DISRUPTION OF SCHWANN-CELL ELEMENTAL COMPOSITION IS NOT A PRIMARY NEUROTOXIC EFFECT OF 2,5-HEXANEDIONE

The effects of 2,5-hexanedione (2,5-HD) on elemental composition (Na, P, S, Cl, K, Ca, Mg) and water content of Schwann cells and myelin wer e assessed in rat posterior tibial and proximal sciatic nerves. Animal s were intoxicated with 2,5-HD by two routes of administration: oral ( 0.4% in drinking water for 78, 85 or 104 days) and intraperitoneal (i. p.; 0.4 gm/kg/day x 11, 18 or 30 days). Electron probe X-ray microanal ysis demonstrated that oral 2, 5-HD intoxication produced temporally-d ependent disruptions of Na, P, Cl, K and Mg distributions in Schwann c ells of proximal and distal nerve regions. On both a dry and wet weigh t basis, cytoplasmic Na and CI concentrations increased, while P, K an d Mg levels declined relative to control values. In contrast intraperi toneal administration was associated with minimal changes in regional glial cell elemental concentrations. Moreover, neither route of intoxi cation altered the elemental composition nor water content of myelin. Thus, oral but not i.p. intoxication of rats with 2,5-HD causes pertur bation of elemental distributions in peripheral nerve Schwann cells. A lthough the pattern of elemental disruption caused by oral administrat ion is typical of cellular injury, the route-dependent nature draws in to question the overall mechanistic relevance of this effect. (C) 1994 Intox Press, Inc.