Antioxidant enzymes activities and plasma levels of oxidative stress markers in B-chronic lymphocytic leukemia patients I. Zelen 1 , P. Djurdjevic 2 , S. Popovic 3 , M. Stojanovic 1 , V. Jakovljevic 4 , S. Radivojevic 5 , D. Baskic 3 , N. Arsenijevic 3 1 Department of Biochemistry, 2 Department of Pathophysiology, 3 Department of Microbiology and Immunology, 4 Department of Physi- ology, Faculty of Medicine, University of Kragujevac; 5 Clinical Center Kragujevac, Kragujevac, Serbia Summary Purpose: Overproduction of reactive oxygen species (ROS) intermediates above the functional capability of cel- lular antioxidants may result in instability of important mac- romolecules and represents the molecular basis of many dis- eases including infammation processes, cardiovascular al- terations, cancer etc. The purpose of this study was to deter- mine plasma level of superoxide anion, hydrogen-peroxide and malondialdehyde (MDA) as markers of oxidative stress and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) as antioxidant enzymes in B-chronic lymphocytic leukemia (B-CLL) patients. Methods: The study included 29 untreated B-CLL pa- tients in stage A, and 21 in stages B and C, classifed accord- ing to the Binet system; 31 healthy volunteers formed the control group. After centrifugation of heparinized peripheral blood, plasma levels of all investigated parameters were de- termined using spectrophotometric methods. Results: Plasma CAT activity was increased in B-CLL patients compared with control subjects; also, progression of disease was related with signifcantly higher plasma activi- ty of CAT. Also, B-CLL patients showed signifcantly higher plasma concentration of MDA compared with controls. No statistically signifcant differences of superoxide anion and hydrogen peroxide as well as plasma activity of SOD and GPx between the tested groups were noted. Conclusion: Increase of CAT activity in B-CLL patients indicates that there is stimulation of the antioxidant enzyme system, while the increase of MDA concentration shows in- creased lipid peroxidation level. According to these results it could be concluded that an imbalance exists between oxi- dants and antioxidants in the plasma of B-CLL patients. Key words: catalase, chronic lymphocytic leukemia, gluta- thione peroxidase, malondialdehyde, reactive oxygen spe- cies, superoxide dismutase Introduction CLL is a predominantly clonal B cell neoplasm of small, resting, long-living B-cells. Despite recent ad- vances in the understanding of the genetics [1], biology [2], clinical behavior [3] and treatment [4], there is no established treatment for CLL and its progression and outcome are highly unpredictable. Expansion of malig- nant cells leads to their accumulation in the peripheral blood, bone marrow and many tissues. These cells are functionally defective and immunologically distinct from normal B cells [5]. The clinical course of B-CLL is highly heterogeneous, ranging from less than 2 years in symptomatic patients with advanced disease to more than 20 years for patients with an early stage and non- progressive disease [6]. Although the pathogenesis of B-CLL is not fully elucidated, the progressive increase of lymphocyte count coupled with the very low pro- portion of proliferating cells has led to the notion that B-CLL may be determined by defective apoptosis [7]. The precise mechanisms underlying apoptosis still re- main largely unknown. Dysregulation of p53, c-myc and bcl-2 oncogenes can be a cause of defective apoptosis in B-CLL [8]. And, even though the B-CLL cells molecular alterations involving different oncogenes and tumor sup- pressor genes have been established, the role of oxida- tive stress in the pathogenesis of this disease is poorly understood and remains a matter of research [9]. Correspondence to: Ivanka Zelen, MD, PhD. Department of Biochemistry, Faculty of Medicine, University of Kragujevac, S. Markovica 69, 34 000 Kragujevac, Serbia. Tel: +381 34 342 941, Fax: +381 34 306 800, 112; E-mail: izelen@medf.kg.ac.yu, ivankazelen@gmail.com Received 22-04-2009; Accepted 03-07-2009 Journal of BUON 15: 330-336, 2010 © 2010 Zerbinis Medical Publications. Printed in Greece ORIGINAL ARTICLE