Ramin Karimi-Sales1,2, Mehrafarin Ashiri1,2, Maryam Hafizi3, Somayeh Kalanaky3, Amir Hossein Maghsoudi3,4, Saideh Fakharzadeh3, Nader Maghsoudi5, Mohammad Hassan Nazaran6. 1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran. 3. Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran. 4. Humer Daroo, TUMS pharmaceutical incubation center, Kargar Shomali, Tehran, Iran. 5. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. nmaghsoudi@sbmu.ac.ir. 6. Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran. mnazaran@nanochelatingtechnology.com.
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-βeta (Aβ) injection into the brain. MATERIALS AND METHODS: Aβ (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 Aβ 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 Aβ (1-42)-injected groups and improving apoptosis factor in healthy mice. CONCLUSION: These results indicated that ALZc3 could significantly prevent the memory impairment and Aβ (1-42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.
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-βeta (Aβ) injection into the brain. MATERIALS AND METHODS: Aβ (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 Aβ 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 Aβ (1-42)-injected groups and improving apoptosis factor in healthy mice. CONCLUSION: These results indicated that ALZc3 could significantly prevent the memory impairment and Aβ (1-42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.
Authors: Rui E Castro; Maria M M Santos; Paulo M C Glória; Carlos J A Ribeiro; Duarte M S Ferreira; Joana M Xavier; Rui Moreira; Cecília M P Rodrigues Journal: Curr Pharm Des Date: 2010 Impact factor: 3.116
Authors: Tomasz Wasiak; Maksim Ionov; Krzysztof Nieznanski; Hanna Nieznanska; Oxana Klementieva; Maritxell Granell; Josep Cladera; Jean-Pierre Majoral; Anne Marie Caminade; Barbara Klajnert Journal: Mol Pharm Date: 2012-01-13 Impact factor: 4.939