PPAR-gamma agonists: antioxidant and metabolic effects in fructose induced insulin resistant rats

ABSTRACT

The aim of the present study was to investigate oxidative stress in fructose induced model of insulin resistance in albino rats via measuring plasma superoxide dismutase enzyme [SOD enzyme]. Additionally, the present work compared the effects of two different insulin sensitizers, pioglitazone and rosiglitazone, on plasma glucose, plasma insulin, SOD enzyme, lipid profile, blood pressure and vascular reactivity in fructose induced model of insulin resistance in albino rats. The results revealed 20.38%* reduction of the superoxide dismutase enzyme in insulin resistant rats compared with the control. However, after giving PPAR-y agonists, pioglitazone and Rosiglitazone for 4 weeks, there was significant rise in SOD enzyme by 44.6 l%* in the former group compared to the latter, where there was significant rise by only 32.21%*. These PPAR-y agonists, also showed significant improvement in glycemic control, insulin resistance index, systolic blood pressure and specially lipid profile. The results of the present work indicate that these two agents have a promising place in the treatment of insulin resistance syndrome in humans not only due to their metabolic effects, but also due to their antioxidant action. In vitro experiments also revealed that pretreatment with pioglitazone and rosiglitazone were associated with blunting in aortic ring contractile response towards phenylephrine and enhanced endothelial dependent relaxation response to acetylcholine, compared to insulin resistant untreated group. Both drugs produced significant increase of effective concentration 50 [EC50] of phenylephrine by 60.7%* and 32.4%* respectively. Similarly, both drugs produced significant increase acetylcholine induced relaxation by 549%* and 40.8%* respectively when compared to insulin resistant group. However, pioglitazone proved to be more potent. These results are in accordance with the lowering of elevated systolic blood pressure in vivo experiments produced by both drugs