Advertisement

Archives of Gynecology and Obstetrics

, Volume 290, Issue 5, pp 929–935 | Cite as

The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome

  • Ayse Carlioglu
  • Ikbal KaygusuzEmail author
  • Feridun Karakurt
  • Ilknur Inegol Gumus
  • Aysel Uysal
  • Benan Kasapoglu
  • Ferah Armutcu
  • Sema Uysal
  • Esra Aktepe Keskin
  • Cemile Koca
General Gynecology

Abstract

Purpose

To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients.

Methods

Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann–Whitney U tests were used for statistical analysis.

Results

PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group.

Conclusion

In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.

Keywords

Polycystic ovary syndrome Platelet activating factor acetyl hydrolyze Oxidized LDL Paraoxonase1 Paraoxonase1 phenotypes Arylesterase 

Notes

Acknowledgments

This study was supported by Fatih University Foundation.

Conflict of interest

No conflict of interest is present for each author.

References

  1. 1.
    Seow KM, Juan CC, Wang PH, Ho LT, Hwang JL (2012) Expression levels of vascular cell adhesion molecule-1 in young and nonobese women with polycystic ovary syndrome. Gynecol Obstet Investig 73(3):236–241CrossRefGoogle Scholar
  2. 2.
    Homburg R (2008) Polycystic ovary syndrome. Clin Obstet Gynaecol 2:261–274Google Scholar
  3. 3.
    Cussons AJ, Stuckey BG, Watts GF (2006) Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives. Atherosclerosis 185:227–239PubMedCrossRefGoogle Scholar
  4. 4.
    Zimmerman GA, McIntyre TM, Prescott SM, Stafforini DM (2002) The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med 30(5):294–301CrossRefGoogle Scholar
  5. 5.
    Stafforini DM (2009) Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2). Cardiovasc Drugs Ther 23(1):73–83PubMedCrossRefGoogle Scholar
  6. 6.
    Caslake MJ, Packard CJ, Suckling KE, Holmes SD, Chamberlain P, Macphee CH (2000) Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis 150:413–419PubMedCrossRefGoogle Scholar
  7. 7.
    Arai H (2014) Oxidative modification of lipoproteins. Subcell Biochem 77:103–114PubMedCrossRefGoogle Scholar
  8. 8.
    Canales A, Sanchez-Munis FJ (2003) Paraoksonaz something more than an enzyme? Med Clin (Barc) 121:537–548CrossRefGoogle Scholar
  9. 9.
    Litvinov D, Mahini H, Garelnabi M (2012) Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. N Am J Med Sci 4(11):523–532PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Aarsman AJ, Neys FW, Van den Bosch H (1991) Catabolism of platelet-activating factor and its acyl analog. Differentiation of the activities of lysophospholipase and platelet-activating-factor acetylhydrolase. Eur J Biochem 200:187–193PubMedCrossRefGoogle Scholar
  11. 11.
    Koubaa N, Nakbi A, Smaoui M et al (2007) Hyperhomocysteinemia and elevated ox-LDL in Tunisian type 2 diabetic patients: role of genetic and dietary factors. Clin Biochem 40(13–14):1007–1014PubMedCrossRefGoogle Scholar
  12. 12.
    Juretic D, Tadijanovic M, Rekic B, Simeon-Rudolf V, Reiner E, Baricic M (2001) Serum paraoxonase activities in hemodialyzed uremic patients: cohort study. Croat Med J 42:146–150PubMedGoogle Scholar
  13. 13.
    Nakanishi M, Takanami Y, Maruyama T, Murata M, Motohashi Y, Nakano S, Uchida K, Maruyama C, Kyotani S, Tsushima M (2003) The ratio of serum paraoxonase/arylesterase activity using an improved assay for arylesterase activity to discriminate PON1(R192) from PON1(Q192). J Atheroscler Thromb 10(6):337–342PubMedCrossRefGoogle Scholar
  14. 14.
    Taketo MM, Sonoshita M (2002) Phospholipase A2 and apoptosis. Biochim Biophys Acta 1585:72–76PubMedCrossRefGoogle Scholar
  15. 15.
    Singh U, Zhong S, Xiong M, Li TB, Sniderman A, Teng BB (2004) Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice. Clin Sci (Lond) 106:421–432CrossRefGoogle Scholar
  16. 16.
    Cederholm A, Svenungsson E, Stengel D et al (2004) Platelet-activating factor acetylhydrolase and other novel risk and protective factors for cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum 50:2869–2876PubMedCrossRefGoogle Scholar
  17. 17.
    Papavasiliou EC, Gouva C, Siamopoulos KC, Tselepis AD (2006) PAF-acetylhydrolase activity in plasma of patients with chronic kidney disease. Effect of long-term therapy with erythropoietin. Nephrol Dial Transpl 21:1270–1277CrossRefGoogle Scholar
  18. 18.
    Milionis HJ, Tambaki AP, Kanioglou CN, Elisaf MS, Tselepis AD, Tsatsoulis A (2005) Thyroid substitution therapy induces high-density lipoprotein-associated platelet activating factor-acetylhydrolase in patients with subclinical hypothyroidism: a potential antiatherogenic effect. Thyroid 15:455–460PubMedCrossRefGoogle Scholar
  19. 19.
    Wan DH, Fan P, Bai H, Song Q, Liu HW (2010) Activity and distribution of plasma platelet-activating factor acetylhydrolase in polycystic ovary syndrome patients with insulin resistance. Zhonghua Fu Chan Ke Za Zhi 45(1):30–34PubMedGoogle Scholar
  20. 20.
    Bayrak T, Dursun P, Bayrak A, Gültekin M, Kolusarı A, Cakır E, Ozyurt M, Zeyneloğlu HB (2012) Paraoxonase lactonase activity (PON-HTLase), asymmetric dimethylarginine (ADMA) and platelet activating factor-acetylhydrolase (PAF-AH) activity in non-obese women with PCOS. Gynecol Endocrinol 28(11):874–878PubMedCrossRefGoogle Scholar
  21. 21.
    Tosi F, Dorizzi R, Castello R et al (2009) Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome. Eur J Endocrinol 161(5):737–745PubMedCrossRefGoogle Scholar
  22. 22.
    Diamanti-Kandarakis E, Paterakis T, Alexandraki K, Piperi C, Aessopos A, Katsikis I, Katsilambros N, Kreatsas G, Panidis D (2006) Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 21:1426–1431PubMedCrossRefGoogle Scholar
  23. 23.
    Jacobson TA (2013) Lipoprotein(a), cardiovascular disease, and contemporary management. Mayo Clin Proc 88(11):1294–1311PubMedCrossRefGoogle Scholar
  24. 24.
    Hackenhaar FS, Martinez D, Medeiros TM et al (2012) Oxidized-LDL and paraoxonase-1 as biomarkers of coronary artery disease in patients with sleep-disordered breathing. Curr Med Chem 19(25):4359–4366PubMedCrossRefGoogle Scholar
  25. 25.
    Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF (2013) Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 19(3):268–288PubMedCrossRefGoogle Scholar
  26. 26.
    Dursun P, Demirtaş E, Bayrak A, Yarali H (2006) Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS? Hum Reprod 21(1):104–108PubMedCrossRefGoogle Scholar
  27. 27.
    Bayram F, Kocer D, Ozsan M, Muhtaroglu S (2012) Evaluation of endothelial dysfunction, lipid metabolism in women with polycystic ovary syndrome: relationship of paraoxonase 1 activity, malondialdehyde levels, low-density lipoprotein subfractions, and endothelial dysfunction. Gynecol Endocrinol 28(7):497–501PubMedCrossRefGoogle Scholar
  28. 28.
    Mohamadin AM, Habib FA, Elahi TF (2010) Serum paraoxonase 1 activity and oxidant/antioxidant status in Saudi women with polycystic ovary syndrome. Pathophysiology 17(3):189–196PubMedCrossRefGoogle Scholar
  29. 29.
    Torun AN, Vural M, Cece H, Camuzcuoglu H, Toy H, Aksoy N (2011) Paraoxonase-1 is not affected in polycystic ovary syndrome without metabolic syndrome and insülin resistance, but oxidative stress is altered. Gynecol Endocrinol 27(12):988–992PubMedCrossRefGoogle Scholar
  30. 30.
    Gupta N, Singh S, Maturu VN, Sharma YP, Gill KD (2011) Paraoxonase 1 (PON1) polymorphisms, haplotypes and activity in predicting CAD risk in North-West Indian Punjabis. PLoS One 6(5):e17805PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Taşkiran P, Cam SF, Sekuri C, Tüzün N, Alioğlu E, Altintaş N, Berdeli A (2009) The relationship between paraoxanase gene Leu-Met (55) and Gln-Arg (192) polymorphisms and coronary artery disease. Turk Kardiyol Dern Ars 37(7):473–478PubMedGoogle Scholar
  32. 32.
    Fortunato G, Rubba P, Panico S, Trono D, Tinto N, Mazzaccara C et al (2003) A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middleaged women. Atherosclerosis 167:141–148PubMedCrossRefGoogle Scholar
  33. 33.
    Regieli JJ, Jukema JW, Doevendans PA, Zwinderman AH, Kastelein JJ, Grobbee DE, van der Graaf Y (2009) Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention. J Am Coll Cardiol 54(14):1238–1245PubMedCrossRefGoogle Scholar
  34. 34.
    Balcerzyk A, Zak I, Krauze J (2007) Synergistic effects between Q192R polymorphism of paraoxonase 1 gene and some conventional risk factors in premature coronary artery disease. Arch Med Res 38(5):545–550PubMedCrossRefGoogle Scholar
  35. 35.
    Birjmohun RS, Vergeer M, Stroes ES, Sandhu MS, Ricketts SL, Tanck MW, Wareham NJ, Jukema JW, Kastelein JJ, Khaw KT, Boekholdt SM (2009) Both paraoxonase-1 genotype and activity do not predict the risk of future coronary artery disease; the EPIC-Norfolk prospective population study. PLoS One 4(8):e6809PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Mendonça MI, Dos Reis RP, Freitas AI, Sousa AC, Pereira A, Faria P, Gomes S, Silva B, Santos N, Serrão M, Ornelas I, Freitas S, Araújo JJ, Brehm A, Cardoso AA (2008) Human paraoxonase gene polymorphisms and coronary artery disease risk. Rev Port Cardiol 27(12):1539–1555PubMedGoogle Scholar
  37. 37.
    Likidlilid A, Akrawinthawong K, Poldee S, Sriratanasathavorn C (2010) Paraoxonase 1 polymorphisms as the risk factor of coronary heart disease in a Thai population. Acta Cardiol 65(6):681–691PubMedGoogle Scholar
  38. 38.
    Campo S, Sardo MA, Trimarchi G, Bonaiuto M, Castaldo M, Fontana L, Bonaiuto A, Bitto A, Saitta C, Saitta A (2004) The paraoxonase promoter polymorphism (−107)T > C is not associated with carotid intima-media thickness in Sicilian hypercholesterolemic patients. Clin Biochem 37(5):388–394PubMedCrossRefGoogle Scholar
  39. 39.
    Ehara S, Ueda M, Naruko T et al (2001) Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103:1955–1960PubMedCrossRefGoogle Scholar
  40. 40.
    San Millan JL, Corton M, Villuendas G, Sancho J, Peral B, Ascobar-Morreale HF (2004) Association of polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab 89:2640–2646PubMedCrossRefGoogle Scholar
  41. 41.
    San Millan JL, Alvarez-Blasco F, Luque-Ramirez M, Botella-Carretero JI, Ascobar-Morreale HF (2006) The PON1 −108C/T polymorphism, and not the polycystic ovary syndrome, is an important determinant of reduced serum paraoxonase activity in premenopausal women. Hum Reprod 21:3157–3161PubMedCrossRefGoogle Scholar
  42. 42.
    Zhang F, Liu HW, Fan P, Bai H, Song Q (2011) The −108 C/T polymorphism in paraoxonase 1 gene in Chinese patients with polycystic ovary syndrome. Sichuan Da Xue Xue Bao Yi Xue Ban 42(1):24–28PubMedGoogle Scholar
  43. 43.
    Wang Y, Liu H, Fan P, Bai H, Zhang J, Zhang F (2012) Evidence for association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome in southwest Chinese women. Eur J Endocrinol 166(5):877–885PubMedCrossRefGoogle Scholar
  44. 44.
    Lenarcik A, Bidzińska-Speichert B, Tworowska-Bardzińska U (2010) The role of chronic inflammation and Leu55Met PON1 polymorphism in the pathogenesis of polycystic ovary syndrome. Gynecol Endocrinol 26(9):673–683PubMedCrossRefGoogle Scholar
  45. 45.
    Nishi K, Itabe H, Uno M et al (2002) Oxidised LDL in carotid plaques and plasma associates with plaque instability. Arterioscler Thromb Vasc Biol 22:1649–1654PubMedCrossRefGoogle Scholar
  46. 46.
    Holvoet P, Van Cleemput J, Collen D, Vanhaecke J (2000) Oxidised low density lipoprotein is a prognostic marker of transplant-associated coronary artery disease. Arterioscler Thromb Vasc Biol 20:698–702PubMedCrossRefGoogle Scholar
  47. 47.
    Toshima S, Hasegawa A, Kurabayashi M, Itabe H, Takano T, Sugano J (2000) Circulating oxidised low density lipoproteins levels. Arterioscler Thromb Vasc Biol 20:2243–2247PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ayse Carlioglu
    • 1
  • Ikbal Kaygusuz
    • 2
    Email author
  • Feridun Karakurt
    • 3
  • Ilknur Inegol Gumus
    • 2
  • Aysel Uysal
    • 4
  • Benan Kasapoglu
    • 5
  • Ferah Armutcu
    • 6
  • Sema Uysal
    • 7
  • Esra Aktepe Keskin
    • 2
  • Cemile Koca
    • 8
  1. 1.Department of EndocrinologyRegional Education and Research HospitalErzurumTurkey
  2. 2.Department of Obstetrics and GynecologyTurgut Ozal University School of MedicineAnkaraTurkey
  3. 3.Department of EndocrinıologyGazi University Medical SchoolAnkaraTurkey
  4. 4.Department of Obstetrics and GynecologyEducation and Research HospitalAntalyaTurkey
  5. 5.Department of Internal MedicineTurgut Ozal University Medical SchoolAnkaraTurkey
  6. 6.Department of BiochemistryTurgut Ozal University Medical SchoolAnkaraTurkey
  7. 7.Department of BiochemistryNumune Education and Research HospitalAnkaraTurkey
  8. 8.Department of BiochemistryAtatürk Education and Research HospitalAnkaraTurkey

Personalised recommendations