A COCKTAIL OF CAFFEINE AND ACETYLSALICYLIC ACID ADMINISTRATION IN COMBINATION WITH ETHANOL CAUSES OXIDATIVE STRESS AND INFLAMMATORY RESPONSE IN THE HIPPOCAMPAL CA1 OF ADULT WISTAR RATS

Olufunto Omodele Adeleye* and Olatunde Owoeye

Ethanol, a psychoactive drug commonly used for recreational purposes carries a major health risk due to its abuse, and this has been associated with early onset of degenerative disorders. Alcohol abusers are found to combine it with an analgesic containing a cocktail of caffeine and acetyl salicylic acid (CASA). The CASA is a common over- the- counter drug used for the treatment of body pains, cold, headache and fever, which also reverses the depressant effect of alcohol. Neurotoxicity has been reported with chronic consumption of CASA with alcohol, however its neurotoxic effects on the hippocampus is not fully elucidated. Therefore, this study was designed to investigate the structural and functional alterations of the hippocampus following chronic administration of ethanol and CASA in Wistar rats. Forty adult Wistar rats of both sexes (160.00±6.23g) were divided into four groups (n=10): Control group (distilled water), CASA (31mg/kg), Ethanol (30% v/v) and CASA+ethanol (31mg/kg CASA and 30%v/v of ethanol). All substances were administered daily by oral gavage for 60 days. At the end of administration, the rats were sacrificed and brain samples obtained for biochemical and histological analysis. The hippocampal tissues were analyzed for Malondialdehyde (MDA), Nitric Oxide (NO), Reduced Glutathione (GSH), Superoxide Dismutase (SOD) and catalase by spectrophotometry by spectrophotometry. Pro-inflammatory markers: Tumor Necrosis Factor-α (TNF-α) and Interleukin 1-β (IL-1β) were assessed using ELISA. Glial Fibrillary Acidic Protein (GFAP) and B-cell lymphoma 2 (Bcl-2) activities were also assessed by immunohistochemistry. Data were analyzed using descriptive statistics and ANOVA at α0.05. Rats given ethanol and CASA plus ethanol significantly increased in oxidative level of MDA and NO respectively. There was significant decreased in GSH, SOD and catalase level when compared with control Rats given ethanol and CASA plus ethanol showed significantly increased TNF-α while in IL-1β the result showed significantly increased in all the treated groups. Immunohistochemical results showed significantly increased GFAP-positive astrocytes in all treated groups, and Bcl-2 immunopositively cells were significantly increased in the treated groups when compared to control. Chronic and combined use of ethanol with a cocktail of caffeine and acetyl salicylic acid induced increased oxidative stress, up-regulation of pro-inflammatory cytokines, astrogliosis and apoptosis in Wistar rats.