Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle.
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.
Mitsui
Takao
T
First Department of Internal Medicine, School of Medicine, The University of Tokushima, Kuramoto-3-18-15, Tokushima 770-8503, Japan. tmitsui@clin.med.tokushima-u.ac.jp
Azuma
Hiroyuki
H
Nagasawa
Masakazu
M
Iuchi
Takahiko
T
Akaike
Masashi
M
Odomi
Masaaki
M
Matsumoto
Toshio
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000032:analysis; D005080:Exercise Test; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects*; D009097:Multienzyme Complexes / Q000032:analysis; D018482:Muscle, Skeletal / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000032:analysis; D019289:Pyruvic Acid / Q000097:blood; D013385:Succinate Dehydrogenase / Q000032:analysis; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D009097:Multienzyme Complexes; D019344:Lactic Acid; D019289:Pyruvic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D003849:Deoxyguanosine