TEMPOL: POTENTIAL ANTIOXIDANT THERAPY FOR DYSTROPHIC MUSCULAR FIBERS

• Grant number: 17/01638-0
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2017 - October 31, 2019
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Elaine Minatel
• Grantee: Elaine Minatel
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Renato Ferretti ; Valéria Helena Alves Cagnon Quitete

Abstract

Oxidative stress has been considered a major factor in the physiopathogenesis of muscular dystrophies, especially in Duchenne muscular dystrophy (DMD). Despite the high concentration of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione, observed in dystrophic patients and mdx mice, the antioxidant system can not restore the body's balance. In view of the above, we hypothesized that treatment with Tempol, a SOD mimetic and also acting in a similar way to catalase, could have a potential effect on dystrophic muscle fibers. Thus, the present work aims to verify the potential antioxidant effect of Tempol in vitro and in vivo on the dystrophic muscle fibers of mdx mice. Primary cultures of muscle cells from mdx (DMD experimental model) and C57BL / 10 (control) mice will be used for the in vitro studies. Mdx cells will be treated with Tempol, untreated mdx cells and C57BL / 10 cells will be used as control. After treatment, the muscle cells will be used to determine cell viability, oxidative stress, enzymatic antioxidant system and inflammatory indicators. For in vivo studies, mdx mice with 14 days postnatal life will be divided into 3 experimental groups: saline, prednisolone and tempol. Mice of the C57BL / 10 strain will be used as controls and will not receive any type of treatment. Assessment of muscle strength will be performed before and after treatment. After the treatment, the diaphragm muscle (DIA) of the experimental groups will be removed and used to evaluate the degeneration / regeneration process, oxidative stress, enzymatic antioxidant system and inflammatory process through morphological, biochemical, Western blotting and extraction of Total RNA, reverse transcription and real time-PCR. The results will be submitted to statistical analysis through the ANOVA One Way test followed by the Tukey test. (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; MANCIO, RAFAEL DIAS; MACEDO, ALINE BARBOSA; MIZOBUTI, DANIELA SAYURI; DA ROCHA, GUILHERME LUIZ; ALVES CAGNON, VALERIA HELENA; MINATEL, ELAINE. Tempol treatment shows phenotype improvement in mdx mice. PLoS One, v. 14, n. 4, APR 22 2019. (14/01970-6, 17/01638-0)

SILVA, HELOINA NATHALLIE MARIANO DA; COVATTI, CAROLINE; ROCHA, GUILHERME LUIZ DA; MIZOBUTI, DANIELA SAYURI; MANCIO, RAFAEL DIAS; HERMES, TULIO DE ALMEIDA; KIDO, LARISSA AKEMI; CAGNON, VALERIA HELENA ALVES; PEREIRA, ELAINE CRISTINA LEITE; MINATEL, ELAINE. Oxidative Stress, Inflammation, and Activators of Mitochondrial Biogenesis: Tempol Targets in the Diaphragm Muscle of Exercise Trained-mdx Mice. FRONTIERS IN PHYSIOLOGY, v. 12, APR 26 2021. (17/01638-0)

HERMES, TULIO DE ALMEIDA; MIZOBUTI, DANIELA SAYURI; DA ROCHA, GUILHERME LUIZ; DA SILVA, HELOINA NATHALLIE MARIANO; COVATTI, CAROLINE; PEREIRA, ELAINE CRISTINA LEITE; FERRETTI, RENATO; MINATEL, ELAINE. Tempol improves redox status in mdx dystrophic diaphragm muscle. International Journal of Experimental Pathology, v. 101, n. 6, p. 289-297, DEC 2020. (17/01638-0)