Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 3 (2013), Issue 1, pp. 71-82 
doi:10.11131/2013/101341

Modulation of Fructose-Induced Insulin Resistance Syndrome in Rats by Rosiglitazone and α-Lipoic Acid

Increased fructose intake has been linked to the epidemiology of insulin resistance (IR) syndrome, type 2 diabetes mellitus, renal damage and non-alcoholic steatohepatitis. As oxidative stress plays a pivotal role in the pathology of IR, the present study was conducted to investigate the effects of rosiglitazone alone or combined with α-lipoic acid, a potent antioxidant, on fructose-induced IR syndrome in rats. Markers chosen for assessment included effects on body weight gain, glucose and insulin levels, IR, β- cell function, lipid profile, nitric oxide (NO) metabolites and antioxidant status. Moreover, liver and kidney functions were assessed both biochemically and histologically. Male rats were fed with fructose-enriched diet (FED) or standard rat chow for 16 weeks. By the end of the 10th week, FED-fed rats were divided into three groups; one was left untreated (control group) and the other 2 groups were treated p.o. with rosiglitazone (4 mg/kg) and rosiglitazone plus α-ℓipoic acid (100 mg/kg), respectively. Treatments continued daily for 6 weeks, afterwards blood samples were collected, animals were sacrificed and their livers and kidneys isolated. Feeding rats with FED resulted in increased weight gain, hyperinsulinemia, hyperglycemia, IR and β- cell dysfunction. These changes were coupled with disturbances in lipid homeostasis, antioxidant status and alterations in NO metabolites as well as liver and kidney dysfunctions. Concomitant administration of α-ℓipoic acid with rosiglitazone potentiated the effects of the latter on most of the investigated parameters. In conclusion, the combination of rosiglitazone and α-ℓipoic could ameliorate most of the symptoms associated with IR syndrome in rats.