Present research was designated to investigate the hypoglycemic, hypolipidemic and antioxidant activity of the combination of pioglitazone and atorvastatin on long-term alloxan-induced diabetes rats (AIDRs). The experiments were carried out to determine blood glucose level, lipid profile, free radial scavenging activities, superoxide dismutase (SOD) and catalase in liver tissue. In addition, left ventricular (LV) hypertrophy and cardiomyocyte size were also determined by histological analysis. It was found that in short-term induction, pioglitazone significantly reduced the blood glucose level without having any considerable effect on lipid profile and antioxidant enzymes (SOD and catalase) in rats. On the other hand, atorvastatin significantly reduced total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) with marked increase in the level of high density lipoprotein cholesterol (HDL-C) and improved activity of SOD and catalase enzymes. However, pathological changes of heart and pancreas were not observed after short-term exposure to alloxan in rats. Long-term diabetes induction resulted in LV hypertrophy and prominent shrinkage of islets of Langerhans cells. Treatment with atorvastatin in combination with pioglitazone significantly reduced the LV hypertrophy, TC, TG and LDL level whereas they noticeably increased HDL level, DPPH (1,1-Diphenyl-2-picryl-hydrazyl) free radical scavenging activity, SOD and catalase activity with satisfactory recovery of Langerhans cells. The result demonstrated that combination therapy was more effective than that of mono-therapy for preventing diabetes with cardiovascular diseases (CVD) in rats.
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