Myoinositol inhibits proliferation of cultured Schwann cells: evidence for neurotoxicity of myoinositol.
To determine whether so-called uraemic toxins exhibit direct toxic effects on Schwann cells, the latter were cultured in a monolayer with the addition of uraemic toxins. Proliferation of Schwann cells was estimated with [3H]-thymidine incorporation into DNA synthesis. Myoinositol, methylguanidine, guanidinosuccinic acid, parathyroid hormone, phenol, p-cresol, 4-hydroxyphenylacetic acid, 4-hydroxybenzoic acid, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were added at various concentrations to the culture medium. Addition of myoinositol at concentrations between 50 and 100 micrograms/ml, values analogous to those in in a dose-dependent way. Myoinositol also inhibited axolemma-stimulated proliferation of Schwann cells. The other compounds at concentrations occurring in uraemic serum did not show any toxic effect on Schwann cells. These results suggest that myoinositol has a neurotoxic effect on Schwann cells, and uraemic polyneuropathy seemed to be caused by a defect in maintaining normal myelin due to accumulation of myoinositol.
Niwa
T
T
Department of Internal Medicine, Nagoya University Branch Hospital, Japan.
Sobue
G
G
Maeda
K
K
Mitsuma
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D007294:Inositol / Q000633:toxicity*; D009422:Nervous System Diseases / Q000209:etiology; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014118:Toxins, Biological / Q000633:toxicity; D014511:Uremia / Q000150:complications
D014118:Toxins, Biological; D007294:Inositol; D004247:DNA