(–)‐Epicatechin improves mitochondrial‐related protein levels and ameliorates oxidative stress in dystrophic δ‐sarcoglycan null mouse striated muscle

Citations Over Time

Abstract

Muscular dystrophies (MDs) are a group of heterogeneous genetic disorders characterized by progressive striated muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism of disease pathogenesis remains unclear. The presence of oxidative stress (OS) is known to contribute to the pathophysiology and severity of the MD. Mitochondrial dysfunction is observed in MD, and probably represents an important determinant of increased OS. Experimental antioxidant therapies have been implemented with the aim of protecting against disease progression, but results from clinical trials have been disappointing. In this study, we explored the capacity of the cacao flavonoid (-)-epicatechin (Epi) to mitigate OS by acting as a positive regulator of mitochondrial structure/function endpoints and redox balance control systems in skeletal and cardiac muscles of dystrophic, δ-sarcoglycan (δ-SG) null mice. Wild-type or δ-SG null 2.5-month-old male mice were treated via oral gavage with either water (controls) or Epi (1 mg·kg(-1) , twice daily) for 2 weeks. The results showed significant normalization of total protein carbonylation, recovery of the glutathione/oxidized glutathione ratio and enhanced superoxide dismutase 2, catalase and citrate synthase activities with Epi treatment. These effects were accompanied by increases in the protein levels of thioredoxin, glutathione peroxidase, superoxide dismutase 2, catalase, and mitochondrial endpoints. Furthermore, we found decreases in heart and skeletal muscle fibrosis, accompanied by an improvement in skeletal muscle function, with treatment. These results warrant further investigation of Epi as a potential therapeutic agent to mitigate MD-associated muscle degeneration.

Related Papers

• → Protective Enzymes Against Activated Oxygen Species in Wheat (Triticum aestivum L.) Seedlings: Responses to Cold Acclimation(1999)108 cited
• → Comparative studies of antioxidant enzymes in red-blooded and white-blooded antarctic teleost fish. pagothenia bernacchii and Chionodraco hamatus(1993)30 cited
• → Superoxide dismutase: a contaminant of bovine catalase (Short Communication)(1973)66 cited
• → Effects of superoxide dismutase and catalase on central nervous system toxicity of hyperbaric oxygen(1980)15 cited
• Superoxide dismutase and glutathione peroxidase activities in rat pineal gland.(1992)