Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy

• Published in: American Journal of Physiology: Cell Physiology 2006-02, Vol.290 (2), p.C616-C625
• Main Authors: Dorchies, Olivier M, Wagner, Stephanie, Vuadens, Ophelie, Waldhauser, Katri, Buetler, Timo M, Kucera, Pavel, Ruegg, Urs T
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Camellia sinensis - chemistry; Catechin - analogs & derivatives; Catechin - pharmacology; Catechin - therapeutic use; Diet; Disease Models, Animal; Free Radical Scavengers - pharmacology; Humans; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle Contraction - physiology; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Dystrophy, Duchenne - drug therapy; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - pathology; Pentoxifylline - pharmacology; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Preparations - pharmacology; Plant Preparations - therapeutic use
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00425.2005

1 Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Geneva; and 2 Institute of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland Submitted 23 August 2005 ; accepted in final form 27 September 2005 Duchenne muscular dystrophy is a frequent muscular disorder caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that contributes to the stabilization of muscle fiber membrane during muscle activity. Affected individuals show progressive muscle wasting that generally causes death by age 30. In this study, the dystrophic mdx 5Cv mouse model was used to investigate the effects of green tea extract, its major component (–)-epigallocatechin gallate, and pentoxifylline on dystrophic muscle quality and function. Three-week-old mdx 5Cv mice were fed for either 1 or 5 wk a control chow or a chow containing the test substances. Histological examination showed a delay in necrosis of the extensor digitorum longus muscle in treated mice. Mechanical properties of triceps suræ muscles were recorded while the mice were under deep anesthesia. Phasic and tetanic tensions of treated mice were increased, reaching values close to those of normal mice. The phasic-to-tetanic tension ratio was corrected. Finally, muscles from treated mice exhibited 30–50% more residual force in a fatigue assay. These results demonstrate that diet supplementation of dystrophic mdx 5Cv mice with green tea extract or (–)-epigallocatechin gallate protected muscle against the first massive wave of necrosis and stimulated muscle adaptation toward a stronger and more resistant phenotype. pharmacotherapy; muscular disorders; dystrophic mdx 5cv mouse; muscle mechanical properties; muscle histology Address for reprint requests and other correspondence: U. T. Ruegg, Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, Univ. of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland (e-mail: urs.ruegg{at}pharm.unige.ch )