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