Investigation of Lipid Peroxidation Products and Antioxidant Enzyme Activities in End-Stage Renal Disease Patients

Bojana Kisic, Dijana Miric, Radojica Stolic, Aleksandra Ilic, Julijana Rasic, Mirjana Miric, Ilija Dragojevic

Faculty of Medicine Pristina, Institute of Biochemistry, Settlement Kosovska Mitrovica, Serbia.
Faculty of Medicine Pristina, Institute of Pathophysiology, Settlement Kosovska Mitrovica, Serbia.
Faculty of Medicine Pristina, Institute of Pharmacology, Settlement Kosovska Mitrovica, Serbia.
Faculty of Medicine Pristina, Institute of Preventive Medicine (Medical Statistics and Informatics), Settlement Kosovska Mitrovica, Serbia.
Internal Clinic Faculty of Medicine Pristina, Settlement Kosovska Mitrovica, Serbia.

DOI: 10.4236/aces.2014.41010                

Abstract

Background: Intravenous application of iron preparations which is a routine treatment of anemia in hemodialysis patients with end-stage renal disease can lead to iron overload in the body. Redox-active iron can catalyze the formation of hydroxyl radicals and initiation of lipid peroxidation, increase oxidative stress and speed up the development of complications in these patients. Objective: In this study, we determined the markers of lipid peroxidation, protein oxidation and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione S-transferase) in serum of patients with end-stage renal disease on hemodialysis, who had received repeated treatment of iron supplementation. Patients and Methods: The study included 29 patients undergoing regular hemodialysis treatment. These patients were divided into three groups according to the serum ferritin levels: group I (serum ferritin between 100 and 300 mg/L); group II (serum ferritin between 301 and 600 mg/L), and group III (serum ferritin above 601 mg/L). Results: The serum of patients with the highest concentration of serum ferritin and iron contained significantly higher level of lipid peroxidation products, total hydroperoxides and malondialdehyde and advanced oxidation protein products and the lowest concentration of sulfhydryl groups, reduced glutathione and total antioxidant capacity. Conclusion: Based on the obtained results, it can be concluded that iron supplementation in hemodialysis patients and consequently body iron overload of exacerbated oxidative stress have already been present in these patients.

Keywords

Oxidative Stress; Hemodialysis; Ferritin; Antioxidant Enzymes; Lipid Peroxidation

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	C. Libetta, V. Sepe, P. Esposito, F. Galli and A. Dal Canton, “Oxidative Stress and Inflammation: Implications in Uremia and Hemodialysis,” Clinical Biochemistry, Vol. 44, No. 14-15, 2011, pp. 1189-1198. http://dx.doi.org/10.1016/j.clinbiochem.2011.06.988
[2]	M. Morena, S. Delbosc, A. M. Dupuy, B. Canaud and J. P. Cristol, “Overproduction of Reactive Oxygen Species in End-Stage Renal Disease Patients: A Potential Component of Hemodialysis-Associated Inflammation,” Hemodialysis International, Vol. 9, No. 1, 2005, pp. 37-46. http://dx.doi.org/10.1111/j.1492-7535.2005.01116.x
[3]	Z. M. Dimitrijevic, T. P. Cvetkovic, V. M. Djordjevic, D. D. Pavlovic, N. Z. Stefanovic, I. R. Stojanovic, G. J. Paunovic and R. M. Velickovic-Radovanovic, “How the Duration Period of Erythropoietin Treatment Influences the Oxidative Status of Hemodialysis Patients,” International Journal of Medical Sciences, Vol. 9, No. 9, 2010, pp. 808-815. http://dx.doi.org/10.7150/ijms.4910
[4]	L. Del Vecchio, F. Locatelli and M. Carini, “WHAT WE Know about Oxidative Stress in Patients with Chronic Kidney Disease on Dialysis-Clinical Effects, Potential Treatment, and Prevention,” Seminars in Dialysis, Vol. 24, No. 1, 2011, pp. 56-64. http://dx.doi.org/10.1111/j.1525-139X.2010.00819.x
[5]	D. W. Grabe, “Update on Clinical Practice Recommendations and New Therapeutic Modalities for Treating Anemia in Patients with Chronic Kidney Disease,” American Journal of Health-System Pharmacy, Vol. 64, Suppl. 8, 2007, pp. 8-14. http://dx.doi.org/10.2146/ajhp070182
[6]	M. P. Kooistra, S. Kersting, I. Gosriwatana, S. Lu, J. Nijhoff-Schutte, R. C. Hider and J. J. Marx, “Nontransferrin-Bound Iron in the Plasma of Haemodialysis Patients after Intravenous Iron Saccharate Infusion,” European Journal of Clinical Investigation, Vol. 32, Suppl. 1, 2002, pp. 36-41. http://dx.doi.org/10.1046/j.1365-2362.2002.0320s1036.x
[7]	K. Jomova and M. Valko, “Advances in Metal-Induced Oxidative Stress and Human Disease,” Toxicology, Vol. 283, No. 2-3, 2011, pp. 65-87. http://dx.doi.org/10.1016/j.tox.2011.03.001
[8]	M. A. Sochaski, W. J. Bartfay, S. R. Thorpe, J. W. Baynes, E. Bartfay, D. C. Lehotay and P. P. Liu, “Lipid Peroxidation and Protein Modification in a Mouse Model of Chronic Iron Overload,” Metabolism, Vol. 51, No. 5, pp. 645-651. http://dx.doi.org/10.1053/meta.2002.30530
[9]	J. Mimic-Oka, A. Savic-Radojevic, M. Pljesa-Ercegovac, M. Opacic, T. Simic, N. Dimkovic and D. V. Simic, “Evaluation of Oxidative Stress after Repeated Intravenous Iron Supplementation,” Renal Failure, Vol. 27, No. 3, 2005, pp. 345-351.
[10]	J. Nourooz-Zadeh, J. Tajaddini-Sarmadi and S. P. Wolff, “Measurement of Plasma Hydroperoxide Concentrations by the Ferrous Oxidation-Xylenol Orange Assay in Conjunction with Triphenylphosphine,” Analytical Biochemistry, Vol. 220, No. 2, 1994, pp. 403-409. http://dx.doi.org/10.1053/meta.2002.30530
[11]	A. M. Jentzsch, H. Bachmann, P. Furst and H. K. Biesalski, “Improved Analysis of Malondialdehyde in Human Body Fluids,” Free Radical Biology and Medicine, Vol. 20, No. 2, 1996, pp. 251-256. http://dx.doi.org/10.1016/0891-5849(95)02043-8
[12]	B. Anderstam, B. Ann-Christin, A. Valli, P. Stenvinkel, B. Lindholm and M. E. Suliman, “Modification of the Oxidative Stress Biomarker AOPP Assay: Application in Uremic Samples,” Clinica Chimica Acta, Vol. 393, No. 2, 2008, pp. 114-118. http://dx.doi.org/10.1016/j.cca.2008.03.029
[13]	E. Beutler, O. Duron and B. M. Kelly, “Improved Method for the Determination of Blood Glutathione,” Journal of Laboratory and Clinical Medicine, Vol. 61, No. 3, 1963, pp. 882-888.
[14]	H. P. Misra and I. Fridovich, “The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase,” The Journal of Biological Chemistry, Vol. 247, No. 10, 1972, pp. 3170-3175.
[15]	J. T. Rotruck, A. L. Pope, H. E. Ganther, A. B. Swanson, D. G. Hafeman and W. G. Hoekstra, “Selenium: Biochemical Roles as a Component of Glutathione Peroxidase,” Science, Vol. 179, No. 4073, 1973, pp. 588-590. http://www.jstor.org/stable/1735448 http://dx.doi.org/10.1126/science.179.4073.588
[16]	M. Habdous, M. Vincent-Viry, S. Visvikis and G. Siest, “Rapid Spectrophotometric Method for Serum Glutathione S-Transferase Activity,” Clinica Chimica Acta, Vol. 326, No. 1-2, 2002, pp. 131-142. http://dx.doi.org/10.1016/S0009-8981(02)00329-7
[17]	E. Racker, “Glutathione Reductase from Baker’s Yeast and Beef Liver,” The Journal of Biological Chemistry, Vol. 217, No. 2, 1955, pp. 855-865. http://www.jbc.org/content/217/2/855
[18]	O. Erel, “A Novel Automated Method to Measure Total Antioxidant Response against Potent Free Radical Reactions,” Clinical Biochemistry, Vol. 37, No. 2, 2004, pp. 112-119. http://dx.doi.org/10.1016/j.clinbiochem.2003.10.014
[19]	P. S. Lim, Y. H. Wei, Y. L. Yu and B. Kho, “Enhanced Oxidative Stress in Haemodialysis Patients Receiving Intravenous Iron Therapy,” Nephrology Dialysis Transplantation, Vol. 14, No. 11, 1999, pp. 2680-2687. http://dx.doi.org/10.1093/ndt/14.11.2680
[20]	M. Valko, H. Morris and M. T. Cronin, “Metals, Toxicity and Oxidative Stress,” Current Medicinal Chemistry, Vol. 12, No. 10, 2005, pp. 1161-1208. http://dx.doi.org/10.2174/0929867053764635
[21]	K. D. Welch, T. Z. Davis, M. E. Van Eden and S. D. Aust, “Deleterious Iron-Mediated Oxidation of Biomolecules,” Free Radical Biology and Medicine, Vol. 32, No. 7, 2002, pp. 577-583. http://dx.doi.org/10.1016/S0891-5849(02)00760-8
[22]	M. Kruszewski, “Labile Iron Pool: The Main Determinant of Cellular Response to Oxidative Stress,” Mutation Research, Vol. 531, No. 1-2, 2003, pp. 81-92. http://dx.doi.org/10.1016/j.mrfmmm.2003.08.004
[23]	L. Tang, Y. Zhang, Z. Qian and X. Shen, “The Mechanism of Fe(2+)-Initiated Lipid Peroxidation in Liposomes: the Dual Function of Ferrous Ions, the Roles of the Pre-Existing Lipid Peroxides and the Lipid Peroxyl Radical,” Biochemical Journal, Vol. 352, Pt 1, 2000, pp. 27-36. http://dx.doi.org/10.1042/0264-6021:3520027
[24]	T. Drüeke, V. Witko-Sarsat, Z. Massy, B. DescampsLatscha, A. P. Guerin, S. J. Marchais, V. Gausson and G. M. London, “Iron Therapy, Advanced Oxidation Protein Products, and Carotid Artery Intima-Media Thickness in End-Stage Renal Disease,” Circulation, Vol. 106, No. 17, 2002, pp. 2212-2217. http://dx.doi.org/10.1161/01.CIR.0000035250.66458.67
[25]	A. K. Salahudeen, B. Oliver, J. D. Bower and L. J. Roberts 2nd, “Increase in Plasma Esterified F2-Isoprostanes Following Intravenous Iron Infusion in Patients on Hemodialysis,” Kidney International, Vol. 60, No. 4, 2001, pp. 1525-1531. http://dx.doi.org/10.1046/j.1523-1755.2001.00976.x
[26]	M. Roehrs, J. Valentini, C. Paniz, A. Moro, M. Charao, R. Bulcao, F. Freitas, et al., “The Relationships between Exogenous and Endogenous Antioxidants with the Lipid Profile and Oxidative Damage in Hemodialysis Patients,” BMC Nephrology, Vol. 12, 2011, pp. 59-68. http://dx.doi.org/10.1186/1471-2369-12-59
[27]	F. Cofan, E. Vela, M. Clèries and Collaborative Study Group for Dyslipidemia, “Analysis of Dyslipidemia in Patients on Chronic Hemodialysis in Catalonia,” Atherosclerosis, Vol. 184, No. 1, 2006, pp. 94-102. http://dx.doi.org/10.1016/j.atherosclerosis.2005.03.021
[28]	K. Pawlak, M. Mysliwiec and D. Pawlak, “Oxidized LDL to Autoantibodies against oxLDL Ratio—The New Biomarker Associated with Carotid Atherosclerosis and Cardiovascular Complications in Dialyzed Patients,” Atherosclerosis, Vol. 224, No. 1, 2012, pp. 252-257. http://dx.doi.org/10.1016/j.atherosclerosis.2012.07.011
[29]	M. Tsumura, T. Kinouchi, S. Ono, T. Nakajima and T. Komoda, “Serum Lipid Metabolism Abnormalities and Change in Lipoprotein Contents in Patients with Advanced-Stage Renal Disease,” Clinica Chimica Acta, Vol. 314, No. 1-2, 2001, pp. 27-37. http://dx.doi.org/10.1016/S0009-8981(01)00681-7
[30]	K. Taki, F. Takayama, Y. Tsuruta and T. Niwa, “Oxidative Stress, Advanced Glycation End Product, and Coronary Artery Calcification in Hemodialysis Patients,” Kidney International, Vol. 70, No. 1, 2006, pp. 218-224. http://dx.doi.org/10.1038/sj.ki.5000330
[31]	V. Witko-Sarsat, M. Friedlander, T. Nguyen Khoa, C. Capeillère-Blandin, A. T. Nguyen, S. Canteloup, J. M. Dayer, P. Jungers, T. Drüeke and B. Descamps-Latscha, “Advanced Oxidation Protein Products as Novel Mediators of Inflammation and Monocyte Activation in Chronic Renal Failure,” Journal of Immunology, Vol. 161, No. 5, 1998, pp. 2524-2532. http://www.jimmunol.org/content/161/5/2524
[32]	M. Anraku, K. Kitamura, R. Shintomo, K. Takeuchi, H. Ikeda, J. Nagano, T. Ko, K. Mera, K. Tomita and M. Otagiri, “Effect of Intravenous Iron Administration Frequency on AOPP and Inflammatory Biomarkers in Chronic Hemodialysis Patients: A Pilot Study,” Clinical Biochemistry, Vol. 41, No. 14-15, 2008, pp. 1168-1174. http://dx.doi.org/10.1016/j.clinbiochem.2008.07.007