Abstract
Atherosclerosis is one of the leading causes of death in Western countries, with high-density lipoproteins (HDL) playing an important protective role due to their ability to inhibit oxidation of low-density lipoproteins (LDL), thus relieving vascular subendothelial damage. One of the proteins constituting HDL particles is paraoxonase-1 (PON1), an enzyme able to hydrolyze aryl esters, lactones, and organophosphates. Other closely related paraoxonases are designated as PON2, which is a protein localized inside many different kinds of cells, and PON3, not only present in HDL but also in mitochondria and endoplasmic reticulum, as well. Given that the amount and the activity of PON1 in human serum are significantly lower in people suffering from cardiovascular diseases, enhancing both parameters might contribute to their treatment and prevention. One of the physiologically interesting substrates for the abovementioned hydrolytic cleavage is homocysteine thiolactone (HTL), an atherothrombotic active form of homocysteine. Although it was therefore postulated that PON1 would participate in preventing the HTL-mediated lipid peroxidation, some attention is recently paid to other enzymes, like biphenyl hydrolase-like protein, that seem to more selectively involved in lowering this risk factor. The aim of this paper is to elucidate the role of paraoxonases, especially PON1, by reviewing the latest studies in order to understand both its physiological role and modulation by drugs, nutrients, and plant extracts.
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Ackerman Z, Oron-Herman M, Pappo O et al (2010) Hepatic effects of rosiglitazone in rats with the metabolic syndrome. Basic Clin Pharmacol Toxicol 107(2):663–668. https://doi.org/10.1111/j.1742-7843.2010.00553.x
Ahmad S, Carter JJ, Scott JE (2010) A homogeneous cell-based assay for measurement of endogenous paraoxonase 1 activity. Anal Biochem 400(1):1–9. https://doi.org/10.1016/j.ab.2010.01.023
Akalin Çiftçi G, Ertorun I, Akalin A et al (2015) The effects of atorvastatin on antioxidant/antiinflammatory properties of HDLs in hypercholesterolemics. Turk J Med Sci 45(11):345–351. https://doi.org/10.1194/jlr.M600297-JLR200
Altenhöfer S, Witte I, Teiber JF et al (2010) One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity. J Biol Chem 285(32):24398–243403. https://doi.org/10.1074/jbc.M110.118604
Aviram M, Hardak E, Vaya J et al (2000) Human serum paraoxonase (PON) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 101(21):2510–2517. https://doi.org/10.1161/01.CIR.101.21.2510
Aviram M, Volkova N, Coleman R et al (2008) Pomegranate phenolics from the peels, arils, and flower are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein E-deficient (Eo) mice and in vitro in cultured macrophages and lipoproteins. J Agric Food Chem 56(3):1148–1157. https://doi.org/10.1021/jf071811q
Bajaj P, Aggarwal G, Tripathy RK, Pande AH (2014) Interplay between amino acid residues at positions 192 and 115 in modulating hydrolytic activities of human paraoxonase 1. Biochimie 105:202–210. https://doi.org/10.1016/j.biochi.2014.07.024
Balogh Z, Seres I, Harangi M et al (2001) Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates? Diabetes Metab 27:604–610. DM-11-2001-27-5-1262-3636-101019-ART10
Bhattacharyya T, Nicholls SJ, Topol EJ et al (2008) Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. J Am Med Assoc 299(11):1265–1276. https://doi.org/10.1001/jama.299.11.1265
Boesch-Saadatmandi C, Egert S, Schrader C et al (2010) Effect of quercetin on paraoxonase 1 activity—studies in cultured cells, mice and humans. J Physiol Pharmacol 61:99–105. No doi available.
Bouman HJ, Schömig E, van Werkum JW et al (2011) Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med 17(1):110–116. https://doi.org/10.1038/nm.2281
Cakmak A, Zeyrek D, Atas A, Erel O (2010) Paraoxonase activity in athletic adolescents. Pediatr Exerc Sci 22(1):93–104. https://doi.org/10.1123/pes.22.1.93
Camps J, Marsillach J, Joven J (2007) Measurement of serum paraoxonase-1 activity as a potential biomarker for chronic liver impairment. Clin Chim Acta 386(1-2):114–115. https://doi.org/10.1016/j.cca.2007.07.016
Charles-Schoeman C, Gonzalez-Gay MA, Kaplan I, Boy M, Geier J, Luo Z, Zuckerman A, Riese R (2016) Effects of tofacitinib and other DMARDs on lipid profiles in rheumatoid arthritis: implications for the rheumatologist. Semin Arthritis Rheum 46(1):71–80. https://doi.org/10.1016/j.semarthrit.2016.03.004
Chithra PK, Sindhu G, Shalini V et al (2015) Dietary Njavara rice bran oil reduces experimentally induced hypercholesterolaemia by regulating genes involved in lipid metabolism. Br J Nutr 113(08):1207–1219. https://doi.org/10.1017/S0007114515000513
Cole TB, Jampsa RL, Walter BJ et al (2003) Expression of human paraoxonase (PON1) during development. Pharmacogenetics 13(6):357–364. https://doi.org/10.1097/00008571-200306000-00007
Cooney M, Dudina A, De Bacquer D et al (2009) HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk. Atherosclerosis 206:611–616. https://doi.org/10.1016/j.atherosclerosis.2009.02.04123
Costa L, Giordano G, Furlong G (2011) Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression. The hunt goes on. Biochem Pharmacol 81(3):337–344. https://doi.org/10.1016/j.bcp.2010.11.008
Dansette PM, Rosi J, Bertho G, Mansuy D (2011) Paraoxonase-1 and clopidogrel efficacy. Nat Med 17(9):1040–1041. https://doi.org/10.1038/nm.2436
Dansette PM, Rosi J, Bertho G, Mansuy D (2012) Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer. Chem Res Toxicol 25(2):348–356. https://doi.org/10.1021/tx2004085
Deakin SP, James RW (2004) Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci 107(5):435–447. https://doi.org/10.1042/CS20040187
Deakin S, Leviev I, Gomaraschi M et al (2002) Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 277:4301–4308. https://doi.org/10.1074/jbc.M107440200.
Derosa G, Mugellini A, Pesce RM et al (2016) Olmesartan combined with amlodipine on oxidative stress parameters in type 2 diabetics, compared with single therapies: a randomized, controlled, clinical trial. Medicine (Baltimore) 95:e3084. https://doi.org/10.1097/MD.0000000000003084.
Di Santolo M, Bnafi G, Stel G, Cauci S (2009) Association of recreational physical activity with homocysteine, folate and lipid markers in young men. Eur J Appl Physiol 105(1):111–118. https://doi.org/10.1007/s00421-008-0880-x
Draganov DI, La Du BN (2004) Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedeberg's Arch Pharmacol 369(1):78–88. https://doi.org/10.1007/s00210-003-0833-1
Durand P, Prost M, Loreau N et al (2001) Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 81(5):645–672. https://doi.org/10.1038/labinvest.3780275
Durrington PN, Mackness MI, Bhatnagar D, Julier K, Prais H, Arrol S, Morgan J, Wood GNI (1998) Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia. Atherosclerosis 138(1):217–225. https://doi.org/10.1016/S0021-9150(98)00003-3
Ekinci D, Beydemir S (2009) Purification of PON1 from human serum and assessment of enzyme kinetics against metal toxicity. Biol Trace Elem Res 135(1-3):112–120. https://doi.org/10.1007/s12011-009-8500-0
El-Sayed YS, Lebda MA, Hassinin M, Neoman SA (2015) Chicory (Cichorium intybus L.) root extract regulates the oxidative status and antioxidant gene transcripts in CCl4-induced hepatotoxicity. PLoS One 10(3):e0121549. https://doi.org/10.1371/journal.pone.0121549
El-Tantawy WH (2015) Biochemical effects, hypolipidemic and anti-inflammatory activities of Artemisia vulgaris extract in hypercholesterolemic rats. J Clin Biochem Nutr 57(1):33–38. https://doi.org/10.3164/jcbn.14-141
Farrell N, Norris G, Lee SG et al (2015) Anthocyanin-rich black elderberry extract improves markers of HDL function and reduces aortic cholesterol in hyperlipidemic mice. Food Funct 6(4):1278–1287. https://doi.org/10.1039/c4fo01036a
Ferré N, Camps J, Fernández-Ballart J et al (2003) Regulation of serum paraoxonase activity by genetic, nutritional and lifestyle factors in the general population. Clin Chem 49(9):1491–1497. https://doi.org/10.1373/49.9.1491
Ferretti G, Bacchetti T, Masciangelo S, Bicchiega V (2010) HDL-paraoxonase and membrane lipid peroxidation: a comparison between healthy and obese subjects. Obesity 18(6):1079–1084. https://doi.org/10.1038/oby.2009.338
Ferretti G, Bacchetti T, Sahebkar A (2015) Effect of statin therapy on paraoxonase-1 status: a systematic review and meta-analysis of 25 clinical trials. Prog Lipid Res 60:50–73. https://doi.org/10.1016/j.plipres.2015.08.003
Furlong CE, Marsillach J, Jarvik GP, Costa LG (2016) Paraoxonases-1, -2 and -3: what are their functions? Chem Biol Interact 259(Pt B):51–62. https://doi.org/10.1016/j.cbi.2016.05.036
Gaidukov L, Rosenblat M, Aviram M, Tawfik DS (2006) The 192R/Q polymorphism of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholestrol efflux. J Lipid Res 14(11):2492–2502. https://doi.org/10.1194/jlr.M600297-JLR200
Garige M, Gong M, Varatharajalu R, Lakshman MR (2010) Quercetin up-regulates paraoxonase 1 gene expression via sterol regulatory element binding protein 2 that translocates from the endoplasmic reticulum to the nucleus where it specifically interacts with sterol responsive element-like sequence in paraoxonase 1 promoter in HuH7 liver cells. Metab Clin Exp 59(9):1372–1378. https://doi.org/10.1016/j.metabol.2009.12.025
Gong M, Garige M, Varatharajalu R et al (2009) Quercetin up-regulates paraoxonase 1 gene expression with concomitant protection against LDL oxidation. Biochem Biophys Res Commun 379(4):1001–1004. https://doi.org/10.1016/j.bbrc.2009.01.015
Gordon SM, Hofmann S, Askew DS, Davidson WS (2011) High density lipoprotein it's not just about lipid transport anymore. Trends Endocrinol Metab 22(1):9–15. https://doi.org/10.1016/j.tem.2010.10.001
Gouédard C, Korum-Besson N, Barouki R, Morel Y (2003) Opposite regulation of the human paraoxonase-1 gene PON-1 by fenofibrate and statins. Mol Pharmacol 63(4):945–956. https://doi.org/10.1124/mol.63.4.945
Guney T, Alisik M, Alkan A et al (2016) Paraoxonase and arylesterase activities in adults with B12 deficiency. Redox Rep 21(1):1–5. https://doi.org/10.1179/1351000215Y.0000000042
Guo YS, Wang CX, Cao J, Gao JL, Zou X, Ren YH, Fan L (2015) Antioxidant and lipid-regulating effects of probucol combined with atorvastatin in patients with acute coronary syndrome. J Thorac Dis 7(3):368–375. https://doi.org/10.3978/j.issn.2072-1439.2014.12.29
Horke S, Witte I, Wilgenbus P et al (2007) Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation. Circulation 115(15):2055–2064. https://doi.org/10.1161/CIRCULATIONAHA.106.681700
Huang TW, Chang CL, Kao ES, Lin JH (2015) Effect of Hibiscus sabdariffa extract on high fat diet-induced obesity and liver damage in hamsters. Food Nutr Res 59:29018. https://doi.org/10.3402/fnr.v59.29018
Hussein O, Zidan J, Abu Jabal K et al (2012) Paraoxonase activity and expression is modulated by therapeutics in experimental rat nonalcoholic fatty liver disease. Int J Hepatol 2012:265305. https://doi.org/10.1155/2012/265305
Jaichander P, Selvarajan K, Garelnabi M, Parthasarathy S (2008) Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res 49(10):2142–2148. https://doi.org/10.1194/jlr.M800082-JLR200
Jarvik GP, Tsai NT, Mckinstry LA et al (2002) Vitamins C and E intake is associated with increased paraoxonase activity. Arterioscler Thromb Vasc Biol 22(8):1329–1333. https://doi.org/10.1161/01.ATV.0000027101.40323.3A
Kim DS, Burt AA, Ranchalis JE et al (2012) Dietary cholesterol increases paraoxonase 1 enzyme activity. J Lipid Res 53(11):2450–2458. https://doi.org/10.1194/jlr.P030601
Kiranoglu S, Sinan S, Gencer N et al (2007) In vivo effects of oral contraceptives on paraoxonasae, catalase and carbonic anhydrase enzymes activities on mouse. Biol Pharm Bull 30(6):1048–1051. https://doi.org/10.1248/bpb.30.1048
Koc A, Cengiz M, Ozdemir ZC, Celik H (2012) Paraoxonase and arylesterase activities in children with iron deficiency anemia and vitamin B12 deficiency anemia. Pediatr Hematol Oncol 29(4):345–353. https://doi.org/10.3109/08880018.2011.645185
Koren-Gluzer M, Aviram M, Meilin E, Hayek T (2011) The antioxidant HDL-associated paraoxonase-1 (PON1) attenuates diabetes development and stimulates β-cell insulin release. Atherosclerosis 213(2):510–518. https://doi.org/10.1016/j.atherosclerosis.2011.07.119
Kotani K, Tsuzaki K, Sakane NK (2012) Paraoxonase-1 gene Q192R polymorphism and reactive oxygen metabolites. J Int Med Res 40(4):1513–1518. https://doi.org/10.1177/147323001204000431
Kurban S, Mehmetoglu I (2010) Effects of acetylsalicylic acid on serum paraoxonase activity, Ox-LDL, coenzyme Q10 and other oxidative stress markers in healthy volunteers. Clin Biochem 43(3):287–290. https://doi.org/10.1016/j.clinbiochem.2009.10.054
Lawrence de Koning AB, Werstuck GH, Zhou J, Austin RC (2003) Hyperhomocysteinemia and its role in the development of atherosclerosis. Clin Biochem 36(6):431–441. https://doi.org/10.1016/S0009-9120(03)00062-6
Li X, Zhang L, Chen X et al (2013) PON1 Q192R genotype influences clopidogrel responsiveness by relative platelet inhibition instead of on-treatment platelet reactivity. Thromb Res 132(4):444–449. https://doi.org/10.1016/j.thromres.2013.08.004
Macan M, Vukšić A, Žunec S et al (2015) Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats. Pharmacol Rep 67(5):907–913. https://doi.org/10.1016/j.pharep.2015.02.005
MacKness B, MacKness M (2010) Anti-inflammatory properties of paraoxonase-1 in atherosclerosis. Adv Exp Med Biol 660:143–151. https://doi.org/10.1007/978-1-60761-350-3_13
Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN (1998) Effect of the human serum paraoxonase 55 and 192 genetic polymorphimsms on the protection by high density lipoprotein against low density lipoprotein oxidative modificaction. FEBS Lett 423(1):57–56. https://doi.org/10.1016/S0014-5793(98)00064-7
Marsillach J, Ferré N, Vila MC et al (2007) Serum paraoxonase-1 in chronic alcoholics: relationship with liver disease. Clin Biochem 40(9-10):645–650. https://doi.org/10.1016/j.clinbiochem.2007.01.020
Marsillach J, Suzuki SM, Richter RJ et al (2014) Human valacyclovir hydrolase/biphenyl hydrolase-like protein is a highly efficient homocysteine thiolactonase. PLoS One 9(10):e110054. https://doi.org/10.1371/journal.pone.0110054
McInnes I, Kaplan I, Boy M et al (2013) Effects of tofacitinib on lipid biomarkers in patients with active rheumatoid arthritis. Ann Rheum Dis 72, Suppl 3:416. doi:https://doi.org/10.1136/annrheumdis-2013-eular.1264, Suppl 3, A4A416.
Milnerowicz H, Kowalska K, Socha E (2015) Paraoxonase activity as a marker of exposure to xenobiotics in tobacco smoke. Int J Toxicol 34(3):224–232. https://doi.org/10.1177/1091581815584624
Mohammadi E, Rafraf M (2012) Benefits of omega-3 fatty acids supplementation on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Health Promot Perspect 2(2):197–204. https://doi.org/10.5681/hpp.2012.023
Navab M, Hama-Levy S, Van Lenten BJ et al (1997) Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest 99(8):2005–2019. https://doi.org/10.1172/JCI119369
Nguyen SD, Hung ND, Cheon-Ho P, Ree KM, Dai-Eun S (2009) Oxidative inactivation of lactonase activity of purified human paraoxonase 1 (PON1). Biochim Biophys Acta 1790(3):155–160. https://doi.org/10.1016/j.bbagen.2008.11.009
Nguyen SD, Sok DE (2003) Beneficial effect of oleoyated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization. Biochem J 375(2):275–285. https://doi.org/10.1042/BJ20030663
Nishio R, Shinke T, Otake H et al (2013) Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss of functions carriers. Thromb Res 132(5):558–564. https://doi.org/10.1016/j.thromres.2013.09.008
Nishio E, Watanabe Y (1997) Cigarette smoke extract inhibits plasma paraoxonase activity by modification of the enzyme's free thiols. Biochem Biophys Res Commun 236(2):289–293. https://doi.org/10.1006/bbrc.1997.6961
Noll C, Hamelet J, Matulewicz E, Paul JL, Delabar JM, Janel N (2009) Effects of red wine polyphenolic compounds on paraoxonase-1 and lecitin like oxidized low density lipoprotein receptor-1 in hyperhomocysteinemic mice. J Nutr Biochem 20(8):586–596. https://doi.org/10.1016/j.jnutbio.2008.06.002
Otocka-Kmiecik A, Lewandowski M, Stolarek R et al (2010) Effect of single bout of maximal exercise on plasma antioxidant status and paraoxonase activity in young sportmen. Redox Rep 15(6):275–281. https://doi.org/10.1179/135100010X12826446921905
Phuntuwate W, Suthisisang C, Koanantukul B et al (2008) Effect of fenofibrate therapy on paraoxonase 1 status in patients with low HDL-C levels. Atherosclerosis 196(1):122–128. https://doi.org/10.1016/j.atherosclerosis.2007.03.001
Rafraf M, Bazyun B, Sarabchian MA et al (2016) Vitamin E improves serum paraoxonase-1 activity and some metabolic factors in patients with type 2 diabetes: no effects on nitrite/nitrate levels. J Am Coll Nutr 17(6):1–8. https://doi.org/10.1080/07315724.2015.1116896
Rainwater DL (2005) Determinants of variation in serum paraoxonase enzyme activity in baboons. J Lipid Res 46(7):1450–1456. https://doi.org/10.1194/jlr.M400473-JLR200
Rao MN, Marmillot P, Gong M et al (2003) Light, but not heavy alcohol drinking, stimulates paraoxonase by upregulating liver mRNA in rats and humans. Metab Clin Exp 52(10):1287–1294. https://doi.org/10.1016/S0026-0495(03)00191-4
Rock W, Rosenblat M, Miller-Lotan R et al (2008) Consumtion of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and simulates its catalytic activities. J Agric Food Chem 56(18):8704–8713. https://doi.org/10.1021/jf801756x
Rom O, Aviram M (2016) Paraoxsonase2 (PON2) and oxidative stress involvement in pomegranate juice protection against cigarette smoke-induced macrophage cholesterol accumulation. Chem Biol Interact 259(Pt B):394–400. https://doi.org/10.1016/j.cbi.2016.05.00
Rosenblat M, Gaidukov L, Khersonsky O et al (2006) The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux. J Biol Chem 281(11):7657–7665. https://doi.org/10.1074/jbc.M512595200
Rosenblat M, Volkova N, Borochov-Neori H et al (2015) Anti-atherogenic properties of date vs. pomegranate polyphenols: the benefits of the combination. Food Funct 6(5):1496–1509. https://doi.org/10.1039/c4fo00998c
Rozenberg O, Shih DM, Aviram M (2003) Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: possible role for its phospholipase-A2 like activity and lysophosphatidylcholine formation. Arterioscler Thromb Vasc Biol 23(3):461–467. https://doi.org/10.1161/01.ATV.0000060462.35946.B3
Sacan O, Turkyilmaz IB, Mutlu O et al (2016) Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats. Biometals 29(2):239–248. https://doi.org/10.1007/s10534-016-9911-y
Sarandol E, Dirican M, Ocak N et al (2010) The effects of vitamin E coated dialysis membranes on serum paraoxonase activity in hemodialysis patients. J Nephrol 23:431–437. No doi available.
Sentí M, Tomás M, Anglada R et al (2003) Inter-relationship of smoking, paraoxonase activity, and leisure time physical activity: a population-based study. Eur. J Int Med 14(3):178–184. https://doi.org/10.1016/S0953-6205(03)00041-4
Shidfar F, Amani S, Vafa M et al (2016) Effects of iron supplementation with and without docosahexaenoic acid on the cardiovascular disease risk based on paraoxonase-1, Hs-CRP, and ApoB/ApoA-1 ratio in women with iron deficiency anemia. Biol Trace Elem Res 169(1):34–40. https://doi.org/10.1007/s12011-015-0383-7
Shih DM, Xia YR, Yu JM, Lusis AJ (2010) Temporal and tissue-specific patterns of PON3 expression in mouse: in situ hybridization analysis. Adv Exp Med Biol 660:73–87. https://doi.org/10.1007/978-1-60761-350-3_8
Stevens RC, Suzuki SM, Cole TB, Park SS, Richter RJ, Furlong CE (2008) Engineered recombinant human paraoxonase 1 (rHuPON1) purified from Escherichia coli protects against organophosphate poisoning. Proc Natl Acad Sci U S A 105(35):12780–12784. https://doi.org/10.1073/pnas.0805865105
Suszynska J, Tisonczyk J, Lee HG et al (2010) Reduced homocysteine-thiolactonase activity in Alzheimer's disease. J Alzheimers Dis 19(4):1177–1183. https://doi.org/10.3233/JAD-2010-1311
Tas S, Sarandol E, Ziyanok S et al (2005) Effects of green tea on serum paraoxonase/arylesterase activities in streptozotocin-induced diabetic rats. Nutr Res 25(12):1061–1074. https://doi.org/10.1016/j.nutres.2005.10.001
Taylan M, Kaya H, Demir M et al (2016) The protective effects of caffeic acid phenethyl ester on acetylsalicylic acid-induced lung injury in rats. J Invest Surg 29(6):328–334. https://doi.org/10.3109/08941939.2016.1149641
Tomás M, Sentí M, Elosúa R et al (2001) Interaction between Gln-Arg 192 variants of the paraoxonase gene and oleic acid intake as a determinant of high density lipoprotein cholesterol and paraoxonase activity. Eur J Pharmacol 432(2-3):121–128. https://doi.org/10.1016/S0014-2999(01)01482-0
Tsakiris S, Karikas GA, Parthimos T (2009) Interaction between Gln-Arg 192 variants of α-tocopherol supplementation prevents the exercise-induced reduction of serum paraoxonase 1/arylesterase activities in healthy individuals. Eur J Clin Nutr 63(2):215–221. https://doi.org/10.1038/sj.ejcn.1602918
Turfaner N, Uzun H, Blaci H et al (2010) Ezetimibe therapy and its influence on oxidative stress and fibrinolytic activity. South Med J 103:428–433. https://doi.org/10.1097/SMJ.0b013e3181d83374.doi:10.1097/SMJ.0b013e3181d83374
Ustundag B, Bahcecioglu IH, Sahin K, Duzgun S, Koca S, Gulcu F, Ozercan IH (2007) Protective role of soy isoflavones and activity levels of plasmas paraoxonase and arylesterase in the experimental nonalcoholic steatohepatitis model. Dig Dis Sci 52(8):2006–2014. https://doi.org/10.1007/s10620-006-9251-9
van Wijk J, Coll B, Cabezas MC et al (2006) Rosiglitazone modulates fasting and post-prandial paraoxonase 1 activity in type 2 diabetic patient. Clin Exp Pharmacol Physiol 33(12):1134–1137. https://doi.org/10.1111/j.1440-1681.2006.04505.x
Wang ZY, Chen M, Zhu LL et al (2015) Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy. Ther Clin Risk Manag 19:449–467. https://doi.org/10.2147/TCRM.S80437
Weijun G, Juming L, Guoqing Y et al (2008) Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes. Adv Ther 25(9):884–893. https://doi.org/10.1007/s12325-008-0095-x
Wójcicka G, Jamroz-Wiśniewska A, Marciniak A et al (2010) The differentiating effect of glimepiride and glibenclamide on paraoxonase 1 and platelet-activating factor acetylohydrolase activity. Life Sci 87(3-4):126–132. https://doi.org/10.1016/j.lfs.2010.05.018
Yamashita J, Iwamura C, Ito T et al (2013) Paraoxonase-1 suppresses experimental colitis via the inhibition of IFN-γ production from CD4 T cells. J Immunol 191(2):949–960. https://doi.org/10.4049/jimmunol.1201828
Yehuda I, Madar Z, Leikin-Frenkel A et al (2016) Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation. Mol Nutr Food Res 60:287–299. https://doi.org/10.1002/mnfr.201500441.
Yildiz A, Gul CB, Ocak N et al (2015) Fluvastatin decreases oxidative stress in kidney transplant patients. Transplant Proc 47(10):2870–2874. https://doi.org/10.1016/j.transproceed.2015.10.027
Zhao Y, Ma Y, Fang Y et al (2012) Association between PON1 activity and coronary heart disease risk: a meta-analysis based on 43 studies. Mol Genet Metab 105(1):141–148. https://doi.org/10.1016/j.ymgme.2011.09.018
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Moya, C., Máñez, S. Paraoxonases: metabolic role and pharmacological projection. Naunyn-Schmiedeberg's Arch Pharmacol 391, 349–359 (2018). https://doi.org/10.1007/s00210-018-1473-9
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DOI: https://doi.org/10.1007/s00210-018-1473-9