Received: 6 June 2018 | Revised: 1 November 2018 | Accepted: 3 January 2019 DOI: 10.1002/jbt.22295 Protective effect of atorvastatin on oxidative stress in streptozotocin‐induced diabetic rats independently their lipid‐lowering effects Göknur Aktay 1 | Şule Öner Gürsoy 1 | Umut Uyumlu 1 | Songül Ünüvar 2 | Nevin İlhan 3 1 Department of Pharmacology, Faculty of Pharmacy, İnönü University, Malatya, Turkey 2 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İnönü University, Malatya, Turkey 3 Department of Biochemistry, Faculty of Medicine, Fırat University, Elazığ, Turkey Correspondence Songül Ünüvar, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İnönü University, Malatya, Turkey. Email: songul.unuvar@inonu.edu.tr Funding information Inönü University Scientific Research Projects Department, Grant/Award Number: 2011/68 Abstract In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)‐induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high‐density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non‐protein associated sulfhydryl (NP‐SH), total sulfhydryl (T‐SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ‐induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP‐SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ‐induced oxidative damage by reducing TBARS levels and increasing NP‐SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels. KEYWORDS atorvastatin, diabetes mellitus, lipid peroxidation, liver enzymes, streptozotocin (STZ) 1 | INTRODUCTION The World Health Organization reported that there were 422 million patients with diabetes worldwide in 2014. [1] Diabetes is a metabolic disease that has been linked to hyperglycemia and develops as a result of defects in insulin release, insulin resistance, or both. There are several mechanisms underlying the insulin resistance and metabolic disorders in different subtypes of diabetes. [2] Type 1 diabetes results in damage to different tissues, including the heart, kidneys, retina, and nerves, and leads to serious complications. [3] Combinations of insulin with other therapies, including statins, for the treatment of type 1 diabetes has recently been suggested to be effective in reducing cardiovascular risk. [4] Statins are drugs that reduce cholesterol levels by inhibiting the hydroxymethylglutaryl‐ coenzyme A (HMG‐CoA) reductase enzyme, which plays a crucial role in cholesterol synthesis in the liver. [5–7] These are among the most commonly prescribed medicines worldwide for the prevention of cardiovascular complications and mortality, and studies have suggested that, in addition to decreasing serum lipids, statins also show pleiotropic effects that are not directly associated with cholesterol synthesis, such as improving endothelial dysfunction, reducing inflammatory response, stabilizing atherosclerotic plaque, and decreasing thrombogenic response. [7] Compared with hydro- philic statins (eg, pravastatin), lipophilic statins (egatorvastatin and J Biochem Mol Toxicol. 2019;e22295. wileyonlinelibrary.com/journal/jbt © 2019 Wiley Periodicals, Inc. | 1 of 6 https://doi.org/10.1002/jbt.22295