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 were assessed in rat posterior tibial and proximal sciatic nerves. Animals 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 microanalysis demonstrated that oral 2,5-HD intoxication produced temporally-dependent disruptions of Na, P, Cl, K and Mg distributions in Schwann cells of proximal and distal nerve regions. On both a dry and wet weight basis, cytoplasmic Na and Cl concentrations increased, while P, K and Mg levels declined relative to control values. In contrast, intraperitoneal administration was associated with minimal changes in regional glial cell elemental concentrations. Moreover, neither route of intoxication altered the elemental composition nor water content of myelin. Thus, oral but not i.p. intoxication of rats with 2,5-HD causes perturbation of elemental distributions in peripheral nerve Schwann cells. Although the pattern of elemental disruption caused by oral administration is typical of cellular injury, the route-dependent nature draws into question the overall mechanistic relevance of this effect.