Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Objective: Incidence of metabolic syndrome (MS) is strongly associated with increased fructose consumption. This study aimed to elucidate the role of pioglitazone, Ü-lipoic acid, hesperidin, caffeic acid and their combinations on fructose-induced MS. Materials and methods: Theriteen groups of rats (n=8) were used. Groups 1-5 were fed on normal diet. First group served as normal control, and the remaining received pioglitazone (2.7 mg/kg), Ü-lipoic acid (100 mg/kg), hesperidin (50 mg/kg) and caffeic acid (20 mg/kg), respectively. Groups 6-13 were fed on fructose-enriched diet (FED) for 15 weeks. The 6th group served as positive control group, and the remaining groups received pioglitazone (2.7 mg/kg), Ü-lipoic acid (100 mg/kg), combination of pioglitazone and Ü-lipoic acid, hesperidin (50 mg/kg), combination of pioglitazone and hesperidin, caffeic acid (20 mg/kg) and combination of pioglitazone and caffeic acid, respectively. Treatments started 10 weeks after the beginning of fructose feeding. At the end of the study, blood and tissue samples were collected for estimation of MS-related markers. Results: Induction of MS was associated with increased weight gain and insulin resistance coupled with elevated levels of blood glucose, insulin, uric acid, urea, creatinine and lipids as well as activities of liver transaminases. FED also reduced glutathione peroxidase activity and total antioxidant capacity, increased nitric oxide and lipid peroxides contents parallel to increased serum levels of leptin and tumor necrosis factor-alpha. Treatment with pioglitazone, Ü-lipoic acid, hesperidin or caffeic acid attenuated most of the changes associated with MS. Besides, combinations of pioglitazone with any of tested agents further improved disease markers

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