Background: Food additives are substances added to food to improve its safety, freshness, taste, texture, or appearance. They include aroma enhancer eg : monosodium glutamate(MSG) or sweetener eg.: aspartame (ASP). Aim of the Study: This current study was performed to study the microscopic alterations induced by MSG, ASP individually and in combination and the possible protective effect of astaxanthin (AST) on those induced changes. Materials and Methods: Forty nine adult male albino rats were used in this study divided into; control group (fourteen rats) two rats for each experimental group and experimental group (thirty five rats) subdivided into seven subgroups:ASP group, MSG group, ASP andMSG group,AST group,ASP andAST group, MSG andAST group, ASPandMSG andAST group. Oral administration was done in the morning daily for 6 weeks for all groups. When the duration of the study ended, blood samples were collected from rat tail and paraffin sections were prepared from the cerebral hemisphere of each animal. They were subjected to hematoxylin and eosin stain and immunohistochemical stain for Caspase3 and Glial Fibrillary Acidic Protein (GFAP). Statistical analysis were done for assessment of body weight, reduced glutathione (GSH) and tumor necrosis factor α (TNF-α) level. Results: The groups that received ASP (I), MSG (II) individually or in combination (III) exhibited shrunken cells with darkly stained nuclei and surrounded with pericellular haloes and some areas even revealed loss of the cells with increase in immunoreactivity for GFAP and Caspase 3. These groups also showed elevation in the level of TNFα and decrease in the level of GSH. On treatment with AST groups V, VI and VII showed reduced pycknosis, decreased immunoreactivity for GFAP and Caspase 3. It also showed reduction in the level of TNFα and increased level of GSH. Conclusion: ASP and MSG individually or in combination induce alternation in hippocampus and AST administration ameliorate those changes

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