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HİPERLİPİDEMİK HASTALARDA ATORVASTATİN TEDAVİSİNİN SERUM PARAOKSONAZ-1 DÜZEYİNE ETKİSİ

Effect of Atorvastatin Treatment on Serum Paraoxonase-1 Level in Hyperlipidemic Patients

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Abstract (2. Language): 
Introduction: Atherosclerosis-based diseases like coronary artery disease, myocardial infarction and stroke are leading causes of morbidity and mortality. Hyperlipidemia is among the major risk factors of atherosclerotic diseases and results in accelerated atherosclerosis. Paraoxonase-1 (PON1), an antioxidant enzyme, is reported to have a protective role in the atherosclerotic process, by contributing to the protective effect of HDL and preventing the oxidation of LDL cholesterol. Atorvastatin, a member of the class of statins, which are potent lipid-reducers, is widely used in hyperlipidemia. It was shown that PON1 level decreased in dyslipidemia. The studies on the effects of various lipid-reducing agents on PON 1 levels produced conflicting results. In the present study we aimed to examine the effect of atorvastatin treatment on serum PON1 level. Material and Methods: Sixty hyperlipidemic patients were treated with 10mg/day atorvastatin for 12 weeks. Serum lipids and PON1 levels were examined at the beginning of the study, in the first and third months and then, compared. Results: Twelve-week atorvastatin treatment brought about favorable changes in lipid profile, in consistency with the literature. Basal PON1 value was 186.94±40.13 (unit/L), whereas PON1 values were 205.60±44.79 (unit/L) in the first month and 226.00±40.15 (unit/L) in the third month. Serum PON1 value was observed to have statistically significantly increased in the third month, when compared to basal values. Conclusion: Atorvastatin treatment increases levels of PON1, which is reported to assume a protective role in atherosclerosis, in addition to producing positive changes in the lipid profile. ©2004, Fırat Üniversitesi, Tıp Fakültesi
Abstract (Original Language): 
Giriş: Koroner arter hastalığı, miyokard infarktüsü, inme gibi ateroskleroz temelli hastalıklar önde gelen morbidite ve mortalite sebepleridir. Hiperlipidemi aterosklerotik hastalıkların major risk faktörlerindendir ve hızlanmış ateroskleroz ile sonuçlanmaktadır. Antioksidan bir enzim olan Paraoksonaz-1'in (PON1), HDL'nin koruyucu etkisine katkıda bulunarak ve LDL kolesterolün oksidasyonunu önleyerek, aterosklerotik süreçte koruyucu bir role sahip olduğu bildirilmektedir. Potent lipid düşürücülerden statinlerin bir üyesi olan atorvastatin hiperlipidemide yaygın olarak kullanılmaktadır. PON1 düzeyinin, dislipidemide azaldığı ortaya konmuş ve çeşitli lipid düşürücü ajanların PON1 düzeylerine etkileri araştırılmıştır. Bu araştırmalarda çelişkili sonuçlar ortaya konmuştur. Bu çalışmada atorvastatin tedavisinin serum PON1 düzeyine etkisini araştırmayı amaçladık. Gereç ve Yöntem: 60 hiperlipidemik hasta 10 mg/gün atorvastatin ile 12 hafta süreyle tedavi edildi. Tedavinin başlangıcında, birinci ve üçüncü aylarında serum lipitleri ve PON1 düzeylerine bakıldı ve karşılaştırıldı. Bulgular: 12 haftalık atorvastatin tedavisi; lipid profilinde literatüre uygun olarak olumlu değişikliklere yol açtı. Ayrıca PON1 bazal değeri 186.94±40.13 (ünite/L) iken birinci ayda 205.60±44.79 (ünite/L) ve üçüncü ayda 226.00±40.15 (ünite/L) olarak saptandı. Serum PON1 düzeyinin üçüncü ayda bazal değerlere göre istatistiksel olarak anlamlı derecede arttığı gözlendi. Sonuç: Atorvastatin tedavisi lipit profilinde olumlu değişikliklere ilaveten aterosklerozda protektif rol üstlendiği bildirilen PON1 düzeylerinde artışa yol açmaktadır. ©2004, Fırat Üniversitesi, Tıp Fakültesi
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REFERENCES

References: 

1. Ford ES, Giles WH, Mokdad AH. The distribution of 10-Year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol 2004; 43: 1791-1796.
2. Rosenson RS. Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis. 2004; 173: 1-12.
3. Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001; 37: 1053¬1059.
125
Fırat Tıp Dergisi 2004;9(4): 123-126
4. Groop L, Orho-Melander M. The dysmetabolic syndrome. Intern Med. 2001; 250: 105-120.
5. Tokgözoğulu L, Özer N. Ateroskleroz patogenezi. Özcan N. Koroner kalp hastalıkları. 1. Baskı. Ankara 1997. 129-163.
6. Gordon DJ, Probstfeld JL, Garrison RJ. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American study. Circulation 1989; 37: 47-53.
7. Mackness B, Durrington PN, Mackness MI. Human serum paraoxonase. Gen Pharmacol. 1998; 31: 329-336.
8. Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol. 2001; 21: 473-80.
9. Mackness MI, Mackness B, Durrington PN. Paraoxonase and coronary heart disease. Atheroscler Suppl. 2002; 3: 49-55.
10. Aviram M. Does paraoxonase play a role in susceptibility to cardiovascular disease? Mol Med Today. 1999; 5: 381-386.
11. Kwak BR, Mulhaupt F, Mach F. Atherosclerosis: anti-inflammatory and immunomodulatory activities of statins.
Autoimmun Rev. 2003; 2: 332-338.
12. Blumenthal RS. Statins: effective antiatherosclerotic therapy. Am. Heart J. 2000; 139: 577-583.
13. Kudchodkar BJ, Lacko AG, Dory L, Fungwe TV. Dietary fat modulates serum paraoxonase 1 activity in rats. J Nutr. 2000; 130:
2427-33.
14. Williams FM, Elaine N, Blain PG. Paraoxonase distribution in Caucasian males. Clin Biol Interactions 1993; 87: 155-160.
15. Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA. Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol. 1996; 7: 69-76.
16. Sutherland WHF, Walker RJ, Jong SA, Van Rij AM. Reduced
postprandial serum paraoxonase activity after a meal rich in used cooking fat. Arteroscler Thromb Vasc Biol 1999; 19: 1340-1347.
17. Mackness MI, Harty D, Bhatnagar D, Winocour PH, Arrol S, Ishola M, Durrington PN. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus. Atherosclerosis. 1991; 86:193-199.
18. Mackness MI, Arrol S, Abbot CA, Durrington PN. Is paraoxonase related to atherosclerosis? Chem Biol Interactions 1993; 87: 161¬171.
Özkan
v
e Ark.
19. Rengström J, Nilsson J, Tornvall P, Landou C, Hamsten A. Susceptibility to LDL oxidation and coronary atherosclerosis in man. Lancet 1992; 339:1183-1186.
20. Watson AD, Berliner JA, Hama SY, et al. Protective effect of HDL associated paraoxonase inhibition of the biological activity of minimally oxidized LDL. J Clin Invest. 1995; 96: 2882-2891.
21. Navab M, Hama-Levy S, Van Lenten BJ, et al. Oxidized LDL induces an increased apolipoprotein J/PON ratio. J Clin Invest.
1997; 99: 2005-19.
22. Aviram M, Rosenblot M, Bisgaier CL, et al. Paraoxonase inhibits high density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Cin Invest. 1998; 101: 1581-1590.
23. Fuhrman B, Koren L, Volkona N, Keidar S. Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis 2002;
164: 179-185.
24. Tomas M, Senti M, Faria GF Vila J. Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2000; 20: 2113-2119.
25. Balogh Z, Seres I, Harangi M, et al. Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates? Diabetes Metab. 2001; 27: 604¬610.
26. Harangi M, Seres I, Varga Z, et al. Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage. Eur J Clin Pharmacol. 2004; 60:685-691.
27. Paragh G, Torocsik D, Seres I, et al. Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia. Curr Med Res Opin. 2004; 20: 1321-1327.
28. Beltowski J, Wojcicka G, Jamroz A. Differential effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on plasma paraoxonase 1 activity in the rat. Pol J Pharmacol. 2002; 54: 661-671.
29. Durrington PN, Mackness MI, Bhatnagar D, et al. Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia.
Atherosclerosis. 1998; 138: 217-25.

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