Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame

Abstract

Aspartame is a synthetic sweetener widely used by individuals with restriction diets of sucrose, glucose or fructose or by those seeking wight loss. Several studies have indicated that its use is related to changes in the central nervous system, as well as to the induction of oxidative stress. However, the mechanisms responsible for such effects are not fully understood, as well as the potential of antioxidant compounds, such as N-acetylcysteine, in mitigating such damages. Thus, this study evaluated the effects of N-acetylcysteine (NAC) (163 mg/kg, i.p) on behavioral and oxidative parameters against the long-term (90 days) administration of aspartame (80 mg/kg, v.o) in brain regions of mice. For this purpose, Swiss albino male mice were divided in three groups: control – received both aspartame and Nacetylcysteine vehicles; ASP – received aspartame, and the N-acetylcysteine vehicle; and ASP-NAC – received both treatments, aspartame and N-acetylcysteine. Aspartame was administered for 90 days, while NAC was injected only in the last 30 days. In the last week of the experimental period, the animals had their behavior evaluated through the open field test. At the end of the 90 days, the animals were anesthetized and euthanized for the removal of the brain and separation of the following regions: cerebral cortex, hippocampus and cerebellum, in which was held the research of the oxidative stress biomarkers and the gene expression of catalytic subunit of glutamate cysteine ligase (Gclc), cystathionin γ-lyase (Cth) and thioredoxin 1 (Trx1). The results showed that the mice treated with aspartame and NAC presented a decrease in the number of crossings and an increase in the time spent in the central area in relation to the control animals and treated with aspartame alone. Although it did not alter the thioredoxin system, the administration of aspartame caused severe depletion in non-protein thiois (NPSH) levels as well as glutathione peroxidase (GPx) activity. Both changes were restored by treatment with NAC. Aspartame also triggered a decrease in Gclc and Cth mRNA levels. Treatment with NAC restored Gclc levels. It is concluded from these results that, although it did not alter the thioredoxin system, treatment with aspartame caused a severe depletion of NPSH levels, which may be due to the decrease in Gclc and Cth mRNA levels, demonstrating that the mechanism of action of aspartame toxicity is more related to the GSH system. In addition, the results suggest an anxiolytic effect of NAC in animals treated with aspartame. NAC was able to restore most of the changes in the GSH-related system in brain regions after long-term ingestion of aspartame.