High-cholesterol diet increases xanthine oxidase and decreases nitric oxide synthase activities in erythrocytes from rats Erdinç Devrim a, ⁎ , İmge B. Ergüder a , Hanefi Özbek b , İlker Durak a a Department of Biochemistry, Ankara University Faculty of Medicine, 06100 Ankara, Turkey b Department of Pharmacology, Yüzüncü Yıl University Faculty of Medicine, 65080 Van, Turkey Received 24 April 2007; revised 25 December 2007; accepted 16 January 2008 Abstract The aim of this study was to investigate the effects of a high-cholesterol diet on oxidant/ antioxidant status and nitric oxide synthase (NOS) activity in erythrocytes from rats. Sixteen Sprague-Dawley–type albino male rats were used in the study. The rats were randomly divided into 2 groups: the control group (group 1) was fed a standard rat diet, and the treated group (group 2) was fed a high-cholesterol diet (4% cholesterol, 1% cholic acid, and 0.5% thiouracil) in addition to standard pellet rat diet for 3 months. At the end of the study period, blood samples were obtained from the rats under ether anesthesia. Oxidant (malondialdehyde level, sensitivity to oxidation value, and xanthine oxidase [XO] activity) and antioxidant parameters (antioxidant potential value, superoxide dismutase, catalase, and glutathione peroxidase activities) were studied in erythrocyte preparations. Activities of erythrocyte NOS and arginase enzymes and serum total cholesterol levels were also measured. We observed that serum total cholesterol levels, erythrocyte XO activities, and sensitivity to oxidation values significantly increased in group 2 (cholesterol fed) compared with the control group (group 1). Erythrocyte NOS activities were also found to decrease in group 2. In conclusion, our results suggest that cholesterol feeding causes an increase in XO activity and a decrease in NOS activity in the erythrocytes from rats. The increase in XO activity may render the erythrocyte membranes sensitive to oxidant stress, and the decrease in NOS activity in the erythrocytes may increase cardiovascular disease risk via reduced endothelial relaxation. © 2008 Elsevier Inc. All rights reserved. Keywords: Erythrocytes; Hypercholesterolemia; Oxidant/antioxidant status; Nitric oxide synthase (NOS); Rat Abbreviations: AOP, antioxidant potential; CAT, catalase; GSH-Px, glutathione peroxidase; MDA, malondialdehyde; NO, nitric oxide; NOS, nitric oxide synthase; SOD, superoxide dismutase; SOx, sensitivity to oxidation; TC, total cholesterol; XO, xanthine oxidase. 1. Introduction Atherosclerosis is the leading cause of death in developed countries [1], but it is also increasing in others. Hypercho- lesterolemia (high blood total cholesterol [TC]) has been known as one of the most important risk factors of atherosclerosis [2]. It has been shown that hypercholester- olemia increases oxidative stress and leads to lipid peroxidation [3]. Oxidative stress occurs when there is an imbalance between prooxidant agents relative to antioxi- dants and antioxidant defense mechanisms. This imbalance may be due to increased production of reactive oxygen species and impaired antioxidant defense [4]. Available online at www.sciencedirect.com Nutrition Research 28 (2008) 212 – 215 www.elsevier.com/locate/nutres ⁎ Corresponding author. Ankara Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Dekanlık Binası,Sıhhiye, 06100 Ankara, Turkey. Tel.: +90 312 3103010 ext. 284; fax: +90 312 3106370. E-mail address: erdincdevrim@yahoo.com (E. Devrim). 0271-5317/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.nutres.2008.01.006