Electron Transport Complex IV ; analysis ; Humans ; Mitochondrial Myopathies ; enzymology ; Staining and Labeling ; Succinate Dehydrogenase ; analysis

The purpose of this study were 1) to determine the earliest pathological changes of germanium dioxide (GeO2)-induced myopathy; 2) to determine the pathomechanism of GeO2-induced myopathy; and 3) to determine the minimal dose of GeO2 to induce myopathy in rats. One hundred and twenty five male and female Sprague-Dawley rats, each weighing about 150 gm, were divided into seven groups according to daily doses of GeO2. Within each group, histopathological studies were done at 4, 8, 16, and 24 weeks of GeO2 administration. Characteristic mitochondrial myopathy was induced in the groups treated daily with 10 mg/kg of GeO2 or more. In conclusion, the results were as follows: 1) The earliest pathological change on electron microscope was the abnormalities of mitochondrial shape, size and increased number of mitochondria; 2) The earliest pathological change on light microscope was the presence of ragged red fibers which showed enhanced subsarcolemmal succinate dehydrogenase and cytochrome c oxidase reactivity; 3) GeO2 seemed to affect the mitochondrial oxidative metabolism of muscle fibers; 4) GeO2 could induce mitochondrial myopathy with 10 mg/kg of GeO2 for 4 weeks or less duration in rats.
Animal ; Cytochrome-c Oxidase/metabolism ; Female ; Germanium/toxicity* ; Histocytochemistry ; Male ; Mitochondrial Myopathies/pathology ; Mitochondrial Myopathies/enzymology ; Mitochondrial Myopathies/chemically induced* ; Muscles/ultrastructure ; Muscles/enzymology ; Rats ; Rats, Sprague-Dawley ; Succinate Dehydrogenase/metabolism