6533b82dfe1ef96bd1290955
RESEARCH PRODUCT
Phenytoin-induced glutathione depletion in rat peripheral nerve
Angel RayaFrancisco J. RomeroJuan GallegoFrancisco Bosch-morellJoaquín Romásubject
MalePhenytoinAntioxidantmedicine.medical_treatmentAction PotentialsIn Vitro TechniquesPharmacologymedicine.disease_causeBiochemistryPiperazineschemistry.chemical_compound1-(5-Isoquinolinesulfonyl)-2-MethylpiperazinePhysiology (medical)polycyclic compoundsmedicineAnimalsEnzyme InhibitorsRats WistarMuscle SkeletalEvoked PotentialsProtein Kinase CProtein kinase CMotor NeuronsAnalysis of Variancetechnology industry and agricultureNeurotoxicityGlutathioneIsoquinolinesmedicine.diseaseGlutathioneSciatic NerveRatsKineticschemistryBiochemistryPhenytoinAnticonvulsantslipids (amino acids peptides and proteins)Sciatic nerveOxidative stressIntracellularmedicine.drugdescription
Abstract 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1995-11-01 | Free Radical Biology and Medicine |