Original Article Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde, and thiol levels in patients with restless legs syndrome Gülden Baskol a , Selda Korkmaz b , Feray Erdem a , Aysen Caniklioglu a , Merve Kocyigit c , Murat Aksu c,⇑ a Department of Biochemistry, Erciyes University Faculty of Medicine, Kayseri, Turkey b Department of Neurology, Acibadem Hospital, Kayseri, Turkey c Department of Neurology, Erciyes University Faculty of Medicine, Kayseri, Turkey article info Article history: Received 20 April 2011 Received in revised form 25 November 2011 Accepted 26 November 2011 Keywords: Restless legs syndrome Nitric oxide Malondialdehyde Advanced oxidation protein products abstract Objectives: We aimed to determine the importance of oxidative stress in the pathogenesis of restless legs syndrome (RLS) by quantification of advanced oxidation protein products and total thiol levels (as mark- ers of oxidative protein damage), nitric oxide levels (as an antioxidant and endothelial function), and mal- ondialdehyde levels (as a marker of lipid peroxidation) in patients with RLS. Design and methods: A total of 22 patients with primary RLS were enrolled in the study and 20 age-and- gender-matched healthy subjects were enrolled as a control group. Serum nitric oxide, malondialdehyde, thiol levels, and plasma advanced oxidation protein products levels were determined by spectrophoto- metric methods. Results: Serum nitric oxide and thiol levels were lower in the patient group than in controls (p = 0.007 and p = 0.017, respectively). Plasma advanced oxidation protein products levels and serum malondialde- hyde levels were found to be higher in patients with RLS than in controls (p = 0.017 and p = 0.008, respec- tively). Serum malondialdehyde level was found to be positively correlated with plasma advanced oxidation protein products levels (p = 0.039). Serum thiol level was found to be negatively correlated with plasma advanced oxidation protein products levels (p = 0.030). Conclusions: Increased advanced oxidation protein products, malondialdehyde levels, and decreased thiol and nitric oxide levels, may suggest that patients with RLS are under oxidative stress. Although both lipid peroxidation and protein oxidation may have a role in atherosclerosis in RLS, those factors may be related to the pathogenesis of RLS. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Restless legs syndrome (RLS) is a common neurological disorder that is characterized by an urge to move the legs (and, rarely, the arms as well) and peculiar, unpleasant sensations. The diagnosis is based on clinical criteria: an urge to move the legs, usually asso- ciated with unpleasant sensations; symptoms occurring during periods of rest, such as sitting or lying down; symptoms relieved by movement; and symptoms that are worse in the evening or night. The etiology and pathogenesis of RLS are still poorly under- stood [1,2]. Oxidative stress is defined as a process in which the dynamic re- dox balance between oxidants and antioxidants is intensely shifted toward oxidative potentials. Reactive oxygen species are highly reactive molecules that, when present in excess, overwhelm the protective systems and results in cell damage and protein and lipid peroxidation [3]. Since the reactive oxygen species removal rate is mostly controlled by a variety of antioxidants, there is a great interest in determining their levels and the way they are related to pathological states [4]. In 1996 a new oxidative stress biomarker, referred to as ad- vanced oxidation protein products, was detected in the plasma of chronic uremic patients [5]. Advanced oxidation protein products formed in vitro when serum albumin was exposed to hypochlorous acid. In vivo, plasma concentration of advanced oxidation protein products closely correlated with levels of dityrosine, a hallmark of oxidized protein, and pentosidine, a marker of protein glycoxi- dation that is tightly related to oxidative stress. Advanced oxida- tion protein products result from the interaction between such oxidants and plasma proteins. Thus, advanced oxidation protein products might be formed during oxidative stress by reaction of plasma proteins with chlorinated oxidants and have been consid- ered novel markers of oxidant-mediated protein damage [6]. The endothelial cells play a pivotal role in the regulation of vas- cular homeostasis [7]. One of them is the synthesis of nitric oxide, which is responsible for endothelial vasorelaxation and inhibition 1389-9457/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.sleep.2011.11.012 ⇑ Corresponding author. Tel.: +90 533 3638980; fax: +90 352 4378662. E-mail address: aksu@erciyes.edu.tr (M. Aksu). Sleep Medicine 13 (2012) 414–418 Contents lists available at SciVerse ScienceDirect Sleep Medicine journal homepage: www.elsevier.com/locate/sleep