Experimental germanium dioxide-induced neuropathy in rats.
We report an experimental model of germanium dioxide (GeO2)-induced neuropathy in rats. More than 6 months administration of GeO2 to young rats produced neuropathy characterized by segmental demyelination/remyelination and nerve edema. Electron microscopic studies demonstrated that changes in Schwann cells, such as an increased cytoplasmic volume or disintegration of the cytoplasm, were the earliest pathological findings. Schwann cell mitochondria contained high electron-dense materials. Subsequent removal of necrotic Schwann cell debris and myelin by invading macrophages was evident. These findings suggested that the Schwann cells themselves are the primary target of the toxin. The deposition of electron-dense granules in the intra-axonal vesicles, which was suggestive of glycogen granules in mitochondria, was observed in the advanced stage of the neuropathy. The findings of endoneurial edema with splitting of myelin lamellae were noted at the early stage of demyelination. Nerve edema may be the result of GeO2-induced endothelial cell injury.
Matsumuro
K
K
Third Department of Internal Medicine, Kagoshima University School of Medicine, Japan.
Izumo
S
S
Higuchi
I
I
Ronquillo
A T
AT
Takahashi
K
K
Osame
M
M
D000818:Animals; D016587:Antimutagenic Agents / Q000633:toxicity*; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005857:Germanium / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D013997:Time Factors
D016587:Antimutagenic Agents; D005857:Germanium; C040516:germanium oxide