Antioxidant Effect of Atorvastatin in Type 2 Diabetic Patients


Evidence has long been existed regarding the relationship between oxidative stress and diabetes. The present study was conducted to assess the effect of atorvastatin on selected oxidative stress parameters and its effect on lipid profile parameters in dyslipidaemic type 2 diabetic patients. Fifty nine dyslipidaemic type 2 diabetic patients were included in this study. A full history was taken and general examination was performed. The patients were taking an oral hypoglycaemic drug (glibenclamide) during the study. The patients were followed up for 60 days and divided randomly into 2 groups. Group I (n = 31) received no drug and served as dyslipidaemic diabetic control. Group II (n = 28) received atorvastatin tablets 20 mg once daily at night. Blood samples were drawn from the patients at the beginning and after 60 days of follow up between 8:30 and 10:30 am after at least 12-14 hours fasting. Fasting blood glucose, lipid profile, selective oxidative stress parameters, glutathione S reductase (GSH), malondialdehyde (MDA) levels, glutathione S transferase (GST) and catalase (CAT) activities were measured. Renal and hepatic functions were also assessed. The results showed that atorvastatin treatment produced significant increase in serum levels of GSH and High Density Lipoprotein (HDL), while serum levels of MDA, Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C) and Very Low Density Lipoprotein (VLDL) were significantly decreased. However, no significant effect was observed regarding CAT and GST activity. There were insignificant correlations between atorvastatin induced changes in the oxidation markers and the observed changes of the lipid profile. In conclusion, the antioxidant effect of atorvastatin could be unrelated to its hypolipidemic action as there was insignificant correlation between changes in lipid profile and oxidative stress in this study.

Share and Cite:

Hadi, N. , Abdelhussein, M. , Alhamami, O. , Rudha, A. and Sabah, E. (2010) Antioxidant Effect of Atorvastatin in Type 2 Diabetic Patients. Pharmacology & Pharmacy, 1, 53-59. doi: 10.4236/pp.2010.12008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] D. J. Betteridge, “What is Oxidative Stress?” Metabolism, Vol. 49, No.2, 2000, pp. 3-8.
[2] B. Halliwell, “Free radicals, Antioxidants & Human Disease: Curiosity, Cause or Consequence,” Lancet, Vol. 344, No. 8924, 1994, pp. 721-724.
[3] K. Kannan and S. K. Jain, “Oxidative Stress & Apoptosis,” Pathophysiology, Vol. 7, No. 3, 2000, pp. 153-163.
[4] S. Shah, M. Iqbal, J. Karam, M. Salifu and S. I. Mcfarlane, “Oxidative stress, Glucose Metabolism & the Prevention of Ttype 2 Diabetes: Pathophyiological Insights,” Antioxidants & Rredox Signaling, Vol. 9, No. 7, 2007, pp. 911-929.
[5] I. S. Young and J. V. Woodside, “Antioxidants in Health & Disease,” Journal of Clinical Pathology, Vol. 54, No. 3, 2001, pp. 176-186.
[6] J. A. Florence and B. F Yeager, “Treatment of Type 2 Diabetes Mellitus,” American Family Physician, Vol. 59, 1999, p. 10.
[7] J. L. Mehta, N. Rasouli, A. K. Sinha and B. Molavi, “Oxidative Stress in Diabetes: A mechanistic Overview of its Effects on Atherogenesis and Myocardial Dysfunction,” The International Journal of Biochemistry & Cell Biology, Vol. 38, No. 5-6, June 2006, pp. 794-803.
[8] L. W. Oberley, “Free Radicals and Diabetes,” Free Radical Biology & Medicine, Vol. 5, No. 2, 1988, pp. 113- 124.
[9] N. Eisei and T. Hirokazu, “Parameters for Measurement of Oxidative Stress in Diabetes Mellitus: Applicability of ELISA for Clinical Evaluation,” Jòurnal of Investigation Medicine, Vol. 53, No.4, May 2005, pp. 167-175.
[10] J. S. Johansen, A. K. Harris, D. J. Rychly and A. Ergul, “Oxidative Stress & the Use of Antioxidants in Diabetes: Linking Basic Science to Clinical Practice,” Cardiovascular Diabetology, Vol. 4, April 2005, p. 5.
[11] J. Patel, “Dyslipidaemia in Diabetes,” British Midical Journal Clinical Evidence, Vol. 8, No. 4, 2006, pp. 355- 364.
[12] C. M. Florkowski, “Management of Co-Existing Diabetes Mellitus & Dyslipidaemia: Defining the Role of Thiazolidinediones,” American Journal of Cardiovascular Drugs, Vol. 2, No. 1, 2002, pp. 15-21.
[13] F. Violi, L. Loffredo, L. Musella and A. Marcoccia, “Should Antioxidant Status be Considered in Interventional Trials with Antioxidants?” Heart, Vol. 90, No. 6, 2004, pp. 598-602.
[14] M. C. Sheffield, “Multiple Effects of Statins in Non Lipid Disease States,” US Pharmacist, Vol. 6, 2004, pp. 38-54.
[15] J. K. Liao, “Isoprenoids as Mediators of the Biological Effects of Statins,” Journal Clinical Investigation, Vol. 110, No. 3, August 2002, pp. 285-288.
[16] F. R. Danesh and Y. S. Kanwar, “Modulatory Effects of HMG-CoA Reductase Inhibitors in Diabetic Microangiopathy,” The FASEB Journal, Vol. 18, No. 7, 2004, pp. 805-815.
[17] J. Beltowski, “Statins & Modulation of Oxidative Stress,” Toxicology Mechanisms & Methods, Vol. 15, No. 2, 2005, pp. 61-92.
[18] B. B. Hodgson and R. J. Kizior, “Saunders Nursing Drug Handbook,” Jones and Bartlett, Boston, 2003.
[19] A. Heerey, M. Barry, M. Ryan and A. Kelly, “The Potential for Drug Interactions with Statin Therapy in Iraland,” Irish Journal of Medical Science, Vol. 169, No. 3, 2001, pp. 176-179.
[20] A. J. Ellsworth, D. M. Witt, D. C. Dugdale and L. M. Oliver, “Mosby,s Medical Drug Reference,” 2003.
[21] R. S. Munford, “Statins & the Acute Phase Response,” New England Journal of Medicine, Vol. 344, No. 26, June 2001, pp. 2016-2018.
[22] M. H. Shishehbor, M. L. Brennan, R. J. Aviles, X. Fu, M. S. Penn, D. L. Sprecher and S. L. Hazen, “Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory pathways,” Circulation, Vol. 108, No. 4, 2003, pp. 426-431.
[23] T. Vishal, G. Bano, V. Khajuria, A. Parihar and S. Gupta, “Pleiotropic Effects of Statins,” Indian Journal Pharmacology, Vol. 37, No. 2, 2005, pp. 77-85.
[24] M. E. Marketou, E. A. Zacharis, D. Nikitovic, E. S. Ganotakis, F. I. Parthenakis and N. Maliaraki, “Early Effects of Simvastatin Versus Atorvastatin on Oxidative Stress Proinflammatory Cytokines in Hyperlipidaemic Subjects,” Angiology, Vol. 57, No. 2, March 2006, pp. 211-218.
[25] V. V. Uzunova, A. N. Tolekova, G. S. IIieva and A. P. Trifonova, “Renin-Angiotensin System & Lipid Peroxidation,” Bulgarian Journal of Veterinary Medicine, Vol. 1, 2005, pp. 69-75.
[26] B. I. Kasiske, J. Z. Ma, R. S. Kalil and T. A Louis, “Effects of Antihypertensive Therapy on serum lipids,” Annals of Internal Medicine, Vol. 122, No. 2, January 1995, pp. 133-141.
[27] N. Kebapci, B. Efe, F. Akyuz, E. Sunal and C. Demirustu, “Oxidative Stress & Antioxidant Therapy in Type 2 Diabetes Mellitus,” Turkish Journal of Endocrinology & Metabolism, Vol. 4, 1999, pp. 153-162.
[28] G. L. Ellman, “Tissue Sulfhydyl Groups,” Archives of Biochemistry and Biophys, Vol. 82, No. 1, May 1959, pp. 70-77.
[29] B. Guidet and S. V. Shah, American Journal of Physiology, Vol. 257, No. 26, 1989, p. 440.
[30] W. H. Michael, M. J. Pabst and W. B. Jakoby, “Glutathione-S-Transferase. The First Enzymatic Step in Mercapturic Acid Formation,” Journal of Biological Chemistry, Vol. 22, No. 25, 1974, pp. 7130-7139.
[31] H. Aebi, In Methods of Enzymatic Analysis, H.U. Bergme-tered, ed, New York, Academic press 1974, Vol, 2, pp. 674-678.
[32] W.T. Friedewald, R.I. Levy and D.S. Fredrickson, “Estimation of the Concentration of LDL-C in Plasma without Use the Preparative Ultracentrifuge,” Clinical Chemistry, Vol. 18, No. 6, Jun 1972, 499-502.
[33] V. Save, N. Patil, N, Moulik and G. Rajadhyaksha, “Effect of Atorvastatin on Type 2 Diabetic Dyslipidaemia,” Journal of Cardiovascular Pharmacololgy & Therapeutics, Vol. 11, No. 4, December 2006, pp. 262-270.
[34] M. Koter, M. Broncel, J. Chjnowska-Jezierska, K. Klikczynska and I. Franiak, “The Effect of Atorvastatin on Erythrocyte Membranes & Serum Lipids in Patients with Type 2 Hypercholesterolaemia,” European Journal of Clinical Pharmacology, Vol. 58, No. 8, 2002, pp. 501-506.
[35] J.K. Liao and U. Laufs, “Pleiotropic Effects of Statins,” Annual Review Pharmacology & Toxicology, Vol. 45, Febreuary 2005, pp. 89-118.
[36] J. C. Mason, “Statins & Their Role in Vascular Protection,” Clinical Science, Vol. 105, 2003, pp. 251-266.
[37] S. Passi, A. Stancato, E. Aleo, A. Dmitrieva and G.P. Littarru, “Statins Lower Plasma & Lymphocyte Ubiquinol Ubiquinone Without Affecting Other Antioxidants & PUFA,” Biofactors, Vol. 18, No. 1-4, 2003, 113-124.
[38] S. Wassmann, U. Laufs, K. Muller, C. Konkol, K. Ahlbory and .T. Baumer, et al, “Cellular Antioxidant Effects of Atorvastatin in Vitro & in Vivo,” Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 22, 2002, pp. 300-305.
[39] DALI Study Group, “The Effect of Aggressive Versus Standard Lipid Lowering by Atorvastatin on Diabetic Dyslipidaemia: the DALI Study: A double Blind Randomized Placeb Controlled Trial in Patients with Type 2 Diabetes & Diabetic Dyslipidaemia,” Diabetes Care,Vol. 24, No. 8, 2001, pp. 1335-1341.
[40] M. Alegret and J.S. Silvestre, “Pleiotropic Effects of Statins & Related Pharmacological Experimental Approaches,” Methods and Finding Experimental Clinical Pharmacology, Vol. 28, No.9, 2006, pp. 627.
[41] K. Sakabe, N. Fukuda, K. Wakayama, T. Nada, H. Shinohara and Y. Tamura “Effects of Atorvastatin Therapy on the Low - Density Lipoprotein Subfraction, Remnant-Like Particles Cholesterol, and Oxidized Low-Density Lipoprotein within 2 Weeks in Hypercholesterolemic Patients,” Circulation Journal, Vol. 67, No. 10, 2003, pp. 866-870.
[42] U. Laufs and J.K. Liao, “Isoprenoid Metabolism & the Pleiotropic Effects of Statins,” Current Atherosclerosis Reports, Vol. 5, No.5, 2003, pp. 372-378.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.