Combined Therapy of Pioglitazone and Atorvastatin Alleviate Diabetes in Rats More Effectively than That of Mono Therapy


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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Ali, H. , Rahman, A. , Islam, S. , Mamun, A. , Zannah, S. , Khurshid Alam, A. , Rahman, A. and Rashid, M. (2014) Combined Therapy of Pioglitazone and Atorvastatin Alleviate Diabetes in Rats More Effectively than That of Mono Therapy. Pharmacology & Pharmacy, 5, 504-513. doi: 10.4236/pp.2014.55060.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Sharma, V.K., Kumar, S., Patel, H.J., et al. (2010) Hypoglycemic Activity of Ficus Glomerata in Alloxan Induced Diabetic Rats. International Journal of Pharmaceutical Sciences Review and Research, 1, 18-22.
[2] World Health Organization (2011) Global Status Report on Noncommunicable Diseases 2010. World Health Organization, Geneva.
[3] Wild, S., Roglic, G., Green, A., et al. (2004) Global Prevalence of Diabetes: Estimates for 2000 and Projections for 2030. Diabetes Care, 27, 1047-1053.
[4] Kumar, P. and Clark, M. (2002) Diabetes Mellitus and Other Disorders of Metabolism. In: Sunders, W.B., Ed., Clinical Medicine, Vol. 2, Elsevier, London, 1069-1071.
[5] Amira, A.M.A. (2010) Oxidative Stress and Disease: An Update Review. Research Journal of Immunology, 3, 129-145.
[6] Vijaya, L.S.V., Padmaja, G., Periannan, K., et al. (2009) Oxidative Stress in Cardiovascular Disease. Indian Journal of Biochemistry and Biophysics, 46, 421-440.
[7] Hsieh, C.C., Yen, M.H., Yen, C.H., et al. (2001) Oxidised Low Density Lipoprotein Induce Apoptosis via Generation of Reactive Oxygen Species in Vascular Smooth Muscle Cells. Cardiovascular Research, 49, 135-145.
[8] Phan, S.H., Gannon, D.E., Varani, J., et al. (1989) Xanthine Oxidase Activity in Rat Pulmonary Artery Endothelial Cells and Its Alteration by Activated Neutrophils. The American Journal of Pathology, 134, 1201-1211.
[9] Akihiro, M., Yoshitaka, H., Hiroaki, S., et al. (2001) Possible Involvement of Rho-Kinase in the Pathogenesis of Hypertension in Humans. Hypertension, 38, 1307-1310.
[10] Malviya, N., Jain, S. and Malvia, S. (2010) Antidiabetic Potential of Medicinal Plants. Acta Poloniae Pharmaceutica, 67, 113-138.
[11] Matafome, P., Louro, T., Rodriques, L., et al. (2011) Metformin and Atorvastatin Combination Further Protect the Liver in Type 2 Diabetes with Hyperlipidaemia. Diabetes/metabolism Research and Reviews, 27, 54-62.
[12] Pieroni, A., Nebel, S., Quave, C., et al. (2002) Ethnopharmacology of Liakra: Traditional Weedy Vegetables of the Arbëreshë of the Vulture Area in Southern Italy. Journal of Ethnopharmacology, 81, 165-185.
[13] Yates, S.W. (2004) Comparative Effects of Available Thiazolidinediones: A Review of the Literature. P&T, 29, 584-588.
[14] Grundy, S.M. (1988) HMG-CoA Reductase Inhibitors for Treatment of Hypercholesterolemia. New England Journal of Medicine, 319, 24-33.
[15] Blois, M.S. (1958) Antioxidant Determinations by the Use of a Stable Free Radical. Nature, 181, 1199-1200.
[16] Sinha, A.K. (1972) Colorimetric Assay of Catalase. Analytical Biochemistry, 47, 389-394.
[17] Misra, H.P. and Fridovich, I. (1972) The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. Journal of Biological Chemistry, 247, 3170-3175.
[18] Albajali, A.A., Nagi, A.H., Shahzad, M., et al. (2011) Effect of Allium Sativa L. on Pancreatic Β Cells in Comparison to Nigella Sativa L. in Streptozotocin Induced Diabetic Rats. Journal of Medicinal Plants Research, 5, 5779-5784.
[19] Higashi, M., Shimokawa, H., Hattori, T., et al. (2003) Long-Term Inhibition of Rho-Kinase Suppresses Angiotensin II-Induced Cardiovascular Hypertrophy in Rats in Vivo: Effect on Endothelial NAD(P)H Oxidase System. Circulation Research, 93, 767-775.
[20] (2004) Source: “Diabetes Action Now.” An initiative of the World Health Organization and the International Diabetic Federation. WHO, Geneva, IDF, Brussels, 1-20.
[21] Balasubramanian, R., Varadharajan, S., Kathale, A., et al. (2008) Assessment of the Efficacy and Tolerability of a Fixed Dose Combination of Atorvastatin 10 mg + Metformin SR 500 mg in Diabetic Dyslipidaemia in Adult Indian Patients. Journal of the Indian Medical Association, 106, 464-467.
[22] Babu, V., Gangadevi, T. and Subramanium, A. (2002) Antihyperglycemic Activity of Cassia kleinii Leaf Extract in Glucose Feed Normal Rats and Alloxan Induced Diabetic Rats. Indian Journal of Pharmacology, 34, 409-415.
[23] Trivedi, N.A., Mazumdar, B., Bhatt, J.D., et al. (2004) Effect of Shilajit on Blood Glucose and Lipid Profile in Alloxan Induced Diabetic Rats. Indian Journal of Pharmacology, 36, 373-376.
[24] Jenkins, D.J.A., Jenkins, A.I., Wolever, T.M.S., et al. (1995) Effect of Reduced Rat of Carbohydrate Absorption on Carbohydrate and Lipid Metabolism. European Journal of Clinical Nutrition, 49, 68-73.
[25] Iams, S.G. and Wexler, B.C. (1977) Alloxan Diabetes in Spontaneously Hypertensive Rats: Gravimetric, Metabolic and Histopathological Alterations. British Journal of Experimental Pathology, 58, 177-199.
[26] Riyad, A., Abdul, G.A.S. and Suleiman, S.M. (1988) Effect of Fenugreek and Lupine Seeds on the Development of Experimental Diabetes in Rats. Planta Medica, 54, 286-290.
[27] Sharma, S.R., Dwivedi, S.K. and Swarup, D. (1996) Hypoglycaemic and Hypolipidaemic Effects of Cinnamomum Tamala Nees Leaves. Indian Journal of Experimental Biology, 34, 372-374.
[28] Munzel, T., Gori, T., Bruno, R.M. and Taddei, S. (2010) Is Oxidative Stress a Therapeutic Target in Cardiovascular Disease? European Heart Journal, 31, 2741-2749.
[29] Patel, T.B., Patel, L.D., Patel, T.B., et al. (2010) Effects of Atorvastatin as Antioxidants in Diabetic Associated Cardiovascular Complications. Journal of Pharmaceutical Sciences and Research, 2, 247-256.
[30] Campbell, I.W. (2006) The Role of Metformin and Pioglitazone in Early Combination Treatment: TZDs and Beta-Cell Preservation. British Journal of Diabetes and Vascular Disease, 6, 207-215.
[31] Tsutsui, H., Kinugawa, S., Matsushima, S., et al. (2011) Oxidative Stress in Cardiac and Skeletal Muscle Dysfunction Associated with Diabetes Mellitus. Journal of Clinical Biochemistry and Nutrition, 48, 68-71.

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