The current study aimed to assess and compare the preventive effects of carvedilol (CAR) and donepezil (DONP) on aluminum chloride (AlCl3)-induced Alzheimer's Disease (AD). A total of 40 male adult Wistar rats were allocated into four groups at random (10 rats each). Saline was given to the control group intraperitoneally (i.p) for six weeks. The second group received saline for two successive weeks followed by 70 mg/kg/day AlCl3 i.p. for four successive weeks. The third group received 1 mg/kg CAR i.p. for two sequential weeks, followed by CAR and AlCl3 concurrently for four weeks. The fourth group received DONP 0.75 mg/kg i.p. alone for two successive weeks, followed by DONP and AlCl3 simultaneously for a further four weeks. AlCl3 administration demonstrated a marked discrepancy in learning and memory indicated by a deficit in behavioral tests, elevation of serum and brain nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), aluminum (Al), acetylcholinesterase (AChE), and amyloid-beta (Aβ) (1-42) protein levels.
On the other hand, AlCl3 administration significantly reduced superoxide dismutase (SOD) and catalase (CAT) activities compared to the control group. However, treating rats with CAR or DONP concurrently with AlCl3 produced significant amelioration of behavioral test measurements, accompanied by a significant improvement in biochemical parameters. In addition, histopathological changes confirmed the behavioral and biochemical results. Moreover, CAR produced significant effects compared to DONP. The present study suggests that CAR protects against AlCl3-induced cognitive dysfunction through its anti-inflammatory, antioxidant, and protective effects against Aβ in a rat model of Alzheimer's disease.