Estudo do efeito neuroprotetor da N-Acetilcisteina em ratas periadolescentes submetidas a convulsão pelo abrasamento induzido por nicotina

Abstract

Nicotine (NIC) is the major component of tobacco smoking being one of the most abused substances worldwide. One important pharmacological effect of NIC is the induction of seizures. In this context it was previously proposed that NIC repeated administration is capable of inducing kindling, a form of sensitization related to the induction of behavioral alterations, among then seizures. Kindling is being used as a tool for the study of progression in a wide range of neuropsychiatric disorders. Recently our research group evidenced that periadolescent female rats were more susceptible to NIC-induced kindling demonstrating a participation of prooxidant mechanisms in this response. Based on these evidences, the present study had the goal to study the benefits of the administration of N-acetylcysteine (NAC), an antioxidant drug, in the prevention of NIC-induced seizures. To do this, female Wistar periadolescent rats (60-80 g) were used. The animals were administered NIC (2mg/Kg/day, i.p.); NAC (90, 180 or 270 mg/Kg/day, i.p.) alone or combined with NIC (NAC+NIC) or distilled water during 19 days. The animal’s behavior was evaluated at 1st, 8th, 15th and 19th days, using Racine Scale (seizure grades 1 to 5). At the end of treatment (19th day), animals were killed and their prefrontal cortex, hippocampus and striatum dissected. Homogenates were used to evaluate SOD activity, GSH levels, nitrite levels (as an indirect nitric oxide measurement), and lipid peroxide generation by measuring the substances that react with thiobarbituric acid. Animals treated with NAC presented a decrement in seizure activity. The SOD activity levels were decreased in group that received NAC+NIC. On the other hand, GSH levels had a significant increment in both groups treated with NAC and NAC+NIC. The lipid peroxidation level was reduced in the group that received NAC+NIC, and there was no change in nitrite levels in any group. The conclusion was that NAC presented a neuroprotective effect when diminished the lipid peroxidation level in animals exposed to nicotine-induced kindling.