Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle |
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Authors: | Takao Mitsui Hiroyuki Azuma Masakazu Nagasawa Takahiko Iuchi Masashi Akaike Masaaki Odomi Toshio Matsumoto |
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Affiliation: | (1) First Department of Internal Medicine School of Medicine The University of Tokushima Kuramoto-3-18-15 Tokushima 770-8503, Japan Tel.: +81-886/31-7120 Fax: +81-886/33-7121 E-Mail: tmitsui@clin.med.tokushima-u.ac.jp, JP;(2) Analytical Department Formulation Research Institute Otsuka Pharmaceutical Co.,Ltd. 463-10 Kasugano Kawauchicho Tokushima 771-0192, Japan, JP |
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Abstract: | Corticosteroid myopathy is a major clinical problem in patients undergoing chronic corticosteroid treatment and shows insidious and progressive muscle atrophy in proximal limbs. Although several mechanisms underlying the pathophysiology of muscle injury have been postulated, precise pathogenesis is still not clear. We evaluated the mitochondrial functions in patients receiving corticosteroids compared with those in healthy controls or patients not receiving corticosteroids. The serum levels and total production of lactate were investigated by an aerobic exercise test using a bicycle ergometer. Mitochondrial respiratory activities and oxidative damage in biopsied skeletal muscles were also studied. The results of aerobic exercise tests revealed a significant overproduction of lactate in patients treated with corticosteroids (p < 0.005), which was positively correlated with total corticosteroid doses administered (p < 0.0001). In these patients, mitochondrial enzyme activity in complex I was significantly decreased (p < 0.05) and oxidative damage of biopsied skeletal muscle was remarkable both in mitochondrial and nuclear DNAs (p < 0.001). The results suggest that chronic corticosteroid administration induces mitochondrial dysfunction and oxidative damage in skeletal muscles, which may be the pathogenesis, at least in part, of corticosteroid-induced myopathy. Received: 5 November 2001 Received in revised form: 4 February 2002 Accepted: 7 February 2002 |
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Keywords: | corticosteroid myopathy mitochondrial respiratory activity oxidative damage aerobic exercise biopsied skeletal muscle |
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