Mitochondrial damage in patients with long-term corticosteroid therapy: development of oculoskeletal symptoms similar to mitochondrial disease.
Two patients with long-term corticosteroid administration sporadically developed limb muscle wasting followed by ophthalmoplegia, and the skeletal muscle pathology revealed ragged-red fibers (RRFs) with abnormal mitochondria, in addition to the findings of corticosteroid myopathy. The oculoskeletal symptoms of the present cases resemble those of chronic progressive external ophthalmoplegia, a type of mitochondrial disease. The ocular muscles have more RRFs than limb muscles, and large multiple deletions of mitochondrial DNA was detected in ocular and limb muscles of the two patients by PCR but not by Southern blotting. Immunohistochemistry demonstrated that 8-hydroxy-deoxyguanosine (8-OH-dG) and 4-hydroxy-2-nonenal were intensely stained in skeletal muscles of these patients particularly in RRFs. High-performance liquid chromatography with electrochemical detection analysis revealed an increase in 8-OH-dG from mitochondrial DNA. These findings may suggest that long-term corticosteroid administration potentially induces oxidative stress-mediated mitochondrial damage, resulting in the development of the oculoskeletal symptoms in some patients.
Mitsui
Takao
T
First Department of Internal Medicine, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. tmitsui@clin.med.tokushima-u.ac.jp
Umaki
Yoshifumi
Y
Nagasawa
Masakazu
M
Akaike
Masashi
M
Aki
Kenji
K
Azuma
Hiroyuki
H
Ozaki
Shyuji
S
Odomi
Masaaki
M
Matsumoto
Toshio
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003937:Diagnosis, Differential; D005080:Exercise Test; D005260:Female; D017353:Gene Deletion; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology*; D009801:Oculomotor Muscles / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D011239:Prednisolone / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000447:Aldehydes; D000893:Anti-Inflammatory Agents; D019344:Lactic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D011239:Prednisolone; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal