ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 48 of 60
УЖМБС 2019, 4(6): 321–328

Activity 0f Lipoprotein-Associated Paraoxonase-1 Enzymes and Myeloperoxidase in Patients with Chronic Kidney Disease

Vasilchenko V. 1,2, Dunaevskaya O.3, Korol L. 1, Kuchmenko O. 2, Stepanova N. 1

Developing of comorbidities associated with impaired immune and cardiovascular function in patients with chronic kidney disease is impossible. That is why the study of potential indicators of the development of pathological conditions of the cardiovascular system in patients with chronic kidney disease is relevant and necessary. The purpose of the work was to study the qualitative state of lipoproteins, enzyme activity, in patients with chronic kidney disease. Material and methods. To achieve this goal, the activity of paraoxonase-1 and serum myeloperoxidase was determined in 36 patients with chronic kidney disease. The activity of paraoxonase-1 was determined spectrophotometrically by the number of phenolic complexes formed using phenylacetate; myeloperoxidase activity was researched by reaction with hydrogen peroxide in the presence and without its specific inhibitor (gamma-aminobenzoic acid). Results and discussion. According to the results of our studies, the activity of paraoxonase-1 in the reference group of conditionally healthy individuals was 6.57 kU / l. In the group of patients with stage I-II of chronic kidney disease enzyme activity decreased by 30% (4,58 kU / l) and in the group of patients with stage V of chronic kidney disease it decreased by 46% (3,55 kU / l) compared with the reference group. Data analysis by the Kruskal-Wallis test (P <0.05) confirmed the difference between the groups. Dunn’s test indicated that there was a difference between control and both groups of patients (P <0.05). Myeloperoxidase activity in patients in group 1 was almost halved to an average of 0.12 conventional units / l, and in patients in group 2, on the contrary, increased 1.5 times (up to 0.37 conventional units / l). Data analysis using the Kruskal-Wallis (P <0.05) and Dunn’s tests established the difference between control and patient groups (P <0.05). Conclusion. The decreased paraoxonase-1 activity was observed in both groups of patients with chronic kidney disease compared with controls. Increased myeloperoxidase activity was observed in patients with stage V of chronic kidney disease, and a decrease in patients with stage I of chronic kidney disease. Thus, the activity of enzymes, in the composition of high-density lipoproteins, reflected their functional status and indicated pathological changes in the body, more pronounced in patients with stage V of chronic kidney disease. We suggest using the activity of paraoxonase-1 and myeloperoxidase as potential markers to prevent the development of complications of cardiovascular disease in patients with chronic kidney disease.

Keywords: paraoxonase-1, myeloperoxidase, chronic kidney disease, cardiovascular disease, oxidative status

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  1. Goldstein JL, Brown MS. A Century of Cholesterol and Coronaries: From Plaques to Genesto Statins. Cell. 2017; 161(1): 161-72.
  2. Lieberman AP, Swanson JA. High Cholesterol at the Heart of Phagolysosomal Damage. Cell Metab. 2018; 27(3): 487-8.
  3. Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015; 15: 104–16.
  4. Mahmood SS, Levy D, Vasan RS, Wang TJ. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet. 2014; 383(9921): 999-1008.
  5. Song J, Ping L, Duong D, Gao X, He C, Wei L, et al. Native low density lipoprotein promotes lipid raft formation in macrophages. Mol Med Rep. 2016 Mar; 13(3): 2087-93.
  6. Kontush A. HDL-mediated mechanisms of protection in cardiovascular disease. Cardiovasc Res. 2014; 103: 341-9.
  7. Rader D, Hovingh K. HDL and cardiovascular disease. Lancet. 2014; 384(9943): 618–25.
  8. Madsen CM, Varbo A, Nordestgaard BG. Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies. Eur Heart J. 2017; 38(32): 2478-86.
  9. Spracklen CN, Chen P, Kim YJ, Wang X, Cai H, Li S, et al. Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels. Hum Mol Genet. 2017; 26(9): 1770–84.
  10. Rasmiena АA, Barlowa CK, Ng TW, Meikle PJ. High density lipoprotein efficiently accepts surface but not internal oxidised lipids from oxidised low density lipoprotein. Biochim Biophys Acta. 2016; 1861(2): 69-77.
  11. Kratzer A, Giral H, Landmesser U. High-density lipoproteins as modulators of endothelial cell functions: alterations in patients with coronary artery disease. Cardiovasc Res. 2014; 103: 350-61.
  12. Kovalenko VM, Kuchmenko OB, Mkhitaryan LS. Molekulyarno-henetychni osoblyvosti funktsionuvannya paraoksonaziv ta yiyi vlastyvosti u rozvytku sertsevo-sudynnoyi patolohiyi. Ukrayin Kardiol zhurn. 2014; 5: 105-16. [Ukrainian]
  13. Rader D. Spotlight on HDL biology: new insights in metabolism, function, and translation. Cardiovasc Res. 2014; 103: 337-40.
  14. Gordon SM, Remaley AT. High density lipoproteins are modulators of protease activity: Implications in inflammation, complement activation, and atherothrombosis. Atherosclerosis. 2017 Nov 16; 259: 104-13.
  15. Ungurianu A, Margina D, Gradinaru D, Bacanu C, Ilie M, Tsitismpikoungurianu C, et al. Lipoprotein redox status evaluation as a marker of cardiovascular disease risk in patients with inflammatory disease. Mol Med Rep. 2017 Nov 14; 15: 256-62.
  16. Koeth RA, Haselden V, Tang WH. Myeloperoxidase in cardiovascular disease. Adv Clin Chem. 2013; 62: 11–32.
  17. Teng N, Maghzal GJ, Talib J, Rashid I, Lau AK, Stocker R. The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture. Redox Report. 2016 Nov25; 22(2): 51-73.
  18. Baseri M, Heidari R, Mahaki B, Hajizadeh Y, Momenizadeh A, Sadeghi M. Myeloperoxidase levels predicts angiographic severity of coronary artery disease in patients with chronic stable angina. Adv Biomed Res. 2014 March 12; 3: 137.
  19. Van der Stoep M, Korporaal SJ, Van Eck M.. High-density lipoprotein as a modulator of platelet and coagulation responses. Cardiovasc Res. 2014 June 1: 103(3): 362-71.
  20. Chistiakov DA, Melnichenko AA, Orekhov AN, Bobryshev YV. Paraoxonase and atherosclerosis-related cardiovascular diseases. Biochimie. 2017 Oct 19; 132: 19-27.
  21. Ku E, Mitsnefes MM. Cardiovascular disease in young adults with incident ESRD. Nat Rev Nephrol. 2019 Jul; 15(7): 390-1.
  22. Zhou C, Cao J, Shang L, Tong C, Hu H, Wang H, et al. Reduced Paraoxonase 1 Activityas a Marker for Severe Coronary Artery Disease. Dis Markers. 2013 Jul 28; 35(2): 97–103.
  23. Gaal K, Lorincz H, Seres I, Harangi M, Olah AV, Paragh G. Characterization of a novel high-density lipoprotein antioxidant capacity assay and its application to high-density lipoprotein fractions. Clin Biochemistry. 2013 Jan 24; 46: 825–7.
  24. Gorudko IV, Cherkalina OS, Sokolov AV, Pulina MO, Zaharova ET, Vasilev VB, i dr. Novyie podhodyi k opredeleniyu kontsentratsii i peroksidaznoy aktivnosti mieloperoksidazyi v plazme krovi cheloveka. Bioorganicheskaya himiya. 2009; 35(5): 629–39. [Russian]
  25. Miljkovic M, Stefanovic A, Vekic J, Zeljkovic A, Gojkovic T, Simic-Ogrizovic S, et al. Activity of paraoxonase 1 (PON1) on HDL2 and HDL3 subclasses in renal disease. Clin Biochem. 2018 Sep; 60: 52-8.
  26. Mohammed CJ, Xie Y, Brewster PS, Ghosh S, Dube P, Sarsouret T, et al. Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease. J Clin Med. 2019; 8(7): 1034.
  27. Ristovski-Kornic D, Stefanović A, Kotur-Stevuljević J, Zeljković A, Spasojević-Kalimanovska V, Vekić J, et al. Association of Myeloperoxidase and the Atherogenic Index of Plasma in Children with End-Stage Renal Disease. J Med Biochem. 2017 Jan 25; 36(1): 23–31. .
  28. Vaziri ND. HDL abnormalities in nephrotic syndrome and chronic kidney disease. Nat Rev Nephrol. 2016 Jan; 12(1): 37-47.
  29. Hammadah МН, Kalogeropoulos АР, Georgiopoulou VV, Weber М, Wu Y, Haze SL, et al. High-density lipoprotein-associated paraoxonase-1 activity for prediction of adverse outcomes in outpatients with chronic heart failure. Eur J Heart Fail. 2017 Jun; 19(6): 748-55.
  30. Duni A, Liakopoulos V, Rapsomanikis KP, Dounousi E. Chronic Kidney Disease and Disproportionally Increased Cardiovascular Damage: Does Oxidative Stress Explain the Burden? Oxid Med Cell Longev. 2017; 2017: 9036450.
  31. Efe TH, Ertem AG, Altunoglu A, Koseoglu C, Erayman A, Bilgin M, et al. Paraoxonase Levels are Correlated with Impaired Aortic Functions in Patients with Chronic Kidney Disease. Acta Cardiol Sin. 2016 Jan; 32(1): 75–80.
  32. Samouilidou E, Kostopoulos V, Liaouri A, Kioussi E, Vassiliou K, Bountou E, et al. Association of lipid profile with serum PON1 concentration in patients with chronic kidney disease. Ren Fail. 2016 Nov; 38(10): 1601-6.
  33. Franck T, Minguet G, Delporte C, Derochette S, Boudjeltia KZ, Antwerpen PV, et al. An immunological method to combine the measurement of active and total myeloperoxidase on the same biological fluid, and its application in finding inhibitors which interact directly with the enzyme. Free Radic Res. 2015 May 27; 49(6): 790–9.
  34. Kisic B, Miric D, Dragojevic I, Rasic J, Popovic L. Role of Myeloperoxidase in Patients with Chronic Kidney Disease. Oxid Med Cell Longev. 2016; 1069743.
  35. Afshinnia F, Zeng L, Byun J, Gadegbeku CA, Magnone MC, Whatling C, et al. Myeloperoxidase Levels and Its Product 3-Chlorotyrosine Predict Chronic Kidney Disease Severity and Associated Coronary Artery Disease. Ам J Nephrol. 2017; 46(1): 73-81.
  36. Zeng L, Mathew AV, Byun J, Atkins KB, Brosius FC, Pennathur S. Myeloperoxidase-derived oxidants damage artery wall proteins in an animal model of chronic kidney disease-accelerated atherosclerosis. J Biol Chem. 2018 May 11; 293(19): 7238-49.