Dyslipidemia and oxidative stress in sarcoidosis patients Jasmina Ivanišević a, ⁎, Jelena Kotur-Stevuljević a , Aleksandra Stefanović a , Zorana Jelić-Ivanović a , Slavica Spasić a , Jelica Videnović-Ivanov b , Violeta Vučinić-Mihailović b , Jasmina Ilić c a Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia b Institute for Pulmonary Diseases and Tuberculosis, Clinical Centre of Serbia, Koste Todorovića 26, 11000 Belgrade, Serbia c Health Centre “St. Luka”, Knez Mihajlova 51, 11300 Smederevo, Serbia abstract article info Article history: Received 27 January 2012 Received in revised form 7 March 2012 Accepted 8 March 2012 Available online 16 March 2012 Keywords: Lipoprotein status Oxidative stress status Sarcoidosis Objectives: Sarcoidosis is an inflammatory disease characterised by enhanced production of reactive ox- ygen species and alterations in the circulating lipid profile. Both attributes are thought to play a role in its pathogenesis. However, current knowledge regarding the significance of blood oxidative stress/anti-oxidant defence as well as alterations in lipid status parameters in sarcoidosis is scarce. The aim of our study was to assess these parameters and their inter-relationships, as well as their potential for patient-control discrimi- nation. Design and methods: Oxidative stress status and anti-oxidant defence parameters were determined in serum and erythrocytes and lipid status parameters were assessed in the serum of 213 treated sarcoidosis pa- tients and 90 controls. Results: Malondialdehyde, superoxide anion, total oxidant status, prooxidant–antioxidant balance and triglycerides were significantly higher whereas total anti-oxidant status, superoxide dismutase activity and HDL-cholesterol were significantly lower in sarcoidosis patients compared with controls. Total sulfhydryl group content was higher in patients compared with controls. Serum and erythrocyte malondialdehyde exhibited the strongest ability to predict disease presence. Elevated oxidative stress was characterised by higher clinical accuracy compared with lipid status abnormality. Some oxidative stress and lipid status markers were significantly associated in sarcoidosis. Conclusions: Sarcoidosis is characterised by increased oxidative stress, diminished overall anti-oxidative protection and alterations in the circulating lipid profile. Both oxidative stress and lipid status parameters demonstrated the potential to discriminate sarcoidosis from controls which was particularly evident from the point of view of oxidative stress status parameters. Association between these parameters may indicate an increased risk for atherosclerosis development. © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Introduction Sarcoidosis is a systemic granulomatous inflammatory disease that primarily affects the lungs and the lymphatic system. The disease is characterised by a hyperimmune response [1] in which the im- mune system cells differentiate and proliferate contributing to granu- loma formation ultimately leading to fibrosis [2]. Differentiation and proliferation of the cells, as well as the inflammation, have been asso- ciated with elevated oxidative stress [3] which may initiate cell injury [4]. Previous studies focusing on the oxidative stress status in serum/ plasma of sarcoidosis patients found a lower level of non-enzymatic anti-oxidative defence [5], increased total hydroperoxides [6], in- creased 8-isoprostane [7], and up-regulated MnSOD [8]. To date scarce data exist regarding the redox balance in erythrocytes of sar- coidosis patients. Rothkrantz-Kos and colleagues found decreased erythrocyte NADPH in female pulmonary sarcoidosis patients, a co- factor required to maintain adequate level of reduced glutathione [9]. Clinical Biochemistry 45 (2012) 677–682 Abbreviations: ROS, reactive oxygen species; MnSOD, Mn superoxide dismutase; NADPH, nicotinamide adenine dinucleotide phosphate; HDL-c, HDL-cholesterol; TC, total cholesterol; LDL-c, LDL-cholesterol; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; DLCO, diffuse capacity of the lung for carbon monoxide; EDTA, ethylen-diamino-tetracetic acid; hs-CRP, high-sensitivity C-reactive protein; ACE, an- giotensin-converting enzyme; MDA, malondialdehyde; TBARS, thiobarbituric acid- reactive substances; NBT, nitroblue tetrazolium chloride; O2.-, superoxide anion; SOD, superoxide dismutase; SH, sulfhydryl groups; DTNB, 5.5′-dithiobis (2-nitrobenzoic acid); TOS, total oxidative status; H2O2, hydrogen peroxide; TAS, total anti-oxidant status; ABTS, 2.2′-azinobis-(3-ethylbenzothiazoline)-6-sulfonic acid; PAB, pro-oxidant-anti- oxidant balance; TMB, 3.3′.5.5′-tetramethylbenzidine; ROC, receiver operating characteristic curves; AUC, area under the curve. ⁎ Corresponding author at: Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, P. Box 146, 11221 Belgrade, Serbia. Fax: +381 11 39 72 840. E-mail address: jasminai@pharmacy.bg.ac.rs (J. Ivanišević). 0009-9120/$ – see front matter © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.clinbiochem.2012.03.009 Contents lists available at SciVerse ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem