Raya A, Gallego J, Bosch-Morell F, Romá J, Romero F J
Department of Physiology, University of Valencia, Spain.
Free Radic Biol Med. 1995 Nov;19(5):665-7. doi: 10.1016/0891-5849(95)00031-r.
Administration of high doses (150-250 mg/kg body weight) of phenytoin (DPH) promote a 40% decrease in glutathione (GSH) content of rat sciatic nerve. This DPH-induced GSH depletion is accompanied with an electrophysiological impairment of peripheral neuromuscular function. H7 (20 mg/kg body weight IP, 30 min prior to DPH), a protein kinase C inhibitor, was able to prevent the DPH-induced GSH depletion only at the lower DPH dose used. This same inhibitor completely prevented the electrophysiological impairment at the lower DPH dose, and only partially at the higher DPH dose used. These results confirm the hypothesis of a DPH-dependent activation of PKC (that might be triggered by, or be the consequence of, the reduction of the intracellular antioxidant GSH), as one of the pathophysiological mechanisms involved in DPH-induced neurotoxicity.
给予高剂量（150 - 250毫克/千克体重）的苯妥英（DPH）会使大鼠坐骨神经中的谷胱甘肽（GSH）含量降低40%。这种由DPH诱导的GSH耗竭伴随着外周神经肌肉功能的电生理损伤。H7（20毫克/千克体重，腹腔注射，在DPH给药前30分钟），一种蛋白激酶C抑制剂，仅在使用的较低DPH剂量下能够预防DPH诱导的GSH耗竭。相同的抑制剂在较低DPH剂量下完全预防了电生理损伤，而在使用的较高DPH剂量下仅部分预防。这些结果证实了PKC的DPH依赖性激活的假说（这可能由细胞内抗氧化剂GSH的减少引发或作为其结果），作为DPH诱导的神经毒性所涉及的病理生理机制之一。
