while the Vitamin E efficiently prevents membrane lipid peroxidation. To verify the hypothesis, primary culture of muscle cells from mdx mice will be treated by the association of Diacerein and Vitamin E. Untreated mdx and muscle cells from C57BL/10 mice will be used as control. After the treatment, the muscle cells will be used for intracellular calcium analysis (Fluo-4 indicator), measurement of TNF-±, NF-kB and 4-HNE (Western blotting), and determination of the concentration of H2O2 (Amplex Red). The results will be statistically analyzed. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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. Beneficial cilostazol therapeutic effects in mdx dystrophic skeletal muscle. Clinical and Experimental Pharmacology and Physiology, v. 43, n. 2, p. 259-267, FEB 2016. (11/02474-4, 13/17299-9, 13/01294-8)

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. Beneficial cilostazol therapeutic effects in mdx dystrophic skeletal muscle. Clinical and experimental pharmacology & physiology, v. 43, n. 2, p. 9-pg., 2016-02-01. (11/02474-4, 13/17299-9, 13/01294-8)

MACEDO, ALINE BARBOSA; RAPUCCI MORAES, LUIS HENRIQUE; MIZOBUTI, DANIELA SAYURI; FOGACA, ALINE REIS; RAPUCCI MORAES, FERNANDA DOS SANTOS; HERMES, TULIO DE ALMEIDA; PERTILLE, ADRIANA; MINATEL, ELAINE. Low-Level Laser Therapy (LLLT) in Dystrophin-Deficient Muscle Cells: Effects on Regeneration Capacity, Inflammation Response and Oxidative Stress. PLoS One, v. 10, n. 6, JUN 17 2015. (11/02474-4, 13/17299-9, 10/01087-4)