Skip to main content
SpringerLink
Log in

Decreased basal activity of HDL associated enzyme: Paraoxonase (PON) during uncompensated oxidative stress among type 2 diabetes mellitus patients

  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

The inverse relationship between serum levels of High Density Lipoprotein (HDL) and the development of Cardio Vascular Disease (CVD) risk among diabetic patients was known for several decades. Besides the decreasing quantity of HDL, the qualitative functions of HDL are adversely affected during uncompensated oxidative stress among diabetics and leads to implication of several complications such as dyslipidemia, lipid peroxidation, endothelial dysfunction and atherosclerosis. Therefore we have undertaken this study to determine anti-atherogenic property of HDL by measuring it's one of the associated enzymes; paraoxonase (PON) among type 2 diabetes patients, along with the serum activity of superoxide dismutase (SOD) as an index of antioxidant status and lipid peroxidation end product, i.e malondialdehyde (MDA) as a marker for oxidative stress. This study included a total of 56 untreated type 2 diabetic patients and 29 healthy volunteers as controls. FBS, PPBS, HbA1C and fasting lipid profile were measured in both the study groups. Activity of basal PON, SOD and plasma MDA levels was determined in both the study groups according to standard clinical laboratory procedures. All the diabetic patients were under poor glycemic control. Serum levels of HDL between the two study groups are not significantly differed. But, serum basal PON and SOD activity were significantly decreased, whereas MDA levels were highly elevated (284 ± 59 nM/mL/min, 111 ± 35 μmol/L, 10.38 ± 4.17 IU/mL respectively) when compared with healthy controls (371 ± 46 nM/mL/min, 63 ± 12 μmol/L, 16.91 ± 2.89 IU/mL respectively). Although there is no significant reduction in concentrations of HDL in diabetics when compared with controls, but there was a significant decrease in anti-atherogenic property i.e. activity of paraoxonase enzyme. Moreover the serum activity of paraoxonase was significant and negatively correlated with MDA levels (r = - 0.53, P < 0.001) as well as with FBS (r = - 0.30, P < 0.05). Therefore the qualitative functions of HDL are significantly affected by hyperglycemia induced oxidative stress. Hence, we concluded that the quality of HDL is most important in order to determine oxidative stress related complications in diabetes mellitus than its concentration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig 2
Fig 3
Fig 4
Fig 5
Fig 6
Fig. 7

Similar content being viewed by others

References

  1. Global health risks: mortality and burden of disease attributable to selected major risks. Geneva: World Health Organization, 2009.

  2. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996;19:257–67.

    Article  PubMed  CAS  Google Scholar 

  3. Young I, Woodside J. Antioxidants in health and disease. J Clin Pathol. 2001;54:176–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Baynes JW. Role of oxidative stress in development of complication in diabetes. Diabetes. 1991;40:405–12.

    Article  PubMed  CAS  Google Scholar 

  5. Barter P. High-density lipoproteins and reverse cholesterol transport. Curr Opin Lipidol. 1993;4:210–7.

    Article  CAS  Google Scholar 

  6. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79:8–15.

    Article  PubMed  CAS  Google Scholar 

  7. Van Lenten BJ, Navab M, Shih D, Fogelman AM, Lusis AJ. The role of high-density lipoproteins in oxidation and inflammation. Trends Cardiovasc Med. 2001;11:155–61.

    Article  PubMed  Google Scholar 

  8. Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, et al. Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med. 1999;26:892–904.

    Article  PubMed  CAS  Google Scholar 

  9. Tall AR. Cholesterol efflux pathways and other potential mechanisms involved in the athero-protective effect of high density lipoproteins. J Intern Med. 2008;263:256–73.

    Article  PubMed  CAS  Google Scholar 

  10. Florentin M, Liberopoulos EN, Wierzbicki AS, Mikhailidis DP. Multiple actions of high-density lipoprotein. Curr Opin Cardiol. 2008;23:370–8.

    Article  PubMed  Google Scholar 

  11. Sviridov D, Mukhamedova N, Remaley AT, Chin-Dusting J, Nestel P. Antiatherogenic functionality of high density lipoprotein: how much versus how good. J Atheroscler Thromb. 2008;15:52–62.

    Article  PubMed  Google Scholar 

  12. Navab M, Reddy ST, Van Lenten BJ, Buga GM, Ananthramaith GM, Fogelman AM. HDL and inflammation. In: Fielding CJ, editor. High-density lipoprotein, from basic biology to clinical aspects. Weinheim: Wiley-VCH Verlag GmbH &Co; 2007. p. 341.

    Google Scholar 

  13. Camont L, Chapman MJ, Kontush A. A. Biological activities of HDL subpopulations and their relevance to cardiovascular disease. Trends Mol Med. 2011;17:594–603.

    Article  PubMed  CAS  Google Scholar 

  14. Hedrick CC, Thorpe SR, Fu MX, Harper CM, Yoo J, Kim SM, et al. Glycation impairs high-density lipoprotein function. Diabetologia. 2000;43:312–20.

    Article  PubMed  CAS  Google Scholar 

  15. Salmon S, Maziere C, Auclair M, Theron L, Santus R, Maziere JC. Malondialdehyde modification and copper-induced autooxidation of high-density lipoprotein decrease cholesterol efflux from human cultured fibroblasts. Biochim Biophys Acta. 1992;1125:230–5.

    Article  PubMed  CAS  Google Scholar 

  16. Szapacs ME, Kim HY, Porter NA, Liebler DC. Identification of proteins adducted by lipid peroxidation products in plasma and modifications of apolipoprotein A1 with a novel biotinylated phospholipid probe. J Proteome Res. 2008;7:4237–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Van der Westhuyzen DR, de Beer FC, Webb NR. HDL cholesterol transport during inflammation. Curr Opin Lipidol. 2007;18:147–51.

    Article  PubMed  CAS  Google Scholar 

  18. Alridge WN. A-esterase and B-esterase in perspective. In: Reiner E, Alridge WN, Hoskin FCG, editors. Enzymes hydrolyzing organophosphorous compounds. Chichester: Elis Horwood Ltd; 1989. p. 1–14.

    Google Scholar 

  19. Gonzalvo MC, Gil F, Hernandez AF. Human liver paraoxonase (PON1) sub-cellular distribution and characterization. J Biochem Mol Toxicol. 1998;12:61–9.

    Article  PubMed  CAS  Google Scholar 

  20. Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis. 1995;115:243–53.

    Article  PubMed  CAS  Google Scholar 

  21. Watson AD, Berliner JA, Hamsa SY, et al. Protective effect of high density lipoprotein associated paraoxonase: inhibition of the biological activity of minimally oxidized low density lipoproteins. J Clin Invest. 1995;96:2882–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. McElveen J, Mackness MI, Colley CM, Peard T, Warner S, Walker CH. Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction. Clin Chem. 1986;32:671–3.

    PubMed  CAS  Google Scholar 

  23. Mackness MI, Harty D, Bhatnagar D, Winocour PH, Arrol S, Ishola M, et al. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis. 1991;86:193–9.

    Article  PubMed  CAS  Google Scholar 

  24. Marklund SL. Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci. 1982;79:7634–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Marklund SL, Holme E, Hellner L. Superoxide dismutase in extracellular fluids. Clin Chim Acta. 1982;126:41–51.

    Article  PubMed  CAS  Google Scholar 

  26. Halliwell B, Gutteridge JMC. Free radicals and toxicology, In: Free Radicals in Biology and Medicine, Clarendon Press, Oxford, 1997, pp. 1–27.

  27. Culotta VC. Superoxide dismutase, oxidative stress, and cell metabolism. Curr Top Cell Regul. 2000;36:117–32.

    Article  PubMed  CAS  Google Scholar 

  28. Zander R, Lang W, Wolf HU. Alkaline haematin D-575, a new tool for the determination of haemoglobin as an alternative to the cyanhaemiglobin method. I. Description of the method. Clin Chim Acta. 1984;136:83–93.

    Article  PubMed  CAS  Google Scholar 

  29. Wolf HU, Lang W, Zander R. Alkaline hematin D-575, a new tool for the determination of hemoglobin as a choice to the cyanhaemiglobin method. II. Standardization of the method using pure chlorohaemin. Clin Chim Acta. 1984;136:95–104.

    Article  PubMed  CAS  Google Scholar 

  30. Kilic SS, Aydin S, Kilic N, Erman F, Aydin S, Celik I. Serum arylesterase and paraoxonase activity in patients with chronic hepatitis. World J Gastroenterol. 2005;11:7351–4.

  31. Draper HH, Hadley M. Maondialdehyde determination as Index of Lipid Peroxidation. Methods Enzymol. 1990;186:421–31.

    Article  PubMed  CAS  Google Scholar 

  32. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47:469–74.

    Article  PubMed  CAS  Google Scholar 

  33. ADA (American Diabetes Association). Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005;28((Suppl 1):S37–43.

    Article  Google Scholar 

  34. West IC. Radicals and oxidative stress in diabetes. Diabet Med. 2000;17:171–80.

    Article  PubMed  CAS  Google Scholar 

  35. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.

  36. Fiorentino TV, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 2013;19:5695–703.

    Article  PubMed  CAS  Google Scholar 

  37. Esterbauer H, Schaur RJ, And Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1991;11:81–128.

    Article  PubMed  CAS  Google Scholar 

  38. Siu GM, Draper HH. Metabolism of malonaldehyde in vivo and in vitro. Lipids. 1982;17:349–55.

    Article  PubMed  CAS  Google Scholar 

  39. Nair SP, Shah NC, Taggarsi A, Nayak U. PON1 and its association with oxidative stress in type I and type II diabetes mellitus. Diabetes Metab Syndr. 2011;5:126–9.

    Article  PubMed  Google Scholar 

  40. Adachi T, Marklund SL. Interactions between human extracellular superoxide dismutase C and sulfated polysaccharides. J Biol Chem. 1989;264:8537–41.

    PubMed  CAS  Google Scholar 

  41. Auchere F, Capeillere-Blandin C. Oxidation of Cu, Zn-superoxide dismutase by the myeloperoxidase/hydrogen peroxide/chloride system: functional and structural effects. Free Radic Res. 2002;36:1185–98.

    Article  PubMed  CAS  Google Scholar 

  42. Michiels C, Raes M, Tounssaint O, Remacle J. Importance of Se-glutathione peroxidise, catalase, and Cu/Zn SOD for cell survival against oxidative stress. Free Radic Biol Med. 1994;17:235–48.

    Article  PubMed  CAS  Google Scholar 

  43. Abbott CA, Mackness MI, Kumar S, Boulton AJ, Durrington PN. Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol. 1995;15:1812–8.

    Article  PubMed  CAS  Google Scholar 

  44. Navab M, Hama SY, Van Lanten BJ, Fonarow GC, Cardinez CJ, Castellani LW, et al. Mildly oxidized LDL induces an increased apolipoprotein j/paraoxonase ratio. J Clin Invest. 1997;99:2005–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Durrington PN, Mackness B, Mackness MI. Review - Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol. 2001;21:473–80.

    Article  PubMed  CAS  Google Scholar 

  46. Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN. Serum Paraoxonase after Myocardial Infarction. Arterioscler Thromb Vasc Biol. 1999;19:330–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank PSG IMS&R for providing research opportunity. Authors wish to thank Dr. Usha Anand, former professor of biochemistry, PSGIMS&R, Coimbatore and Dr. N. Prasada Rao, Professor and Head, Department of Biochemistry, KFMS&R, Coimbatore in helping writing of manuscript. And last authors specially wish to thank MedCalc Software bvba for providing free trial version.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Karpagam Faculty of Medical Sciences & Research, Othakalmandapam, Coimbatore, Tamilnadu, India, 641032

    Y. Dhanunjaya

  2. Department of Biochemistry, PSG Institue of Medical Sciences & Research, Peelamedu, Coimbatore, Tamilnadu, India

    D. Vijaya

  3. Institute of Biochemistry, Madras Medical College & RGGGH, Chennai, Tamilnadu, India, 600003

    Pragna B. Dolia

Authors
  1. Y. Dhanunjaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Vijaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pragna B. Dolia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Dhanunjaya.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhanunjaya, Y., Vijaya, D. & Dolia, P.B. Decreased basal activity of HDL associated enzyme: Paraoxonase (PON) during uncompensated oxidative stress among type 2 diabetes mellitus patients. Int J Diabetes Dev Ctries 35 (Suppl 3), 483–490 (2015). https://doi.org/10.1007/s13410-014-0218-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-014-0218-7

Keywords

Search

Navigation