ROLE OF ORGANOTELLURIUM SPECIES IN TELLURIUM NEUROPATHY

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 vi vo is unknown. We examined potassium tellurite (K2TeO3) and three orga notellurium 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 Schwa nn cells and caused no demyelination in vivo. All three organotelluriu m compounds caused inhibition of squalene epoxidase in vitro and cause d demyelination in vivo. (CH3)(2)TeCl2 was the most potent of these co mpounds and its neuropathy most resembled that caused by elemental tel lurium. These data are consistent with the hypothesis that tellurium-i nduced demyelination is a result of squalene epoxidase inhibition and suggest that a dimethyltelluronium compound may be the neurotoxic spec ies presented to Schwann cells in vivo.