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

Abstract

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. To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. 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. 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). All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. 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. 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.