Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

BACKGROUND:Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione,known as one of the compounds of antioxidant defense,has been shown to inhibit convulsions.Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE:To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN,TIME,AND SETTING:A randomized,controlled,animal experiment.The study was performed at the Department of Physiology,Gaziantep University and Department of Chemistry-Biochemistry,Kahramamaras Sutcu Imam University in 2006. MATERIALS:Pentylenetetrazole and glutathione were purchased from Sigma,USA. METHODS:A total of 80 mice were assigned to 8 groups(n=10):normal control,saline control (1 mL normal saline),convulsive pentylenetetrazole(single intraperitoneal administration of pentylenetetrazole,60 mg/kg),convulsive pentylenetrazole plus glutathione(single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione),five-dose glutathione(intraperitoneal injection of 200 mg/kg glutathione respectively at 1,3,5,7,and 10 days),single-dose glutathione (single administration of 200 mg/kg glutathione),pentylenetetrazole kindling(intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1,3,5,7,and 10 days),and pentylenetetrazole kindling plus glutathione group(intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1,3,5,7,and 10 days). MAIN OUTCOME MEASURES:All mice were sacrificed 1 hour after the last administration.Brain nitric oxide levels were determined by spectrophotometry. RESULTS:There were no significant differences in nitric oxide levels between the normal control, saline control,five-dose glutathione,and single-dose glutathione groups(P>0.05).Nitric oxide levels in the cerebral hemisphere and cerebellum were significantly less in the convulsive pentylenetetrazole group,compared with the convulsive pentylenetetrazole plus glutathione group (P<0.01),and levels in the pentylenetetrazole kindling group were remarkably greater than the remaining groups(P<0.01).Brain nitric oxide levels in all groups gradually decreased from the right brain stem to the left brain stem,cerebellum,left cerebral hemisphere,and right cerebral hemisphere. CONCLUSION:Glutathione regulated nitric oxide levels in various brain regions of pentylenetetrazole-induced kindling models,and did not affect nitric oxide levels in the control mice. These results indicated that glutathione played a role when nitric oxide was over-produced.In addition,the brain stem exhibited the highest levels of nitric oxide in both control mice and pentylenetetrazole-induced kindling models.