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Advances in Pharmacological Sciences - Volume 2015 2015, Article ID 346259, 9 pages -

Research Article

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt

Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 80200, Saudi Arabia

Department of Pharmacology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia

Received 20 May 2015; Revised 2 September 2015; Accepted 14 September 2015

Academic Editor: Berend Olivier

Copyright © 2015 Mohamed Naguib Zakaria et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor RAGE, AGEs mediate oxidative stress and-or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system CNS complications in STZ-induced 50 mg-kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline performance in the Y-maze, neuronal degeneration Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.

Autor: Mohamed Naguib Zakaria, Hany M. El-Bassossy, and Waleed Barakat



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