The possible protective effect of N-acetyl-L-cysteine and folic acid in combination against aspartame-induced cerebral cortex neurotoxicity in adult male rats: a light and transmission electron microscopic study.

The purpose of this study is to investigate structural and ultrastructural alterations in the rat's brain cerebral cortex after aspartame (ASP) treatment and to evaluate the possible ameliorating role of N-acetyl-L-cysteine (NAC) and folic acid (FA). Forty adult rats were divided into four equal groups: Group I, received appropriate vehicle only and served as control. Group II, received oral doses of both NAC (600 mg/kg body weight (b.w.)) and FA (12 mg/kg b.w.) daily for 42 days. Group III, received oral doses of ASP (500 mg/kg b.w.) daily for 42 days. Group IV, received both NAC and FA, concurrently with ASP at the same doses, route and period of administration of the previous groups. Histological examination of the cerebral cortex of ASP-treated rats showed severe degenerative changes, especially in the nerve cells. Some of these cells appeared shrunken, irregular in shape, while the others appeared swollen and were surrounded by pericellular halos. Immunohistochemical and morphometric study of ASP-treated group revealed a weak B-cell lymphoma-2 (Bcl-2) immunoexpression in the cytoplasm of many cells, while intense positive immunoreaction for glial fibrillary acidic protein (GFAP) was observed in the cytoplasm and processes of astrocytes compared to control group with statistically significant difference (p < 0.001). Light microscopic results were confirmed by ultrastructural findings. However, NAC and FA in combination had an obvious protective effect against ASP-induced injury in the rat's cerebral cortex. In conclusion, these results suggested that NAC combined with FA can ameliorate the toxic effect of ASP on the rat's cerebral cortex.