EFFECT OF CO-ADMINISTRATION OF QUERCETIN AND DONEPEZIL ON INFLAMMATORY CYTOKINES, ANTIOXIDANT AND PANCREATIC HISTOMORPHOLOGY IN ALUMINIUM CHLORIDE-INDUCED TOXICITY IN RAT

ABSTRACT There is arising the complications as a result of exposure to aluminum chloride through many ways, and there is a need for a solution to this effect, quercetin and donepezil has been reported to have a neuroprotective and cognitive effect. This study effect of quercetin and donepezil on antioxidant status and pancreatic histomorphology in aluminiumchloride-induced toxicity in rats. Thirty (70) healthy females Wistar rats weighing between 120-150g were randomly assigned into five groups (A-F) of 5 animals each (10 rats/group). A total of seventy female rats weighing 120-150g (Rattusnovergicus) were randomly assignedinto six groups (n=10 each). Group A were fed standard rat chow and 10mls/kg Normal Saline for28 days; Group B were fed standard rat chow for 28 days and 100 mg/kg AlCl3 only for 14 days,Group C were fed standard rat chow 200 mg/kg of dietary quercetin supplement for 14 days. GroupD, were fed standard rat chow for 28 days and 3 mg/kg AlCl3 only for 14 days; Group E were fedstandard rat chow, 100 mg/kg of AlCl3 and 3 mg/kg of Donepezil for 14 days while group F werefed standard rat chow 200 mg/kg of dietary quercetin supplement and 100 mg/kg of AlCl3 for 14days; Group G were fed standard rat chow 200 mg/kg of dietary quercetin supplement for 14 days,100 mg/kg of AlCl3, 3 mg/kg of Donepezil. Drugs were administrated orally by gavage and dosagewas based on body weight of each animal. At the end of the experimental periodAt the end of the experimental period animals were sacrificed by cervical dislocation. The pancreas was dissected out, observed grossly, weighed and fixed in 10% formol saline. Sections of the pancreas were processed for paraffin-embedding, cut at 5 µm and stained with haematoxylin and eosin for general histological study. The result from the body weight of this study showed a decrease in body weight in group D whilethe weight loss was ameliorated in groups F, G, and H.The feed intake result from this study is decreased with groups B and F compared to A, while itsignificantly increased in group G and H. The time spent in the open are decreased with group Dcompared to group A while the also increased with groups E, F, G and H. The percentagealternation decreased with group B compared to A while it increased with groups E,F G and H. The histological findings from this study showed degenerating neuronal cells in group D,compared to group A, however, the integrity of the dentate gyrus was maintained in groups E, F, G and H compared to group D. Total antioxidant capacity (TAC) increased significantly with group B,E,F and G while it decreased in group D compared to the normal group which indicate that it is prone to oxidative stress and damage. Malondialdehyde (MDA) levels increased significantly with groups D, and F compared to normal control group, MDA levels decreased with groups B and G which indicate that they are prone to lipid leakage and oxidative stress. Regarding inflammatory cytokines, there is an increase in the level of pro-inflammatory cytokines (IL-1beta)in group D and E compare to the normal control group, Additionally,the levels of anti-inflammatory cytokines increased in group G compared to group A. The histological findings showed that AlCl3 administration was associated with karyolysis, cytoplasmic vacuolization and pyknosis as revealed in the group C and D, while it was almost restored to the normal in the groups E, F and D. This studies has shown, explore and provide information on how the combined administration of quercetin and donepezil affects inflammatory cytokines, antioxidant status, and the histomorphology of the pancreas in rats with toxicity induced by aluminium chloride.