Tempol improves redox status in mdx dystrophic diaphragm muscle

• Published in: International journal of experimental pathology Vol. 101; no. 6; pp. 289 - 297
• Main Authors: Hermes, Túlio de Almeida, Mizobuti, Daniela Sayuri, Rocha, Guilherme Luiz, Silva, Heloina Nathalliê Mariano, Covatti, Caroline, Pereira, Elaine Cristina Leite, Ferretti, Renato, Minatel, Elaine
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2020; John Wiley and Sons Inc
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Catalase; Cyclic N-Oxides - pharmacology; Diaphragm; Diaphragm (Anatomy); Diaphragm - drug effects; Diaphragm - physiopathology; diaphragm muscle; Disease Models, Animal; Duchenne's muscular dystrophy; dystrophic muscles; Dystrophy; Female; Gene expression; Glutathione; Glutathione peroxidase; Homeostasis; Homeostasis - drug effects; Human pathology; Humans; Injections, Intraperitoneal; Male; Manganese; mdx mice; Mice; Mice, Inbred mdx; Muscles; Muscular dystrophy; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - physiopathology; Original; Oxidants; Oxidation-Reduction - drug effects; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Parameters; Peroxidase; Protein adducts; redox homeostasis; Reductases; Rodents; Saline solutions; Spin Labels; Superoxide dismutase; Superoxide Dismutase - metabolism; Tempol; redox homeostasis; diaphragm muscle; dystrophic muscles; oxidative stress; mdx mice
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1111/iep.12376

Oxidative stress is a critical element in relationship to the pathophysiology of Duchenne muscular dystrophy (DMD). In the mice the diaphragm (DIA) is most resembles the dystrophic human pathology. In this study we have evaluated the consequences of a synthetic antioxidant (tempol) on oxidative stress parameters in the DIA muscle of mdx mice. The mdx mice were separated into two groups: mdx, the control group receiving intraperitoneal (i.p.) injections of saline solution (100 µL), and mdxT, the treated group receiving i.p. injections of tempol (100 mg/kg). The tempol‐treated group showed reduced oxidative stress markers, decreasing the dihydroethidium reaction (DHE) area; autofluorescent lipofuscin granules; and 4‐hydroxynonenal (4‐HNE)‐protein adduct levels. DIA muscle of mdx mice. At the same time, the manganese‐superoxide dismutase 2 (SOD2) levels were increased in the tempol‐treated group. In addition, the tempol‐treated group showed reduced levels of glutathione‐disulphide reductase (GSR), glutathione peroxidase 1 (GPx1) and catalase (CAT) in immunoblots. The tempol‐treated group has also shown lower relative gene expression of SOD1, CAT and GPx than the non‐treated group. Our data demonstrated that tempol treatment reduced oxidant parameters and increased anti‐oxidant SOD2 levels in the DIA muscle of mdx mice, which may contribute to the normalization of the redox homeostasis of dystrophic muscles.