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Pharm Sci. 2020;26(1): 13-24.
doi: 10.34172/PS.2019.66

Scopus ID: 85084590472
  Abstract View: 139
  PDF Download: 151

Research Article

Alagebrium Mitigates Metabolic Insults in High Carbohydrate and High Fat Diet Fed Wistar Rats

Seba Hassan 1 * ORCID logo, Ali Abdelrahman Moustafa 1, Soad Lotfy Kabil 1, Nevertyty M Mahmoud 1

1 Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Abstract

Background: Metabolic syndrome (MS) is characterized by sustained hyperglycemia that triggers advanced glycation end products (AGEs) generation. Alagebrium (ALA) is an advanced glycation end products (AGEs) cross-links breaker.

Methods: 32 Wistar rats were divided into normal control (NC) group (8 rats) and MS groups (24 rats) received a high carbohydrate high fat diet (HCFD) for 10 weeks. Rats with established MS were equally divided into 3 subgroups remained on HCFD for further 6 weeks: MS control (MSC), ALA treated received 10 mg/kg/day ALA orally and metformin treated (MF) (a reference drug) received 50 mg/kg/day MF orally. The studied parameters were systolic blood pressure (SBP), body and liver weights (BW, LW), LW/BW% ratio, fasting blood glucose (FBG), serum insulin, lipid profile, liver enzymes, serum AGEs, hepatic Interleukin-17 (IL-17), adipokines, pAkt/Akt ratio, and liver histopathology.

Results: HCFD elevated SBP, BW, LW and LW/BW% ratio, FBG, serum insulin, and AGEs. It also deteriorated lipid profile and liver enzymes, induced inflammation, insulin resistance and histopathological derangements. ALA ameliorated the elevated SBP, FBG, lipid profile, liver enzymes, mitigated insulin resistance, hepatic IL-17, serum AGEs, modulated adipokines levels and improved liver histopathology. However, MF had better effects than ALA in all studied parameters except AGEs.

Conclusion: ALA is protective against dietary-induced MS via ameliorating the inflammatory process and serum AGEs that implicated in MS pathogenesis, which makes it a promising new tool in MS treatment.

Keywords: Advanced Glycation End Products, Alagebrium, Metabolic syndrome, Metformin
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Submitted: 09 Sep 2019
Revision: 14 Nov 2019
Accepted: 11 Oct 2019
ePublished: 10 Mar 2020
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