Date Published: April 22, 2019
Publisher: Public Library of Science
Author(s): Túlio de Almeida Hermes, Rafael Dias Mâncio, Aline Barbosa Macedo, Daniela Sayuri Mizobuti, Guilherme Luiz da Rocha, Valéria Helena Alves Cagnon, Elaine Minatel, James M. Ervasti.
Considering potential Tempol effects on mdx muscle fibers, in this study we evaluated its effects on relevant dystrophic phenotypic characteristics, such as muscle degeneration, inflammatory process and angiogenesis, which as yet have not been investigated. Mdx mice were randomly assigned into three groups: mdxS, the control group receiving intraperitoneal (i.p.) injections of saline solution (100μL); mdxP, positive control group receiving prednisolone (1mg/kg) by oral gavage; and mdxT, treated group receiving i.p. injections of tempol (100 mg/kg). C57BL/10 mice were also used as controls. Tempol treatment promoted gain in muscle strength and reduced myonecrosis and inflammatory response in the dystrophic diaphragm (DIA) and biceps brachii (BB) muscles. No evidence of Tempol’s beneficial performance on angiogenesis in DIA and BB mdx muscles was found. The findings presented here show that Tempol treatment improves dystrophic phenotype, supporting its use as a potential therapeutic strategy in DMD.
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, whose genetic defect is identified in the X chromosome gene that encodes the intracellular protein dystrophin . DMD patients usually show motor difficulties by the age of six and the muscle weakness progresses, leaving patients wheelchair-bound by their teens, with death occurring in their twenties owing to respiratory and cardiovascular failure .
Tempol is a redox-cycling (catalytic), metal-independent, and membrane permeable superoxide dismutase mimetic . Beneficial Tempol effects have been observed in several diseases . The advantageous Tempol effects in the dystrophic skeletal muscle of mdx mice were demonstrated in the results herein by means of gain muscle strength, muscle degeneration/regeneration reduction and inflammatory response decrease.