Vigabratine increases superoxide dismutase activity in striatum of rat after pilocarpine-induced seizures

Rivelilson Mendes de Freitas

BACKGROUND: Pilocarpine-induced seizures have been suggested to be mediated by increases in oxidative stress. Current studies have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures. OBJECTIVES: This study investigated the pharmacological actions of vigabatrin on behavioral changes and superoxide dismutase (SOD) activity in striatum of adult rats. METHODS: Adult rats (2 months old) were used in the experiments and divided into four groups. The first was treated with 0.9% saline (control group). The second group was treated with pilocarpine (400 mg/kg, i.p., P400 group). The third group received vigabatrin alone (500 mg/kg, i.p., VGB group) and the fourth group was treated with vigabatrin (500 mg/kg, i.p.) and 30 minutes later received pilocarpine (400 mg/kg, i.p., VGB + P400 group). The animals which had seizures and status epilepticus (SE) and did not die within 24 hours of observation were sacrificed to perform the neurochemical studies. RESULTS: Behavioral studies showed that the administration of pilocarpine produces peripheral cholinergic signs, tremors and stereotyped movements in all animals. An amount of 75% of those rats developed to seizures and SE. In turn, the pre-treatment with vigabatrin produced a 50% reduction in the rate of seizures and SE. Regarding the neurochemical studies, there were no changes in the striatal SOD activity in P400 group as compared to the control group. However, in the VGB + P400 group it was verified significant increases in SOD activity of 34% and 35% as compared to control and P400 group, respectively. DISCUSSION: Our results indicate that behavioral changes occur during seizures, but SOD activity remained unaltered during the acute phase of the convulsive crisis. Our findings suggest that the anticonvulsant effect of vigabatrin may be the result of modulation of this enzyme, in an attempt to protect the animal against neuronal damage produced by seizures. Further pharmacological studies will be carried out in order to clarify the mechanism of action of vigabatrin on the pilocarpine-induced epilepsy model.

Striatum; seizures; pilocarpine; superoxide dismutase; vigabatrin

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