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Decreased paraoxonase activity in critically ill patients with sepsis

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Abstract

Paraoxonase 1 is believed to play a role in preventing lipid oxidation and, thus, limiting production of proinflammatory mediators. Systemic inflammatory response in sepsis increases oxidative stress and decreases high-density lipoprotein (HDL) concentrations. The objective of this study was to investigate serum paraoxonase 1 activities in critically ill patients with sepsis and after recovery. Serum paraoxonase 1 arylesterase/paraoxonase activities, concentration of total cholesterol, HDL cholesterol (HDL-C) and serum C-reactive protein (CRP) in septic patients of a medical intensive care unit (n = 30) and age/sex-matched outpatient controls without sepsis (n = 30) were analyzed. Paired convalescent samples were also taken 1 week after recovery (n = 11). In septic patients, both arylesterase (88.3 ± 36.5 vs. 162.1 ± 44.8 kU/l, P < 0.001) and paraoxonase (75.2 ± 50.0 vs. 125.2 ± 69.4 U/l, P < 0.01) paraoxonase 1 activities decreased as compared to controls. Both activities normalized after recovery. Negative correlation was found between CRP and both arylesterase (r = −0.676, P < 0.001) and paraoxonase (r = −0.401, P < 0.01) as well as positive correlation between HDL-C and both arylesterase (r = 0.585, P < 0.001) and paraoxonase (r = 0.405, P < 0.01) paraoxonase 1 activities. The decreased activity of paraoxonase 1 in negative correlation with CRP offers a potentially useful marker of sepsis progress and recovery in critically ill patients.

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References

  1. Balk RA (2000) Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin 16:179–192

    Article  CAS  PubMed  Google Scholar 

  2. Martins PS, Kallas EG, Neto MC, Dalboni MA, Blecher S, Salomao R (2003) Upregulation of reactive oxygen species generation and phagocytosis, and increased apoptosis in human neutrophils during severe sepsis and septic shock. Shock 20:208–212

    Article  CAS  PubMed  Google Scholar 

  3. Alvarez C, Ramos A (1986) Lipids, lipoproteins, and apoproteins in serum during infection. Clin Chem 32:142–145

    CAS  PubMed  Google Scholar 

  4. van Leeuwen HJ, Heezius EC, Dallinga GM, van Strijp JA, Verhoef J, van Kessel KP (2003) Lipoprotein metabolism in patients with severe sepsis. Crit Care Med 31:1359–1366

    Article  PubMed  Google Scholar 

  5. James RW, Deakin SP (2004) The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity. Free Radic Biol Med 37:1986–1994

    Article  CAS  PubMed  Google Scholar 

  6. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M (1995) Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96:2882–2891

    Article  CAS  PubMed  Google Scholar 

  7. Wu A, Hinds CJ, Thiemermann C (2004) High-density lipoproteins in sepsis and septic shock: metabolism, actions, and therapeutic applications. Shock 21:210–221

    Article  PubMed  Google Scholar 

  8. McElveen J, Mackness MI, Colley CM, Peard T, Warner S, Walker CH (1986) Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction. Clin Chem 32:671–673

    CAS  PubMed  Google Scholar 

  9. Chait A, Han CY, Oram JF, Heinecke JW (2005) Thematic review series: the immune system and atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J Lipid Res 46:389–403

    Article  CAS  PubMed  Google Scholar 

  10. Mackness B, Hine D, McElduff P, Mackness M (2006) High C-reactive protein and low paraoxonase1 in diabetes as risk factors for coronary heart disease. Atherosclerosis 186:396–401

    Article  CAS  PubMed  Google Scholar 

  11. Dirican M, Akca R, Sarandol E, Dilek K (2004) Serum paraoxonase activity in uremic predialysis and hemodialysis patients. J Nephrol 17:813–818

    CAS  PubMed  Google Scholar 

  12. Boehm D, Krzystek-Korpacka M, Neubauer K, Matusiewicz M, Berdowska I, Zielinski B, Paradowski L, Gamian A (2009) Paraoxonase-1 status in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 15:93–99

    Article  PubMed  Google Scholar 

  13. Kumon Y, Nakauchi Y, Kidawara K, Fukushima M, Kobayashi S, Ikeda Y, Suehiro T, Hashimoto K, Sipe JD (1998) A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response. Scand J Immunol 48:419–424

    Article  CAS  PubMed  Google Scholar 

  14. Parra S, Alonso-Villaverde C, Coll B, Ferre N, Marsillach J, Aragones G, Mackness M, Mackness B, Masana L, Joven J, Camps J (2007) Serum paraoxonase-1 activity and concentration are influenced by human immunodeficiency virus infection. Atherosclerosis 194:175–181

    Article  CAS  PubMed  Google Scholar 

  15. Aslan M, Nazligul Y, Horoz M, Bolukbas C, Bolukbas FF, Gur M, Celik H, Erel O (2008) Serum paraoxonase-1 activity in Helicobacter pylori infected subjects. Atherosclerosis 196:270–274

    Article  CAS  PubMed  Google Scholar 

  16. Feingold KR, Memon RA, Moser AH, Grunfeld C (1998) Paraoxonase activity in the serum and hepatic mRNA levels decrease during the acute phase response. Atherosclerosis 139:307–315

    Article  CAS  PubMed  Google Scholar 

  17. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655

    Article  CAS  PubMed  Google Scholar 

  18. Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829

    Article  CAS  PubMed  Google Scholar 

  19. Eckerson HW, Wyte CM, La Du BN (1983) The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 35:1126–1138

    CAS  PubMed  Google Scholar 

  20. Van Lenten BJ, Hama SY, de Beer FC, Stafforini DM, McIntyre TM, Prescott SM, La Du BN, Fogelman AM, Navab M (1995) Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 96:2758–2767

    Article  PubMed  Google Scholar 

  21. Gaidukov L, Tawfik DS (2005) High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I. Biochemistry 44:11843–11854

    Article  CAS  PubMed  Google Scholar 

  22. Ganter U, Arcone R, Toniatti C, Morrone G, Ciliberto G (1989) Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. EMBO J 8:3773–3779

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a research grant from the Czech Ministry of Health (Project No. IGANR/8943-4).

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The authors declare that they have no conflict of interest related to the publication of this manuscript.

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Correspondence to Frantisek Novak.

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Novak, F., Vavrova, L., Kodydkova, J. et al. Decreased paraoxonase activity in critically ill patients with sepsis. Clin Exp Med 10, 21–25 (2010). https://doi.org/10.1007/s10238-009-0059-8

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  • DOI: https://doi.org/10.1007/s10238-009-0059-8

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