Partial cytochrome c oxidase deficiency and cytoplasmic bodies in patients with zidovudine myopathy.
A histochemical study of cytochrome c oxidase (CCO) was performed in the muscles from eight patients with full-blown zidovudine myopathy. All patients had ragged-red fibres (total cumulative count: 160) and myofilamentous changes, that predominated in type 1 fibres and included diffuse or punch-out myofibrillar loss (75 affected fibres) and constant cytoplasmic body formation (106 affected fibres). Inflammatory infiltrates were present in four out of eight patients. A partial CCO deficiency (22-47% of fibres; both types 1 and 2 affected) was detected in all cases, and contrasted with the normal or increased succinate dehydrogenase activity observed in most fibres. Among CCO-deficient fibres, 71% were normal on trichrome, but all ragged-red fibres were CCO-negative. Myofilamentous changes were restricted to CCO-deficient fibres. The present study strongly supports the idea that mitochondrial toxicity is the specific mechanism of zidovudine myopathy.
Chariot
P
P
Département de Pathologie (Neuropathologie), Hôpital Henri Mondor, Créteil, France.
Gherardi
R
R
D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D000328:Adult; D001284:Atrophy; D030401:Cytochrome-c Oxidase Deficiency; D015497:HIV-1; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D009210:Myofibrils / Q000187:drug effects / Q000648:ultrastructure*; D012508:Sarcolemma / Q000187:drug effects / Q000648:ultrastructure*; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D015215:Zidovudine