Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer's disease; novel perspectives for an old drug

Document Type : Original Article


1 Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.

2 Department of Histology and Cell Biology, Faculty of Medicine, Assiut University, Assiut, Egypt

3 Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt

4 Pharmacology Department, Faculty of Medicine, Assiut University


Neuroinflammation plays a crucial role in Alzheimer's disease (AD) pathogenesis. Apoptosis, along with impaired neurogenesis, has been linked to AD neurodegenerative cell death, likely due to overexpression of cyclooxygenase-2 (COX-2). We investigated whether the concurrent administration of celecoxib, a selective COX-2 inhibitor, with rivastigmine, the standard anti-Alzheimer, would enhance rivastigmine anti-Alzheimer activity in the aluminum chloride (AlCl3) Alzheimer's rat model. Male rats were randomly assembled into control (Cont), AlCl3-treated (Al), rivastigmine-treated (RIVA), celecoxib-treated (Celeco), and combined rivastigmine and celecoxib-treated (RIVA+Celeco) groups. They were studied for memory, and cognitive skills, along with evaluating hippocampal acetylcholinesterase (AChE) activity. Hippocampal neuropathology, besides apoptosis, astroglial injury, and neurogenesis, were assessed through examining the expression of their related protein markers; activated caspase-3, glial fibrillary acidic protein (GFAP), and nestin. Celecoxib, rivastigmine, and their combination attenuated AlCl3-induced intellectual impairment and the associated neurodegenerative changes. However, the combination therapy had no additional neuroprotective advantage over rivastigmine alone, except for the enhancement of neurogenesis and suppression of apoptosis in the AL-intoxicated rats. As compared to rivastigmine, the efficacy of celecoxib in combination with rivastigmine confers neuroprotection only at the cellular level, enhancement of neurogenesis, and suppression of apoptosis, without having a mitigating effect on Al-induced cognitive impairment.