Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Pharmacology

Introduction: Metabolic syndrome is a cluster of metabolic risk factors that promote the development of diabetes and cardiovascular disease.Recent epidemiological studies have linked the prevalence of metabolic syndrome with increasing serum uric acid levels. Elevated serum uric acid level occurring with metabolic syndrome may not only be a consequence of hyperinsulinemia, but also it promotes and aggravates the pathogenesis of metabolic syndrome either directly or due to oxidative stress. We attempt to elucidate the role of uric acid in metabolic syndrome and the role of uric acid lowering agents: allopurinol, febuxostat and both drug combinations to ameliorate manifestations of metabolic syndrome. Materials and Method: After induction of metabolic syndrome in male Sprague Dawley albino rats using high fructose diet for 8 weeks, allopurinol, febuxostat and both drug combinations were given orally for 4 weeks at a dose (20mg/kg/day) and (5mg/kg/day) respectively. Systolic blood pressure was measured non-invasively using a rat tail sphygmomanometer. The body weight was taken on weekly basis using the electronic weighing scale. Blood samples were collected for estimation of serum levels of different metabolic parameters. In vitro study on the aortic vascular integrity was performed Result: The current study revealed that hyperuricemia contributes to development of metabolic syndrome. Urate lowering agents showed remarkable improvement in features of metabolic syndrome and this improvement is secondary to reduction in the serum uric acid levels. Conclusion: A significant difference was observed between allopurinol , febuxostat and both drug combinations on lowering the serum uric acid level , markers of oxidative stress and fasting hyperglycemia but there was no great difference between them in management of other features of the syndrome

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