Background: Metabolic syndrome (MS) is associated with chronic hyperglycemia, which leads to formation of advanced glycation end products (AGEs) that involved in the disease pathogenesis. MS is also accompanied by mineralocorticoid receptor (MR) activation, which has deleterious metabolic effects. The present study was designed to compare the effect of alagebrium (ALA), standard AGEs cross link breaker, and spironolactone (SPL), MR antagonist, on MS induced by high carbohydrate and high fat diet (HCFD).
Methods: 32 rats divided into: normal control group (8 rats) fed standard diet, and MS group (24 rats) received HCFD for 10 weeks, after which they were divided into 3 equal subgroups and continued on HCFD for further 6 weeks and served as: MS control, ALA treated (10 mg/kg/day), and SPL treated (50 mg/kg/day). Studied parameters were mean arterial blood pressure (MABP), body weight (BW), fasting blood glucose (FBG), serum insulin, HbA1c, plasma lipids, liver enzymes, oxidative stress & inflammatory markers, and liver histopathology.
Results: HCFD produced MS as evidenced by significant deleterious effect on all parameters, and treatment with either ALA or SPL produced significant favorable effect on these parameters. In comparison, ALA was superior in decreasing FBG, HbA1c, serum TGs, ALT, GGT and hepatic inflammatory markers. SPL was superior in decreasing MABP, BW, serum insulin, LDL, and antioxidant status.
Conclusion: ALA and SPL showed protective effect on dietary induced MS, both could be promising in management of the disease.
Keywords: Alagebrium, Spironolactone, metabolic syndrome.