ABSTRACT
Aluminium metal is a very potent neurotoxin that is capable of triggering various neuroinflammatory events in the brain and these include oxidative stress, production of biomarkers of neuroinflammation, apoptosis, cognitive decline and dementia. Sources of aluminium intoxication include vaccines, drugs, water, cooking utensils, etc. The use of aluminium as an adjuvant in vaccines has been linked to autism, autoimmunity, long-term brain inflammation and associated neurological complications. Eugenol, on the other hand, is a phenolic compound that belongs to the class Phenylpropanoids and a major component of many spice-derived plants which includes clove, cinnamon, and various species of Ocimum, coffee, Banana Soya bean and beans e.t.c. All plants listed above are known to possess antioxidant or anti-inflammatory properties and these properties are postulated to be performed by eugenol. This Study is aimed at evaluating the effect of eugenol on the cerebral (layers III and V), cerebellar cortices and hippocampus (CA1 and CA3 reregions) following administration of aluminium chloride; neurobehavioural studies using Morris water maze (MWM) for learning and memory, elevated plus maze (EPM) for anxiety like-behaviour and behaviour scored includes open and close duration, rearing and grooming; forelimb grip strength test to assess muscular strength; neurochemical analysis to assess the concentration of neuro-trace elements (Magnesium Mg, Manganese Mn, Iron Fe) and brain levels of Aluminium was also assessed. Brain tissue homogenates were used to assess levels of lipid peroxidation, Malondialdehyde (MDA), antioxidant enzymes Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT); intramitochondrial accumulation of 8-Hydroxy-2-deoxyguanosine (8-OHdG), antiapoptotic (Bcl-2) and proapoptotic proteins Bax and Caspasce-3; endogenous enzymatic levels of aceylcholinestserase (AchE) and detect the presence of cholinergic neurons using ACAT-1 stains; Routine hematoxylin and eosin (H&E) stains, cresyl fast violet (CFV) for Nissl bodies, Congo red for amyloidal plaques and Golgi stains for neuronal dendritic field. A total of thirty (30) apparently healthy adult Wistar Rats of either sex with a weight of 140-160 g was divided into six (6) groups with five (5) rats in each group. Group I served as control (CTRL), groups II-VI were designated as treatment groups. Group I served as the control was administered 0.6 ml distilled water. Neurotoxicity was induced in rats by oral administration of Aluminium Chloride (AlCl3). Group II was administered 100 mg/kg AlCl3 and was designated as AC. Group III was administered 300 mg/kg Eugenol and 100 mg/kg AlCl3 and was designated as EGH+AC; Group IV was administered 150 mg/kg Eugenol and 100 mg/kg AlCl3 and was designated as EGL+AC; Group V was administered 300 mg/kg Eugenol only and designated as EGH; Group VI was administered 150 mg/kg Eugenol only and designated as EGL. Eugenol was administered orally throughout the duration of this study for 21 days. On day 22 rats were euthanized using 0.8 ml of ketamine. Results revealed that exposure to AlCl3 resulted in neurotoxicity in rats which were evident from Morphological, histometric, histologic, and histochemical alterations or changes in the brain; AlCl3 resulted in an increase in anxiety like behaviour, cognitive impairments and motor deficits in the neurobehavioural assessment; significant (p<0.05) alterations in the levels of neurotrace elements; significant (p<0.05) increase in MDA levels, significant (p<0.05) reduction in antioxidant (SOD, CAT, GPx) enzyme activity, significant (p<0.05) increase in the level of 8-OHDG, proapoptotic protein (Bax, Caspasce-3) and endogenous acetlycholinesterase (AchE). Co-administration of Eugenol and AlCl3 resulted in preserved histologic and histochemical alterations in the cerebral, cerebellar and hippocampal regions (CA1 and CA3) relative to the control; ameliorated anxiety like responses, prevented cognitive deficits produced by AlCl3 relative to the control; alterations in the concentrations of neurotrace metals (Mg, Mn and Fe); prevented alterations in the levels of biomarkers of lipid peroxidation (MDA), antioxidant enzymes (SOD, GPx and CAT) and endogenous acetylcholinesterase (AchE) activity. The result obtained from this study revealed that eugenol can protect the cerebral (Layers III and V), cerebellar cortices and hippocampus from pathological changes associated with oral administration of AlCl3. The protective properties of eugenol is due to its free radical scavenging property by maintaining the appropriate level of both enzymatic and non-enzymatic fortification in opposition to AlCl3 induced neurotoxicity. Results obtained revealed that eugenol is an effective treatment in attenuating the deleterious effects of AlCl3 induced neurotoxicity.