Neuroprotective Effect of New Nanochelating-Based Nano Complex, ALZc3, Against Aß (1-42)-Induced Toxicity in Rat: a Comparison with Memantine.

ABSTRACT

PURPOSE: The current drugs for Alzheimer's disease (AD) are only used to slow or delay the progression of the pathology. So using a novel technology is a necessity to synthesize more effective medications to control this most common cause of dementia. In this study, using nanochelating technology, ALZc3 was synthesized and its therapeutic effects were evaluated in comparison with memantine on a well-known rat model of AD, which is based on Amyloid-ßeta (Aß) injection into the brain. MATERIALS AND METHODS: Aß (1-42) was injected bilaterally into the CA1 area of the hippocampus of male rats and then animals were treated daily by oral administration of Alz-C3, memantine or their vehicles. Activities of antioxidant enzymes catalase and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels, as well as Bax/Bcl-2 ratio, caspase-3 activation, and TNF-α expression were evaluated 7 days after Aß injection. Finally, learning and memory of the rats were assessed by Morris water maze test. RESULTS: ALZc3 and memantine improved memory impairment and antioxidant activity and reduced TNF-α expression, caspase-3 activity and Bax/Bcl-2 ratio in the rat's hippocampus. The results showed a superiority of ALZC3 compared to memantine in reducing caspase-3, increasing CAT activity in Aß (1-42)-injected groups and improving apoptosis factor in healthy mice. CONCLUSION: These results indicated that ALZc3 could significantly prevent the memory impairment and Aß (1-42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.