Subcutaneous injection,from birth,of epigallocatechin-3-gallate,a component of green tea,limits the onset of muscular dystrophy in <Emphasis Type="Italic">mdx</Emphasis> mice: a quantitative histological,immunohistochemical and electrophysiological study |
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Authors: | Yoshiko Nakae Katsuya Hirasaka Junpei Goto Takeshi Nikawa Masayuki Shono Mizuko Yoshida Peter J Stoward |
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Institution: | (1) Department of Oral and Maxillofacial Anatomy, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan;(2) Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan;(3) Support Centre for Advanced Medical Sciences, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan;(4) Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, Kodaira 187-8502, Japan;(5) College of Life Sciences, University of Dundee, Dundee, DD1 4HN, UK;(6) Present address: Laboratory of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences, University of Geneva, Sciences II 4-438B, 30 Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland |
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Abstract: | Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate
(EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5 mg/kg body weight in saline) was injected
subcutaneously 4× a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8 weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology
of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin
granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers
in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied
by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue
and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to
fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly
by 17%, partially compensating for the lack of dystrophin expression. |
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Keywords: | Epigallocatechin-3-gallate Muscular dystrophy Mdx mice Duchenne muscular dystrophy Quantitative histology Lipofuscin Utrophin Creatine kinase |
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