Exposure of weanling rats to a diet containing 1% elemental
tellurium causes segmental
demyelination of peripheral nerve, and an inhibition of
squalene epoxidase. This inhibition is thought to be the mechanism of action leading to
demyelination.
Tellurite appears to be the active inhibitory species in a cell-free system but the active species in vivo is unknown. We examined
potassium tellurite (K2TeO3) and three organotellurium compounds for their ability to inhibit
squalene epoxidase in Schwann cell cultures and to induce
demyelination in weanling rats. K2TeO3 had no effect on
squalene epoxidase activity in cultured Schwann cells and caused no
demyelination in vivo. All three organotellurium compounds caused inhibition of
squalene epoxidase in vitro and caused
demyelination in vivo. (CH3)2TeCl2 was the most potent of these compounds and its neuropathy most resembled that caused by elemental
tellurium. These data are consistent with the hypothesis that
tellurium-induced
demyelination is a result of
squalene epoxidase inhibition and suggest that a dimethyltelluronium compound may be the neurotoxic species presented to Schwann cells in vivo.