PHENYTOIN-INDUCED GLUTATHIONE DEPLETION IN RAT PERIPHERAL-NERVE

Administration of high doses (150-250 mg/kg body weight) of phenytoin (DPH) promote a 40% decrease in glutathione (GSH) content of rat sciat ic nerve. This DPH-induced GSH depletion is accompanied with an electr ophysiological impairment of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior to DPH), a protein kinase C inhibi tor, was able to prevent the DPH-induced GSH depletion only at the low er DPH dose used. This same inhibitor completely prevented the electro physiological impairment at the lower DPH dose, and only partially at the higher DPH dose used. These results confirm the hypothesis of a DP H-dependent activation of PKC (that might be triggered by, or be the c onsequence of, the reduction of the intracellular antioxidant GSH), as one of the pathophysiological mechanisms involved in DPH-induced neur otoxicity.