Seres I


Full name : Seres Ildiko

First name : Ildiko

Mail : First Department of Medicine, University of Debrecen, Medical and Health Science Center,Nagyerdei krt. 98, 4032 Debrecen

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Country : Hungary

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References (44)

Title : Assessment of amino-terminal C-type natriuretic peptide serum level and its correlation with high-density lipoprotein structure and function in patients with end stage renal disease before and after kidney transplantation - Szentimrei_2023_Chem.Biol.Interact_14ChEPon_385_110749
Author(s) : Szentimrei R , Lorincz H , Szentpeteri A , Varga VE , Seres I , Varga , Nemes B , Harangi M , Paragh G
Ref : Chemico-Biological Interactions , 385 :110749 , 2023
Abstract : We aimed to investigate serum amino-terminal C-type natriuretic peptide (NT-proCNP) and its relationship with quantitative and qualitative HDL-parameters in patients with end-stage renal disease (ESRD) before, then 1 and 6 months after kidney transplantation (TX). Seventy patients (47 males, 23 females, mean age 51.7 +/- 12.4 years) were enrolled in a prospective follow-up study. We examined serum creatinine, C-reactive protein, procalcitonin, fasting glucose and lipid parameters before, then 1 and 6 months after TX. High-density lipoprotein- (HDL)-associated paraoxonase-1 (PON1) paraoxonase and arylesterase activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. NT-proCNP and oxidized low-density lipoprotein (oxLDL) levels were measured by ELISA. Mean NT-proCNP was 45.8 +/- 21.9 pmol/L before renal transplantation and decreased markedly 1 month and 6 months after transplantation (5.3 +/- 2.5 and 7.7 +/- 4.9 pmol/L, respectively, P = 1 x 10(-4)). During the 6 months' follow-up, PON1 arylesterase, paraoxonase and salt-stimulated paraoxonase activities improved. NT-proCNP positively correlated with procalcitonin and creatinine and negatively with GFR, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C). There was a negative correlation between serum NT-proCNP and PON1 arylesterase activity. According to the multiple regression analysis, the best predicting variables of NT-proCNP were serum procalcitonin, creatinine and PON1 arylesterase activity. NT-proCNP might be a novel link between HDL dysfunction and impaired vascular function in ESRD, but not after kidney transplantation. Further studies in larger populations are needed to clarify the exact role of NT-proCNP in the risk prediction for cardiovascular comorbidities and complications in ESRD.
ESTHER : Szentimrei_2023_Chem.Biol.Interact_14ChEPon_385_110749
PubMedSearch : Szentimrei_2023_Chem.Biol.Interact_14ChEPon_385_110749
PubMedID: 37802408

Title : High-density lipopoprotein antioxidant capacity, subpopulation distribution and paraoxonase-1 activity in patients with systemic lupus erythematosus - Gaal_2016_Lipids.Health.Dis_15_60
Author(s) : Gaal K , Tarr T , Lorincz H , Borbas V , Seres I , Harangi M , Fulop P , Paragh G
Ref : Lipids Health Dis , 15 :60 , 2016
Abstract : BACKGROUND: The causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients.
METHODS: Lipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined.
RESULTS: HDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 +/- 26.87 vs. 148.35 +/- 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 +/- 58.28 % vs. 217.71 +/- 54.36 %, p < 0.001) were significantly reduced in patients compared to controls. Additionally, all HDL subfraction concentrations were significantly decreased in patients, while the levels of the examined inflammatory markers were significantly elevated in SLE subjects. The latter correlated positively with disease activity, and negatively with HDL concentration and total HDL antioxidant capacity, respectively. PON1 arylesterase activity and erythrocyte sedimentation rate were independent predictors of total HDL antioxidant capacity.
CONCLUSIONS: Induced by the systemic inflammation, altered composition and antioxidant activity may diminish the anti-atherogenic effect of HDL and therefore may contribute to the increased cardiovascular risk of SLE patients.
ESTHER : Gaal_2016_Lipids.Health.Dis_15_60
PubMedSearch : Gaal_2016_Lipids.Health.Dis_15_60
PubMedID: 27004558

Title : Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications - Zsiros_2016_Clin.Biochem_49_862
Author(s) : Zsiros N , Koncsos P , Lorincz H , Seres I , Katko M , Szentpeteri A , Varga VE , Fulop P , Paragh G , Harangi M
Ref : Clinical Biochemistry , 49 :862 , 2016
Abstract : OBJECTIVES: Myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were shown to contribute to atherogenesis, while human paraoxonase-1 (PON1) protects against oxidative stress. Although several studies investigated these biomarkers, their associations have not been completely clarified yet. We aimed to investigate these parameters in overweight hyperlipidemic, lipid-lowering therapy-naive patients (n=167) with and without vascular complications. DESIGN AND
METHODS: MPO, MMP-9 and TIMP-1 levels were measured by ELISA. PON1 activities were detected spectrophotometrically. PON1 phenotype was calculated by using a dual substrate method.
RESULTS: Patients with vascular complications (VC) had significantly higher MPO and TIMP-1 levels compared to those without (patients with no vascular complications; NVC) (728 (367.25-1177.90) mg/ml vs. 315.9 (176.05-687.40) mg/ml; p<0.001; and 172.7 (157.7-197.7) ng/ml vs. 152.6 (129.3-172.3) ng/ml; p<0.0001; respectively). MPO levels showed a significant negative correlation with PON1 arylesterase activity (whole patient group (W): r=0.42, p<0.0001; VC: r=0.44, p=0.01; NVC: r=0.39, p<0.0001) and positive correlations with MMP-9 (W: r=0.37, p<0.0001; VC: r=0.29, p=0.07; NVC: r=0.42, p<0.0001) and TIMP-1 (W: r=0.42, p<0.0001; VC: r=0.33, p<0.05; NVC: r=0.41, p<0.0001), respectively. PON1 arylesterase activity was found to be an independent predictor of MPO levels in the whole patient group (beta=-0.350, p<0.0001) or when studied separately in the subgroups with or without cardiovascular complications (VC: beta=-0.57, p<0.05; NVC: beta=-0.33, p<0.0001).
CONCLUSIONS: Our results suggest that parallel investigation of MPO, MMP-9 and TIMP-1 levels and PON1 arylesterase activity may be a more accurate indicator of atherosclerosis, which may allow earlier treatment and therefore, improvement of treatment efficacy.
ESTHER : Zsiros_2016_Clin.Biochem_49_862
PubMedSearch : Zsiros_2016_Clin.Biochem_49_862
PubMedID: 27129797

Title : Paraoxonase-1 and adipokines: potential links between obesity and atherosclerosis - Fulop_2016_Chem.Biol.Interact_259_388
Author(s) : Fulop P , Harangi M , Seres I , Paragh G
Ref : Chemico-Biological Interactions , 259 :388 , 2016
Abstract : Oxidative stress and chronic low-grade inflammation are major characteristics of obesity-related disorders. The dominance of pro-oxidant and pro-inflammatory mechanisms triggers insulin resistance and enhances the progression of atherosclerosis. Discovered first as an esterase that hydrolyze organophosphates, human paraoxonase-1 is bound to high-density lipoprotein and inhibits the oxidation of lipoproteins and reduces the degree of inflammation, hence it is considered to act against atherosclerosis. In contrast, the majority of the adipokines secreted from the enlarged white adipose tissue promote the atherosclerotic process; and altered adipokine secretion is now regarded as one of the major contributors of increased cardiovascular morbidity and mortality in obesity. In this review, we detail the correlations between paraoxonase-1 and some selected adipokines, namely leptin, adiponectin and chemerin. Adipokine imbalance leads to decreased paraoxonase-1 activity that results in enhanced atherosclerosis; therefore, altered adipokine secretion may be predictive of cardiovascular complications in obesity. As an active organ secreting biological active substances, white adipose tissue may also act as a "fine-tuner" of immune and endocrine actions attenuating or enhancing reactions triggered by pathogens, inflammation and metabolic stimuli; and obesity, as a chronic noxious state may perturb the proper functioning of this fine-tuning process. Further investigations are of major importance to elucidate the associations between adipokines and paraoxonase-1 and to establish accurate interventions against obesity-related disorders.
ESTHER : Fulop_2016_Chem.Biol.Interact_259_388
PubMedSearch : Fulop_2016_Chem.Biol.Interact_259_388
PubMedID: 27062889

Title : Relationship between serum paraoxonase and homocysteine thiolactonase activity, adipokines, and asymmetric dimethyl arginine concentrations in renal transplant patients - Locsey_2013_Transplant.Proc_45_3685
Author(s) : Locsey L , Seres I , Sztanek F , Harangi M , Padra J , Kovacs D , Fedor R , Asztalos L , Paragh G
Ref : Transplant Proc , 45 :3685 , 2013
Abstract : Paraoxonase lactonase activity protects against homocysteinylation; therefore, it can be a potential contributing factor to prevent atherosclerosis. We aimed to determine paraoxonase and HTLase activities and to clarify the relationship between HTLase activity and some cardiovascular risk factors, such as homocysteine, cystatin C asymmetric dimethylarginine (ADMA), and adipokines both in hemo dialyzed and transplanted patients. Among 114 hemodialyzed, 80 transplanted and 64 healthy control subjects, we investigated body mass index (BMI) as well as fasting serum contents of urea, uric acid, creatinine, cystatin C, homocysteine, glucose, lipids, total protein and albumin. Serum paraoxonase (PON 1) and HTLase activities were measured spectrophotometrically. ADMA, ADPN adiponectin, leptin (LEP) levels was determined with a sandwich enzyme-linked immunosorbent assay method. Dyslipidemic patients showed hypercholesterolemia, and high low-density lipoprotein (LDL); parallel with improved renal function, they displayed decreased cystatin C and homocysteine levels (P < .001). There was a significant negative correlation between PON 1 activity and cystatin C and homocysteine concentrations (P < .05). Obese patients revealed significantly higher LDL (P < .05) and leptin concentrations (P < .01). There was a significant positive correlation between PON 1 activity and adiponectin levels (P = .0276). Both dialyzed and transplanted patients displayed significantly lower HTLase activities compared to the control group (P < .001), particularly lower HTLase and PON 1 activities in dialyzed subjects compared with the transplanted group (P < .05). HTLase activity showed significant negative correlations with ADMA levels among the whole study population (P < .001), whereas positive associations were noted between PON 1 and HTLase activities (P < .001). HTLase activity may be a new predictor of cardiovascular risk in renal failure although it is modulated by other risk factors.
ESTHER : Locsey_2013_Transplant.Proc_45_3685
PubMedSearch : Locsey_2013_Transplant.Proc_45_3685
PubMedID: 24314997

Title : Effect of nutritional status on human paraoxonase-1 activity in patients with chronic kidney disease - Sztanek_2012_Kidney.Blood.Press.Res_36_310
Author(s) : Sztanek F , Seres I , Harangi M , Locsey L , Koncsos P , Paragh G
Ref : Kidney Blood Press Res , 36 :310 , 2012
Abstract : BACKGROUND/METHODS: The association between nutritional status, antioxidant human paraoxonase-1 (PON1) activity and low grade inflammation in hemodialized (HD) patients with chronic kidney disease (CKD) is unclear. The aim of this study was to determine PON1 paraoxonase and lactonase activities, ADMA, adiponectin and leptin concentrations, and to clarify the relationship between paraoxonase activity and a set of cardiovascular risk factors in malnourished, normal weight and obese HD patients; 114 HD patients with end-stage renal failure were enrolled.
RESULTS: Leptin levels were significantly higher and PON1 paraoxonase activities were significantly lower in obese patients compared to the other groups. Plasma adiponectin concentration was significantly lower in obese subjects compared to malnourished patients. Paraoxonase activity was negatively correlated with CRP level in HD and malnourished patients. Furthermore, we found significant inverse correlation between paraoxonase activity and BMI in the whole patient group. In multiple regression analysis, PON1 lactonase activity, CRP level and leptin concentration proved to be independent predictors of paraoxonase activity. CONCLUSION: Despite the previous findings of reverse epidemiology for the mortality rate of HD patients, further studies are needed to clarify the effects of nutritional state on atherosclerosis in obese and malnourished patients with end-stage renal failure.
ESTHER : Sztanek_2012_Kidney.Blood.Press.Res_36_310
PubMedSearch : Sztanek_2012_Kidney.Blood.Press.Res_36_310
PubMedID: 23235285

Title : Decreased paraoxonase 1 (PON1) lactonase activity in hemodialyzed and renal transplanted patients. A novel cardiovascular biomarker in end-stage renal disease - Sztanek_2012_Nephrol.Dial.Transplant_27_2866
Author(s) : Sztanek F , Seres I , Harangi M , Locsey L , Padra J , Paragh GJ , Asztalos L , Paragh G
Ref : Nephrol Dial Transplant , 27 :2866 , 2012
Abstract : BACKGROUND: Human paraoxonase-1 (PON1) has also been described as a lactonase. Decreased PON1 lactonase activity was found to be a predictor of cardiovascular disease. Homocysteine thiolactonase activity may prevent proteins from homocysteinylation and is thought to be a protective factor against the progression of atherosclerosis. Previous studies have demonstrated decreased PON1 paraoxonase activity in hemodialyzed (HD) and renal transplant (TRX) patients; however, lactonase activity has not been investigated. We aimed to determine the paraoxonase and lactonase activities and to clarify the relationship between lactonase activity and a set of cardiovascular risk factors, such as homocysteine, cystatin C and asymmetric dimethylarginine (ADMA) levels, in HD and TRX patients and in healthy controls.
METHODS: One hundred and eight HD and 78 TRX patients and 63 healthy controls were involved in the study. Paraoxonase and lactonase activities (paraoxon and gamma-thiobutyrolactone as substrates) were measured spectrophotometrically. ADMA level was determined with sandwich enzyme-linked immunosorbent assay.
RESULTS: Both HD and TRX patients had significantly lower lactonase activities compared to the control group (P<0.05). Significantly lower paraoxonase activities were found in HD patients compared to the TRX group (P<0.05). Significant negative correlation was found between lactonase activity and ADMA level in the whole study population (P<0.001), while paraoxonase and lactonase activities showed significant positive correlation (P<0.001). Multiple regression analysis identified paraoxonase activity and homocysteine level as independent predictors of lactonase activity. CONCLUSION: Lactonase activity is a potential new predictor of cardiovascular risk in renal failure. Measurement of lactonase activity is recommended in future studies on HD and TRX patients.
ESTHER : Sztanek_2012_Nephrol.Dial.Transplant_27_2866
PubMedSearch : Sztanek_2012_Nephrol.Dial.Transplant_27_2866
PubMedID: 22247228

Title : Low high-density lipoprotein cholesterol is not responsible for decreased paraoxonase activity in chronic renal failure - Varga_2012_Kidney.Blood.Press.Res_35_265
Author(s) : Varga E , Seres I , Harangi M , Karpati I , Koncsos P , Sztanek F , Paragh G
Ref : Kidney Blood Press Res , 35 :265 , 2012
Abstract : BACKGROUND/AIMS: Human paraoxonase-1 (PON1) is responsible for the antioxidant effect of high-density lipoprotein (HDL) by inhibiting low-density lipoprotein oxidation. Previous studies discovered dyslipidemia (DL) and decreased PON1 activity in chronic renal failure (CRF). We aimed to determine PON and arylesterase activity, phenotypic distribution of the PON1 enzyme, and lipid profile in low and normal HDL cholesterol (HDL-C) patients with CRF, and renal transplant (TX), compared to primary DL.
METHODS: 116 CRF (low or normal HDL-C), 52 TX (low or normal HDL-C), and 62 DL patients (low or normal HDL-C) were included. PON and arylesterase activities were measured spectrophotometrically. Phenotype was determined using the dual substrate method.
RESULTS: Aryl/HDL-C was significantly higher in low HDL-C patients. Patients with CRF had significantly lower arylesterase activity compared to DL, independent of HDL-C. PON activity and PON/HDL-C did not differ significantly in CRF compared to TX and DL. Phenotypic distribution was similar in patient groups. Low HDL-C CRF patients had significantly lower cholesterol and triglyceride than DL. CONCLUSION: Decreased arylesterase activity, correlating with PON1 enzyme protein quantity, is not explicable by decreased HDL-C in CRF. Low HDL-C CRF patients' increased cardiovascular morbidity is not attributable to changes in PON1 activity, or phenotypic distribution.
ESTHER : Varga_2012_Kidney.Blood.Press.Res_35_265
PubMedSearch : Varga_2012_Kidney.Blood.Press.Res_35_265
PubMedID: 22378349

Title : Favorable effect of short-term lifestyle intervention on human paraoxonase-1 activity and adipokine levels in childhood obesity - Koncsos_2011_J.Am.Coll.Nutr_30_333
Author(s) : Koncsos P , Seres I , Harangi M , Pall D , Jozsa L , Bajnok L , Nagy EV , Paragh G
Ref : J Am Coll Nutr , 30 :333 , 2011
Abstract : OBJECTIVE: The prevalence of obesity is increasing in adult and child populations throughout the world. Childhood obesity has a great impact on adult cardiovascular morbidity and mortality; treatment of this pathological state is important given the significant health consequences. We investigated the effect of short-term lifestyle changes on the alteration of human serum paraoxonase-1 (PON1) activities, leptin, adiponectin, E-selectin, and asymmetric dimethylarginine (ADMA) as atherogenic and antiatherogenic factors in obese children. PON1 protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low density lipoprotein (LDL) and therefore may protect against atherosclerosis.
METHODS: A total of 23 white obese and overweight children (age, 11.43 +/- 1.78 years; 8 girls, 15 boys) participated in a 2-week-long lifestyle camp based on a diet and exercise program. Overweight and obesity were defined according to the national body mass index (BMI) reference tables for age and sex.
RESULTS: After a 2-week-long supervised diet and aerobic exercise program, obese children had significantly lower leptin (55.02 +/- 33.42 ng/ml vs 25.37 +/- 19.07 ng/ml; p < 0.0001), ADMA (0.68 +/- 0.15 mumol/l vs 0.55 +/- 0.16 mumol/l; p < 0.01), and E-selectin levels (67.19 +/- 30.35 ng/ml vs 46.51 +/- 18.40 ng/ml; p < 0.0001), whereas they had significantly higher PON1 paraoxonase activity (110.48 +/- 72.92 U/l vs 121.75 +/- 93.48 U/l; p < 0.05) besides the antiatherogenic alteration of the lipid profile and significant weight change (70.32 +/- 19.51 kg vs 67.01 +/- 18.75 kg, p < 0.0001; BMI, 28.95 +/- 5.05 kg/m(2) vs 27.43 +/- 4.82 kg/m(2), p < 0.0001). Adiponectin and PON1 arylesterase activity did not change significantly.
CONCLUSIONS: Our investigation suggests that modifications in dietary habits and physical activity induce antiatherogenic changes in childhood obesity. These findings emphasize the major role of primary prevention and nonpharmaceutical treatment of childhood obesity through lifestyle changes based on diet and increased physical activity.
ESTHER : Koncsos_2011_J.Am.Coll.Nutr_30_333
PubMedSearch : Koncsos_2011_J.Am.Coll.Nutr_30_333
PubMedID: 22081619

Title : Paraoxonase-1 and clopidogrel efficacy -
Author(s) : Camps J , Joven J , Mackness B , Mackness MI , Tawfik DS , Draganov DI , Costa LG , Paragh G , Seres I , Horke S , James RW , Hernandez AF , Reddy ST , Shih DM , Navab M , Rochu D , Aviram M
Ref : Nat Med , 17 :1041 , 2011
PubMedID: 21900915

Title : Alteration of PON1 activity in adult and childhood obesity and its relation to adipokine levels - Seres_2010_Adv.Exp.Med.Biol_660_129
Author(s) : Seres I , Bajnok L , Harangi M , Sztanek F , Koncsos P , Paragh G
Ref : Advances in Experimental Medicine & Biology , 660 :129 , 2010
Abstract : Obesity as a pathogenic disorder is a predisposing factor for cardiovascular diseases and shows an increasing incidence in the industrialized countries. Adipokines such as leptin, adiponectin and resistin have a great impact on the development of atherosclerosis in obesity. Elevated levels of leptin have been found to be atherogenic whereas decreased levels of adiponectin have been proved to be anti-atherogenic in recent studies. The exact role of resistin in the process of atherosclerosis has so far remained uncertain and controversial. In our recent work, we studied the alteration in human paraoxonase-1 (PON1) activity and adipokine levels; furthermore, we also aimed at identifying the potential correlation between these parameters in this metabolic disorder. We investigated the above-mentioned parameters both in adults and in children, with regard to the emerging role of childhood obesity and to get a clearer view of these factors during a whole lifetime. Investigating the adult population with a broad range of body mass index (BMI) we found significantly increased leptin and significantly decreased adiponectin and resistin levels and PON1 activity in the obese group compared to the lean controls. Adiponectin and resistin levels showed significantly positive correlation, while leptin and BMI showed significantly negative correlation with PON1 activity. Our findings were similar in childhood obesity: leptin showed significantly negative correlation, while adiponectin showed significantly positive correlation with PON1 activity. We found gender differences in the univariate correlations of leptin and adiponectin levels with PON1 activity in the adult population. In multiple regression analysis, adiponectin proved to be an independent factor of PON1 activity both in childhood and adult obesity, furthermore thiobarbituric acid-reactive substances (TBARS) also proved to be an independent predictor of the enzyme in adults, reflecting the important role of oxidative stress in obesity. Investigating PON 192 Q/R polymorphism by phenotypic distribution (A/B isoenzyme) in obese children, we found a significant correlation of PON1 arylesterase activity with leptin and adiponectin levels, and of body fat percentage with PON1 192 B isoenzyme. According to our studies, these metabolic changes in obesity predispose to the early development of atherosclerosis throughout our whole lifetime. Decreased activity of PON1 and alterations in adipokine levels in childhood obesity could contribute to an early commencement of this process, detected only later in adulthood by increased cardiovascular morbidity and mortality. Changed levels of leptin, adiponectin, resistin and PON1 activity at all ages, just like 192 Q/R polymorphism determined by phenotypic distribution, may be useful markers beside the general risk factors.
ESTHER : Seres_2010_Adv.Exp.Med.Biol_660_129
PubMedSearch : Seres_2010_Adv.Exp.Med.Biol_660_129
PubMedID: 20221876

Title : Decreased human paraoxonase-1 activity in patients with Sjogren's syndrome - Szanto_2010_Int.Immunol_22_605
Author(s) : Szanto A , Harangi M , Seres I , Paragh G , Zeher M
Ref : Int Immunol , 22 :605 , 2010
Abstract : OBJECTIVES: The aim of the study was to examine human serum paraoxonase 1 (PON1) activity, phenotype distribution and lipid parameters in patients with Sjogren's syndrome. The prevalence of cardio- and cerebrovascular diseases in SS patients was also evaluated after a 5-year follow-up.
METHODS: Fifty-seven SS patients and 17 age-matched healthy controls were enrolled into the study. PON1 and arylesterase activities were measured spectrophotometrically. The phenotype distribution of PON1 was determined by the dual-substrate method.
RESULTS: Significantly lower PON1 activity was found in patients with SS compared with the control group (98.00 +/- 69.21 versus 203.3 +/- 92.78 U ml(-1); P < 0.001). There were significant differences in PON1 phenotype distribution of SS patients and controls (AA/AB/BB: 91.2/8.8/0 versus 58.8/29.4/11.8%; P < 0.01). No significant correlations were found between PON activity and disease-characteristic autoantibodies, including anti-Ro/SS-A and anti-La/SS-B concentrations. PON activity did not predict the cerebro/cardiovascular risk in SS patients during the 5-year follow-up.
CONCLUSIONS: Despite the relatively small sample size that reduces the power of the study, decreased PON activity may be a possible cardiovascular risk factor in SS. Disadvantageous PON1 phenotype distribution may contribute to the decreased PON activity in these patients.
ESTHER : Szanto_2010_Int.Immunol_22_605
PubMedSearch : Szanto_2010_Int.Immunol_22_605
PubMedID: 20497955

Title : Human paraoxonase-1 activity in childhood obesity and its relation to leptin and adiponectin levels - Koncsos_2010_Pediatr.Res_67_309
Author(s) : Koncsos P , Seres I , Harangi M , Illyes I , Jozsa L , Gonczi F , Bajnok L , Paragh G
Ref : Pediatr Res , 67 :309 , 2010
Abstract : Childhood obesity is a predisposing factor for adult cardiovascular diseases. Human serum paraoxonase (PON1) may protect against atherosclerosis by hydrolyzing lipid peroxides in oxidized LDL. Alterations and potential correlations of PON1 activities, leptin and adiponectin levels in childhood obesity were studied. We measured PON1 paraoxonase and arylesterase activities, anthropometric parameters, leptin and adiponectin levels in 59 white, obese (obese group-OB: BMI corrected for age: 95.1 +/- 3.5 percentile, age: 11.9 +/- 1.6 y) and 51 normal-weight children (control group-C: BMI corrected for age: 64.1 +/- 8.4 percentile, age: 12.0 +/- 3.9 y). Obese children had significantly lower PON1 paraoxonase (OB: 84.80 (64.33/144.74) U/L versus. C: 99.42 (83.33/152.05) U/L; p < 0.05) and arylesterase activities (OB: 94.40 (82.20/108.70) U/L versus. C: 115.20 (93.70/126.00) U/L; p < 0.01), higher leptin (OB: 37.05 (24.33/53.87) ng/mL versus. C: 4.62 (2.52/17.6) ng/mL; p < 0.0001) and lower adiponectin levels (OB: 7.56 (5.69/12.06) microg/mL versus. C: 11.51 (8.84/14.49) microg/mL; p < 0.001) compared with the normal-weight group. PON1 arylesterase activity showed inverse univariate correlation with leptin (r = -0.29; p < 0.05) and positive correlation with adiponectin levels (r = 0.39; p < 0.01). In multiple regression analysis adiponectin was strongly associated with PON1 arylesterase activity in obese children (beta = 0.45, p < 0.02). Our results emphasize the importance of the investigated metabolic alterations which may have further effects on cardiovascular morbidity and mortality in later adulthood. Altered levels of leptin, adiponectin and PON1 activities may be useful markers beside the general risk factors in childhood obesity.
ESTHER : Koncsos_2010_Pediatr.Res_67_309
PubMedSearch : Koncsos_2010_Pediatr.Res_67_309
PubMedID: 19915520

Title : Discordance in human paraoxonase-1 gene between phenotypes and genotypes in chronic kidney disease - Paragh_2009_Nephron.Clin.Pract_113_c46
Author(s) : Paragh G , Seres I , Harangi M , Pocsai Z , Asztalos L , Locsey L , Szeles G , Kardos L , Varga E , Karpati I , Adany R
Ref : Nephron Clin Pract , 113 :c46 , 2009
Abstract : BACKGROUND: Human serum paraoxonase-1 (PON1) is a high-density lipoprotein-associated ester hydrolase which can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Two common polymorphisms are known in the PON1 gene in humans (at positions 55 and 192), from which the latter gene alteration has been mainly attributed to alter the activity of the protein. Moreover, significantly reduced PON1 activity was found in chronic kidney disease (CKD) and renal transplant patients.
METHODS: The aim of the present study was to investigate the genotype and phenotype distribution of the PON1 gene as well as its end product activity in patients with CKD (n = 117), in renal transplant recipients (n = 146) and in reference subjects (n = 1,180).
RESULTS: Unexpectedly high discordances between phenotype and genotype assessments were observed in all studied groups (28.2% in the CKD, 20.55% in the transplant and 30.9% in the reference group). Arylesterase activity was significantly lower in the CKD group compared to the reference sample. There were no significant differences between patients and the reference group in the frequencies of polymorphisms PON1-55 and PON1-192. PON1 activity did not differ in patients compared to the reference group.
CONCLUSIONS: Both PON1 phenotype and genotype determinations are necessary to estimate PON1 status.
ESTHER : Paragh_2009_Nephron.Clin.Pract_113_c46
PubMedSearch : Paragh_2009_Nephron.Clin.Pract_113_c46
PubMedID: 19602899

Title : Associations of adiponectin with paraoxonase 1 and sE-selectin in hemodialyzed patients - Peti_2009_Kidney.Blood.Press.Res_32_360
Author(s) : Peti A , Csiky B , Guth E , Kenyeres P , Varga Z , Seres I , Jeney Z , Juhasz M , Mezosi E , Paragh G , Kovacs GL , Bajnok L
Ref : Kidney Blood Press Res , 32 :360 , 2009
Abstract : BACKGROUND/AIMS: In hemodialyzed (HD) patients, adiponectin and sE-selectin levels are elevated, while antioxidant paraoxonase 1 activity (PON1) is decreased. We determined if the hyperadiponectinemia in HD patients has a protective effect on the decrease in PON1 and elevation in sE-selectin in kidney failure. METHODS and Design: Predialysis serum adiponectin, PON1 and sE-selectin as well as other metabolic variables were measured in 70 HD patients.
RESULTS: Adiponectin had (1) no association with PON1 or sE-selectin, (2) a positive association with dialysis efficiency and HDL-C, and (3) an inverse association with BMI, waist circumference, HOMA IR, triglyceride, hsCRP, fibrinogen, and albumin. Moreover, albumin, BMI, and HOMA-IR were independent negative predictors of adiponectin.
CONCLUSIONS: In kidney failure, in contrast to normal renal function, higher adiponectin levels had no correlation with PON1 activity or the sE-selectin level. However, adiponectin has an association with dialysis efficiency and, similar to individuals with preserved kidney function, traits of metabolic syndrome. In addition to BMI and HOMA-IR, the serum albumin concentration is also one of the independent negative predictors of the serum adiponectin level. Collectively, these findings may add details to the understanding of the role that adiponectin plays in chronic renal disease related to 'reverse epidemiology'.
ESTHER : Peti_2009_Kidney.Blood.Press.Res_32_360
PubMedSearch : Peti_2009_Kidney.Blood.Press.Res_32_360
PubMedID: 19887823

Title : Acute hypertriglyceridemic pancreatitis during pregnancy due to homozygous lipoprotein lipase gene mutation -
Author(s) : Bartha I , Dinya T , Seres I , Paragh G , Ross C , Hayden MR , Biro S , Vargha G
Ref : Clinica Chimica Acta , 400 :137 , 2009
PubMedID: 19000906

Title : Serum cystatin C is a determinant of paraoxonase activity in hemodialyzed and renal transplanted patients - Varga_2009_Dis.Markers_26_141
Author(s) : Varga E , Seres I , Harangi M , Sztanek F , Asztalos L , Locsey L , Borbas B , Szegedi J , Karpati I , Paragh G
Ref : Dis Markers , 26 :141 , 2009
Abstract : BACKGROUND: Human paraoxonase-1 (PON1) inhibits LDL-oxidation and atherogenesis, and possesses lactonase activity. Decreased PON1 activity was found in hemodialyzed and renal transplanted patients. Cystatin C plays a protective role in atherosclerosis, and is a new, sensitive marker of renal function. The relationship between these two markers in renal failure has not been investigated. AIMS: The goal of this study was to clarify the relationship between PON1 activity, cystatin C and homocysteine in chronic renal failure. We also determined the levels of oxidatively modified LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) to characterize lipid peroxidation. PATIENTS AND
METHODS: 74 hemodialized (HD), 171 renal transplanted patients (TRX), and 110 healthy controls (C) were involved in the study. PON1 activity and TBARS levels were measured spectrophotometrically. OxLDL level was determined with sandwich ELISA.
RESULTS: There was a negative correlation between PON1 activity and cystatin C level. Homocysteine level correlated negatively with PON1 activity, and positively with cystatin C level. OxLDL and TBARS levels were significantly higher in the HD and TRX groups compared to C.
CONCLUSIONS: Cystatin C may be a good predictive factor not only for homocysteine levels but for the antioxidant status in patients with renal failure and renal transplantation.
ESTHER : Varga_2009_Dis.Markers_26_141
PubMedSearch : Varga_2009_Dis.Markers_26_141
PubMedID: 19597297

Title : Atorvastatin effect on the distribution of high-density lipoprotein subfractions and human paraoxonase activity - Harangi_2009_Transl.Res_153_190
Author(s) : Harangi M , Mirdamadi HZ , Seres I , Sztanek F , Molnar M , Kassai A , Derdak Z , Illyes L , Paragh G
Ref : Transl Res , 153 :190 , 2009
Abstract : Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (LDL); therefore, it may protect against atherosclerosis. Changes in the ratio of high-density lipoprotein (HDL) subfractions may alter the stability and the antioxidant capacity of PON1. The aim of the study was to examine the effect of atorvastatin treatment on the distribution of HDL subfractions, LDL size, cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and PON1 activity. In all, 33 patients with type IIa and IIb hypercholesterolemia were involved in the study. LDL sizes and HDL subfractions were determined by gradient gel electrophoresis. CETP, LCAT, and PON1 activities were measured spectrophotometrically. Three months of treatment with atorvastatin 20 mg daily significantly increased the HDL3 (+8.13%) and decreased the HDL2a and HDL2b subfractions (-1.57% and -6.55%, respectively). The mean LDL size was significantly increased (+3.29%). The level of oxidized LDL was significantly decreased (-46.0%). The PON1 activity was augmented by the atorvastatin treatment (+5.0%). The CETP activity positively correlated with the HDL2b level and negatively correlated with the HDL3 and HDL2a levels. Atorvastatin alters the HDL subfractions, which may improve its antiatherogenic effect via enhancement of the PON1 activity.
ESTHER : Harangi_2009_Transl.Res_153_190
PubMedSearch : Harangi_2009_Transl.Res_153_190
PubMedID: 19304278

Title : Benefits and difficulties in measuring HDL subfractions and human paraoxonase-1 activity during statin treatment - Harangi_2009_Cardiovasc.Drugs.Ther_23_501
Author(s) : Harangi M , Seres I , Harangi J , Paragh G
Ref : Cardiovasc Drugs Ther , 23 :501 , 2009
Abstract : Dyslipidaemia including decreased high density lipoprotein cholesterol concentration is one of several factors that have been implicated in increased cardiovascular risk. Since their introduction in the 1980s, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have emerged as the one of the best-selling class of medications to date, with numerous trials demonstrating powerful efficacy in preventing cardiovascular diseases. Although statins have been shown to modestly raise or not alter HDL-cholesterol, their effect on HDL subfractions and on HDL-associated enzymes including human paraoxonase-1 (PON1) has not yet been fully explored. This review summarizes the currently available data on the effect of statins on HDL subfractions and on PON1 activity with a particular emphasis on the clinical relevance of these effects. Moreover, methodological problems of HDL subfraction and PON1 activity determinations are also discussed.
ESTHER : Harangi_2009_Cardiovasc.Drugs.Ther_23_501
PubMedSearch : Harangi_2009_Cardiovasc.Drugs.Ther_23_501
PubMedID: 19859794

Title : The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters - Mirdamadi_2008_Br.J.Clin.Pharmacol_66_366
Author(s) : Mirdamadi HZ , Sztanek F , Derdak Z , Seres I , Harangi M , Paragh G
Ref : British Journal of Clinical Pharmacology , 66 :366 , 2008
Abstract : AIMS: Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters.
METHODS: One hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day(-1) atorvastatin, 10/20 mg day(-1) simvastatin and 80 mg day(-1) extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method.
RESULTS: Three months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group.
CONCLUSIONS: The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.
ESTHER : Mirdamadi_2008_Br.J.Clin.Pharmacol_66_366
PubMedSearch : Mirdamadi_2008_Br.J.Clin.Pharmacol_66_366
PubMedID: 18492126

Title : Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity - Kerekes_2008_J.Rheumatol_35_398
Author(s) : Kerekes G , Szekanecz Z , Der H , Sandor Z , Lakos G , Muszbek L , Csipo I , Sipka S , Seres I , Paragh G , Kappelmayer J , Szomjak E , Veres K , Szegedi G , Shoenfeld Y , Soltesz P
Ref : J Rheumatol , 35 :398 , 2008
Abstract : OBJECTIVE: Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. We assessed endothelial dysfunction and atherosclerosis in RA in context with laboratory markers.
METHODS: Fifty-two patients with RA and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT) and flow- (FMD) and nitroglycerine-mediated vasodilation (NMD). We also assayed numerous immunological and metabolic laboratory markers.
RESULTS: FMD was significantly lower in RA (5.32% +/- 4.66%) compared to controls (8.30% +/- 3.96%) (p = 0.001). NMD was preserved in RA. ccIMT was significantly greater in patients with RA (0.63 +/- 0.14 mm) versus controls (0.54 +/- 0.15 mm) (p = 0.012). In patients with RA, ccIMT correlated with FMD% (R = -0.318, p = 0.022), age (R = 0.831, p < 0.001), and anti-dsDNA levels (R = 0.463, p = 0.006). FMD% correlated with serum interferon-gamma (IFN-gamma) levels (R = 0.516, p = 0.014). NMD% correlated inversely with the percentage of Th0 lymphocytes (R = -0.636, p = 0.006), serum immune complex (R = -0.692, p < 0.001), and IgM levels (R = -0.606, p = 0.003). Patients with RA were divided as "low" (< 0.65 mm) versus "high" (> 0.65 mm) ccIMT groups, and into "normal" (> 5%) versus "impaired" (< 5%) FMD% subsets. Low and high ccIMT groups differed significantly in age and serum interleukin 1 (IL-1) and anti-dsDNA levels. RA patients with normal versus impaired FMD% differed significantly in age, disease duration, and serum IFN-gamma levels. Lipoprotein(a) [Lp(a)] also correlated with rheumatoid factor (RF) and C-reactive protein (CRP); homocysteine (HCy) correlated with CRP and correlated inversely with folate and vitamin B12 production. Paraoxonase-1 (PON-1) activity correlated with serum tumor necrosis factor-alpha(TNF-alpha) and IL-6 levels. CONCLUSION: This was a well characterized RA population, where FMD and ccIMT were impaired, indicating early endothelial dysfunction and accelerated atherosclerosis, respectively. RA-related autoimmune-inflammatory mechanisms and metabolic factors including anti-CCP, RF, CRP, circulating immune complexes, IgM, TNF-alpha, IL-6, Th0/Th1 ratio, HCy, folate, vitamin B12, and PON-1 may all be involved in the development of vascular disease in RA. Although ccIMT and FMD, as well as some laboratory factors, have been assessed by other investigators in RA-associated atherosclerosis, our results regarding the possible involvement of anti-CCP, anti-dsDNA, Lp(a), some cytokines, and PON-1 activity are novel. Early determination of FMD% and ccIMT may be useful to assess RA patients with high cardiovascular risk.
ESTHER : Kerekes_2008_J.Rheumatol_35_398
PubMedSearch : Kerekes_2008_J.Rheumatol_35_398
PubMedID: 18203326

Title : Relationship of adiponectin to serum paraoxonase 1 - Bajnok_2008_Atherosclerosis_197_363
Author(s) : Bajnok L , Csongradi E , Seres I , Varga Z , Jeges S , Peti A , Karanyi Z , Juhasz A , Mezosi E , Nagy EV , Paragh G
Ref : Atherosclerosis , 197 :363 , 2008
Abstract : Correlation of the plasma levels of insulin-sensitizing, anti-inflammatory and anti-atherosclerotic adiponectin with HDL has been demonstrated. However, its relation to HDL-bound paraoxonase 1 (PON1) has not been clarified. The association of serum PON1 activity with findings of metabolic syndrome was investigated in three age and sex-matched groups: (1) non-diabetic overweight subjects with BMI 28-39.9 kg/m(2) (n=25); (2) non-diabetic obese subjects with BMI>or=40 kg/m(2) (n=25); and (3) healthy, normal-weight controls (n=24). Of the parameters investigated, PON1 activity correlated positively with concentrations of HDL-C and adiponectin, and correlated negatively with BMI, waist circumference, systolic BP, levels of HbA(1C), and insulin, HOMA-IR, and TBARS. The positive correlation between adiponectin and PON1 remained significant even after adjustments for age, gender, BMI, blood pressure, HOMA-IR, HDL-C, LDL-C, and lipid peroxidation.
CONCLUSIONS: PON1 activity shows negative association with markers of metabolic syndrome. We demonstrate that adiponectin is an independent variable of serum PON1, which may contribute to the anti-atherosclerotic effect of adiponectin.
ESTHER : Bajnok_2008_Atherosclerosis_197_363
PubMedSearch : Bajnok_2008_Atherosclerosis_197_363
PubMedID: 17624354

Title : Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index - Bajnok_2008_Exp.Clin.Endocrinol.Diabetes_116_592
Author(s) : Bajnok L , Seres I , Varga Z , Jeges S , Peti A , Karanyi Z , Juhasz A , Csongradi E , Mezosi E , Nagy EV , Paragh G
Ref : Experimental & Clinical Endocrinology & Diabetes Diabetes , 116 :592 , 2008
Abstract : The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, P<0.05), waist circumference (r=-0.28, P<0.05), serum levels of leptin (r=-0.28, P<0.05), non-esterified fatty acids (NEFA) (r=-0.23, P<0.05), and HbA (1C) (r=-0.26, P<0.05), systolic BP (r=-0.28, P<0.05), and lipid peroxidation (measured by TBARS) (r=-0.40, P<0.01), and correlated positively with PON1 (r=0.24, P<0.05). No association was detected between the serum concentrations of resistin and the following investigated parameters: diastolic BP, levels of uric acid, glucose, insulin, or insulin resistance (measured by homeostasis model assessment, HOMA-IR), triglyceride, total cholesterol, LDL-C, and HDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not.
CONCLUSIONS: Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.
ESTHER : Bajnok_2008_Exp.Clin.Endocrinol.Diabetes_116_592
PubMedSearch : Bajnok_2008_Exp.Clin.Endocrinol.Diabetes_116_592
PubMedID: 18465683

Title : Association between human paraoxonase 1 activity and intima-media thickness in subjects under 55 years of age with carotid artery disease - Harangi_2008_Cerebrovasc.Dis_25_122
Author(s) : Harangi M , Seres I , Magyar MT , Csipo I , Sipka S , Valikovics A , Csiba L , Bereczki D , Paragh G
Ref : Cerebrovasc Dis , 25 :122 , 2008
Abstract : BACKGROUND: Human serum paraoxonase (PON1) protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein (oxLDL); therefore, it may protect against atherosclerosis. PON1 activity and polymorphisms have been inconsistently associated with carotid artery disease. The goal of this study was to clarify the role of PON1 activity and phenotype on carotid artery disease and its correlation with some inflammatory and immune markers in subjects under 55 years with early-onset carotid atherosclerosis.
METHODS: Sixty patients with occlusive carotid artery disease and 30 healthy controls were enrolled. Intima-media thickness (IMT) was measured by high-resolution ultrasound of both common carotid arteries. Anti-oxLDL antibody levels were determined by ELISA.
RESULTS: In the whole study population we found a negative correlation between PON1 activity and IMT (r = -0.27, p = 0.011), and between salt-stimulated PON1 activity and IMT (r = -0.24, p = 0.02). Both PON1 activity and salt-stimulated PON1 activity negatively correlated with anti-oxLDL levels (r = -0.28, p = 0.008; r = -0.26, p = 0.01). PON1 activity was lower in patients compared to controls; however, the difference was not significant.PON1 phenotype distribution of patients and controls did not differ significantly. CONCLUSION: The importance of PON1 activity as a predictive risk factor for early-onset occlusive carotid artery disease should be assessed in future studies.
ESTHER : Harangi_2008_Cerebrovasc.Dis_25_122
PubMedSearch : Harangi_2008_Cerebrovasc.Dis_25_122
PubMedID: 18073465

Title : Evaluation of paraoxonase activity in patients with mixed connective tissue disease - Bodolay_2008_J.Rheumatol_35_237
Author(s) : Bodolay E , Seres I , Szodoray P , Csipo I , Jakab Z , Vegh J , Szilagyi A , Szegedi G , Paragh G
Ref : J Rheumatol , 35 :237 , 2008
Abstract : OBJECTIVE: Mixed connective tissue disease (MCTD) is a systemic inflammatory autoimmune disease. The connection between inflammatory measures and atherosclerosis in MCTD has not been described. Paraoxonase (PON) is known to have an antioxidant function. We evaluated lipid profiles and PON activity in patients with MCTD.
METHODS: Thirty-seven patients with MCTD were enrolled. Patients had taken no antihyperlipidemic drugs in the past 2 months. Thirty healthy individuals served as controls. The mean age of patients was 51.2 +/- 9.5 years; disease duration was 11.0 +/- 7.2 years. PON activity was determined with spectrophotometry, von Willebrand factor (vWF) antigen was investigated with the immunoturbidimetry method, and thrombomodulin and antiendothelial cell antibody (AECA) measurements were carried out by ELISA.
RESULTS: PON activity in patients with MCTD was significantly lower than in the controls (patients 118.5 +/- 64.6 U/l, controls 188.0 +/- 77.6; p < 0.001). Arylesterase activity was significantly reduced in patients (p < 0.001). Reduction of PON activity showed a close correlation with the age of the patients, duration of the disease, and vascular events (eye, cardiac, cerebral). There was a close association between the low PON activity and endothelial cell activation markers (thrombomodulin, vWF, AECA). CONCLUSION: Our results indicate that in patients with MCTD there is an increased risk for atherosclerosis. In the development of atherosclerosis, besides the elevated levels of cholesterol and triglyceride, reduced PON concentrations and PON activity may play a crucial role.
ESTHER : Bodolay_2008_J.Rheumatol_35_237
PubMedSearch : Bodolay_2008_J.Rheumatol_35_237
PubMedID: 18085736

Title : The effect of atorvastatin therapy on lecithin:cholesterol acyltransferase, cholesteryl ester transfer protein and the antioxidant paraoxonase - Kassai_2007_Clin.Biochem_40_1
Author(s) : Kassai A , Illyes L , Mirdamadi HZ , Seres I , Kalmar T , Audikovszky M , Paragh G
Ref : Clinical Biochemistry , 40 :1 , 2007
Abstract : OBJECTIVES: The aim of our study was to examine the influence of atorvastatin on lipid parameters, particularly on HDL, and on the activity of LCAT and CETP and how they affect the activity of the HDL-associated antioxidant enzyme paraoxonase. DESIGN AND
METHODS: Thirty-three patients with types II.a and II.b primary hyperlipoproteinemia were enrolled into our study. The patients received atorvastatin, 20 mg daily, for 3 months. We measured the serum paraoxonase activity and concentration, oxidized LDL, LCAT and CETP activities.
RESULTS: Atorvastatin significantly reduced the levels of cholesterol, triglyceride, LDL-C and apoB, while it did not influence the levels of HDL-C and apo A-I. The increases in serum PON-specific activity, PON/HDL ratio and LCAT activity were significant, while oxLDL and CETP activities were significantly decreased. CONCLUSION: Atorvastatin may influence the composition and function of HDL, thereby possibly increasing the activity of paraoxonase and preventing atherosclerosis.
ESTHER : Kassai_2007_Clin.Biochem_40_1
PubMedSearch : Kassai_2007_Clin.Biochem_40_1
PubMedID: 16999950

Title : Reduced paraoxonase1 activity is a risk for atherosclerosis in patients with systemic lupus erythematosus - Kiss_2007_Ann.N.Y.Acad.Sci_1108_83
Author(s) : Kiss E , Seres I , Tarr T , Kocsis Z , Szegedi G , Paragh G
Ref : Annals of the New York Academy of Sciences , 1108 :83 , 2007
Abstract : Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonasel (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDL-C, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.
ESTHER : Kiss_2007_Ann.N.Y.Acad.Sci_1108_83
PubMedSearch : Kiss_2007_Ann.N.Y.Acad.Sci_1108_83
PubMedID: 17893973

Title : Orlistat increases serum paraoxonase activity in obese patients - Audikovszky_2007_Nutr.Metab.Cardiovasc.Dis_17_268
Author(s) : Audikovszky M , Pados G , Seres I , Harangi M , Fulop P , Katona E , Illyes L , Winkler G , Katona EM , Paragh G
Ref : Nutr Metab Cardiovasc Dis , 17 :268 , 2007
Abstract : BACKGROUND AND AIM: Previous studies have demonstrated that oxidative stress is increased in obese patients. The high-density lipoprotein (HDL) associated human paraoxonase 1 (PON1) can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. Our objective was to assess the effects of orlistat therapy combined with diet on body mass index (BMI), waist circumference, lipid parameters, blood pressure, serum glucose level and PON1 activity. METHODS AND
RESULTS: A longitudinal, multicenter, randomized study with and without orlistat treatment was performed. One hundred thirty nine otherwise healthy, obese subjects were divided in to two groups: 78 persons received orlistat (120 mg three times a day) combined with diet while 61 persons were kept on diet only. Anthropometrical parameters, serum lipid levels and PON1 activity were measured at baseline and after 6 months of treatment. BMI and waist circumference were reduced more pronouncedly in the orlistat group than in the control group. Patients receiving orlistat also had significantly greater improvements in fasting blood glucose levels and blood pressure. The orlistat-treated group showed a greater reduction in total cholesterol and triglyceride levels. In addition, the serum PON1 activity in these patients was significantly increased compared to the diet-only group.
CONCLUSIONS: The 6-month treatment with orlistat had a beneficial effect on the lipid profile and improved the antioxidant status by increasing serum PON1 activity. However, because of the limited therapeutic effectiveness, obese patients with hypercholesterolemia should receive additional lipid lowering medications.
ESTHER : Audikovszky_2007_Nutr.Metab.Cardiovasc.Dis_17_268
PubMedSearch : Audikovszky_2007_Nutr.Metab.Cardiovasc.Dis_17_268
PubMedID: 17134960

Title : Relationship of endogenous hyperleptinemia to serum paraoxonase 1, cholesteryl ester transfer protein, and lecithin cholesterol acyltransferase in obese individuals - Bajnok_2007_Metabolism_56_1542
Author(s) : Bajnok L , Seres I , Varga Z , Jeges S , Peti A , Karanyi Z , Juhasz A , Csongradi E , Mezosi E , Nagy EV , Paragh G
Ref : Metabolism , 56 :1542 , 2007
Abstract : Altered activities of high-density lipoprotein (HDL)-associated antioxidant enzyme paraoxonase 1 (PON1) and lipid transfer proteins, for example, cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT), participating in lipoprotein remodeling seem to play important roles in obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum leptin levels have been demonstrated. However, the relationship of leptin with CETP and LCAT in humans is less clear. Our aims were to investigate whether the elevated leptin level is (a) an independent predictor of low PON1 and (b) associated with alterations of CETP and LCAT activities. Seventy-four white subjects forming 3 age- and sex-matched groups were included into the study (groups 1 and 2: nondiabetic obese patients, n = 25 with body mass index [BMI] 28-39.9 kg/m2 and n = 25 with BMI >or=40 kg/m2, respectively; and group 3: 24 healthy, normal-weight control subjects). Paraoxonase 1 correlated inversely with BMI (r = -0.39, P < .01), waist circumferences (r = -0.42, P < .001), and leptin concentrations (r = -0.38, P < .001). However, in a multiple regression model, neither these variables nor others, for example, age, sex, blood pressure, insulin resistance (in homeostasis model assessment of insulin resistance [HOMA-IR]), HDL cholesterol, low-density lipoprotein cholesterol, or lipid peroxidation (measured as thiobarbituric acid reactive substances), proved to be independent predictors of PON1. Lecithin cholesterol acyltransferase correlated negatively with BMI (r = -0.40, P < .01), waist circumferences (r = -0.42, P < .001), and leptin levels (r = -0.40, P < .01). During multiple regression analyses, BMI was an independent predictor of LCAT after adjustments for age, sex, HOMA-IR, and HDL cholesterol. However, this was replaced by leptin and HOMA-IR when leptin was also included into the model. The CETP activities correlated with HOMA-IR (r = 0.33, P < .01), thiobarbituric acid reactive substances (r = 0.45, P < .001), and leptin (r = 0.36, P < .01) levels in univariate but not in multivariate models. Elevated leptin level is an independent predictor of low LCAT, but not PON1, activity. In a population with a wide range of BMI, LCAT correlates inversely with obesity and CETP directly with insulin resistance.
ESTHER : Bajnok_2007_Metabolism_56_1542
PubMedSearch : Bajnok_2007_Metabolism_56_1542
PubMedID: 17950106

Title : Ciprofibrate increases paraoxonase activity in patients with metabolic syndrome - Paragh_2006_Br.J.Clin.Pharmacol_61_694
Author(s) : Paragh G , Seres I , Harangi M , Erdei A , Audikovszky M , Debreczeni L , Kovacsay A , Illyes L , Pados G
Ref : British Journal of Clinical Pharmacology , 61 :694 , 2006
Abstract : AIMS: Diabetic dyslipidaemia with decreased high-density lipoprotein-cholesterol (HDL-C) concentration plays a key role in enhanced atherosclerosis. The antioxidant effect of HDL is due to the influence of human paraoxonase 1 (PON1) and several authors have described decreased activity of this enzyme in Type 2 diabetics and subjects with metabolic syndrome. The goal of this study was to examine the effect of daily ciprofibrate on serum PON1 and lipoprotein concentrations in patients with metabolic syndrome.
METHODS: Fifty-one patients with metabolic syndrome were enrolled into the study. We examined the effect of 100 mg day(-1) ciprofibrate treatment on lipid concentrations, oxidized low-density lipoprotein (LDL), PON1 concentrations and activity. We also investigated the calculated size of LDL-cholesterol (LDL-C).
RESULTS: During the 3-month study, it was observed that following treatment with ciprofibrate, the serum triglyceride concentration decreased significantly (from 2.76 +/- 0.9 mmol l(-1) to 2.27 +/- 1.6 mmol l(-1); -18%; P < 0.001), while HDL-C increased significantly (from 0.95 +/- 0.2 mmol l(-1) to 1.2 +/- 0.3 mmol l(-1); 26%; P < 0.001). The oxidatively modified LDL-C concentration decreased significantly (from 137 +/- 19 U l(-1) to 117 +/- 20 U l(-1); P < 0.001), while HDL-associated apolipoprotein A1 significantly increased (from 1.35 +/- 0.2 g l(-1) to 1.75 +/- 0.3 g l(-1); P < 0.001). The LDL-C/LDL-apoB ratio, which reflects the size of LDL, increased significantly (from 0.96 +/- 0.05 to 1.05 +/- 0.06; P < 0.05). Serum PON1 activity was significantly elevated (from 108 +/- 34 U l(-1) to 129 +/- 31 U l(-1); P < 0.05), while standardized values for HDL-C remained significantly unchanged (PON1/HDL-C) (from 114 +/- 21 to 107 +/- 20; NS). CONCLUSION: Three months of treatment with ciprofibrate favourably affected the lipid profile, increased LDL resistance to oxidation and improved antioxidant status by increasing serum paraoxonase activity in these patients.
ESTHER : Paragh_2006_Br.J.Clin.Pharmacol_61_694
PubMedSearch : Paragh_2006_Br.J.Clin.Pharmacol_61_694
PubMedID: 16722831

Title : Paraoxonase gene polymorphism and serum activity in progressive IgA nephropathy - Kovacs_2006_J.Nephrol_19_732
Author(s) : Kovacs TJ , Harris S , Vas TK , Seres I , Short CD , Wittmann IK , Paragh G , Mackness MI , Mackness B , Durrington PN , Nagy JM , Brenchley PE
Ref : J Nephrol , 19 :732 , 2006
Abstract : BACKGROUND: HDL-associated paraoxonase (PON1) reduces oxidation of lipids in LDL, and activity is inversely related to coronary heart disease risk with a beneficial effect on the development of atherosclerosis. Risk factors associated with atherosclerosis, such as hypertension, dyslipidemia and smoking, also promote the progression of chronic glomerulonephritides which may therefore be associated with perturbations in PON1 activity.
METHODS: We performed a genetic association study in patients with IgA nephropathy (IgAN) (n=115) compared with control subjects (n=118). The aim was to test whether polymorphisms in the PON1 coding region (Q192R and L55M) and its promoter (-108C/T and -162A/G) are associated with either IgAN or with the progression. We measured serum paraoxonase activity in 60 out of 115 patients. All patients had been followed up for more than 4 years.
RESULTS: There were no differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M and -108C/T) between the patients and controls. However, the frequency distribution at -162 position (A/G) was significantly diffe-rent in IgAN (p=0.028, chi-square test) with a higher frequency of the heterozygote (0.017, Fisher exact test [FE]; odds ratio [OR] = 1.99; 95% confidence interval [95% CI], 1.14-3.47). Although there were no differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M and -162C/T) between the patients with progressive IgA and the nonprogressive patients, we found that the frequency of the C allele for the -108C/T polymorphism was elevated in those patients with nonprogressive disease (n=85) compared with those with progressive disease (n=30) (61% vs. 47%; p=0.070, FE; OR=1.75, 95% CI, 0.97-3.18). Furthermore, PON1 activity was significantly higher in nonprogressive patients compared with progressors (206 +/- 71 vs. 136 +/- 48; p<0.001), and activity significantly correlated with 1/serum creatinine (SCr) (p<0.001; r=0.38).
CONCLUSIONS: The results of this study suggest that in IgAN, lower PON1 activity may be associated with the deterioration of kidney function. This could be due to variable expression of the PON1 gene, or a functional effect of the gene product.
ESTHER : Kovacs_2006_J.Nephrol_19_732
PubMedSearch : Kovacs_2006_J.Nephrol_19_732
PubMedID: 17173245

Title : Hyperleptinemia is not responsible for decreased paraoxonase activity in hemodialysis patients - Varga_2006_Nephron.Clin.Pract_103_c114
Author(s) : Varga Z , Paragh G , Seres I , Kakuk G , Karanyi Z , Karpati I , Matyus J , Csongradi E , Juhasz A , Balla J , Bajnok L
Ref : Nephron Clin Pract , 103 :c114 , 2006
Abstract : BACKGROUND: Exogenous leptin markedly decreased plasma paraoxonase (PON1) activity in rats. Hyperleptinemia and decreased PON1 activity have previously been demonstrated in uremia. Therefore, we investigated the relationship between leptin level and PON1 activity in hemodialysis (HD) patients.
METHODS: Leptin and PON1 were determined in 40 HD patients and 40 age-matched controls with similar body mass index (BMI).
RESULTS: Leptin was higher (p < 0.001) and PON1 activity was lower (p < 0.001) in HD patients than in controls. PON1 and PON1/HDL ratio was higher in HD patients with BMI >25 kg/m2 than in HD patients with BMI <25 kg/m2. It was not due to a difference in frequency of high activity phenotype of PON1 among subgroups of HD patients. There was no similar difference in controls. Spearman analysis showed a significant correlation between leptin and PON1 activity (p < 0.02), BMI (p < 0.001), triglyceride (TG) (p < 0.03), and Kt/V (-0.323, p < 0.03), but multiparametric regression analysis did not reveal it. PON1 activity depended on BMI in both models. In controls, leptin correlated with BMI (p < 0.001) and TG (p < 0.002) but not PON1 activity. A slight decrease in leptin concentration and PON1 activity during HD was observed. CONCLUSION: Our results suggest the role of other pathophysiological conditions besides hyperleptinemia resulting in decreased PON1 activity in HD patients.
ESTHER : Varga_2006_Nephron.Clin.Pract_103_c114
PubMedSearch : Varga_2006_Nephron.Clin.Pract_103_c114
PubMedID: 16534235

Title : Correlation between the activities of lipoprotein lipase and paraoxonase in type 2 diabetes mellitus - Kalmar_2005_Diabetes.Metab_31_574
Author(s) : Kalmar T , Seres I , Balogh Z , Kaplar M , Winkler G , Paragh G
Ref : Diabetes Metab , 31 :574 , 2005
Abstract : UNLABELLED: In type 2 diabetes mellitus the decreased catabolism of triglyceride-rich lipoproteins as a consequence of mainly the decreased lipoprotein lipase activity results in hypertriglyceridaemia and other lipoprotein alterations promoting atherosclerosis. The high-density lipoprotein-associated enzyme, paraoxonase, prevents the oxidation of low-density lipoprotein, which is an antiatherogenic effect. AIM: to examine the relation between the activities of enzymes influencing HDL remodelling- LPL and PON- in type 2 diabetes mellitus.
METHODS: 56 newly diagnosed type 2 diabetic patients and 39 healthy controls were involved in the study. The serum PON activity was measured spectrophotometrically using paraoxone as substrate. PON phenotype was determined by the dual substrate method, PON mass was measured by ELISA. The determination of lipoprotein lipase activity was performed using 3H-triolein.
RESULTS: We noticed smaller PON activity decrease in our newly diagnosed diabetic subjects compared to the previous studies which investigated the alteration of enzyme activity after a longer duration of diabetes mellitus. The lipoprotein lipase activity showed a positive correlation with PON activity (r=0.43; P<0.02). Interestingly, the PON activity of the homozygous-low activity group did not correlate with the LPL activity, while in the heterozygous and homozygous-high activity groups there was a significantly positive correlation (r=0.51; P<0.05) between PON and LPL activity. CONCLUSION: Besides lipid alterations, the metabolic changes of type 2 diabetes mellitus influence the reduction of the antioxidant capacity of HDL by remodelling HDL and decreasing PON activity via modification of lipoprotein lipase activity, which might contribute to accelerated atherosclerosis.
ESTHER : Kalmar_2005_Diabetes.Metab_31_574
PubMedSearch : Kalmar_2005_Diabetes.Metab_31_574
PubMedID: 16357806

Title : [Analysis of paraoxonase activity and lipid profile in lupus patients] - Kiss_2005_Orv.Hetil_146_2395
Author(s) : Kiss E , Seres I , Zsolt K , Tarr T , Csipo I , Szegedi G , Paragh G
Ref : Orvosi Hetilap , 146 :2395 , 2005
Abstract : INTRODUCTION: Immune-inflammatory processes play important role in the pathogenesis of atherosclerosis. Therefore, increasing attention is focused on rheumatic diseases with chronic inflammation, such as systemic lupus erythematosus. Besides direct influences, inflammation may modify the development of atherosclerosis by other mechanisms. AIMS: To examine paraaoxonase activity and lipid profile in lupus patients.
METHODS: Authors entered 37 definitive lupus patients and 30 age- and sex-matched normal controls into the present study. Patients' age was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, disease activity index 2.8 +/- 3.4. Lipid parameters (total cholesterol, LDL-C, HDL-C, Apo-AI and ApoB) were determined by an autoanalyser, paraoxonase and arylesterase activities were measured spectrophotometrically. Phenotypic distribution of the enzyme was determined by dual substrate method. Anti-oxLDL was measured by ELISA method, CRP by automatised immunoassay. Statistical analysis was performed by SPSS program.
RESULTS: Despite of long disease duration and low inflammatory activity authors found significantly (p < 0.001) decreased paraoxonase activity (121.9 +/- 65.9 U/mL) (p < 0.001) in lupus as compared to control (188.1 +/- 78.9 U/mL), which correlated with the presence of atherothrombotic complications (p = 0.009). High activity BB phenotype did not occur in lupus. Lipid parameters and arylesterase activity were within normal range in both groups. No significant correlation was found between paraoxonase activity and disease activity index, dose of corticosteroid therapy, CRP and anti-oxLDL level. Arylesterase activity did not differ in lupus and control groups.
CONCLUSIONS: Present results suggest that other mechanisms, e.g. antibodies, genetic factors, alteration in the distribution of HDL-subfractions or ensyme abnormalities in HDL remodelling may stand at the background of reduced paraoxonase activity in lupus.
ESTHER : Kiss_2005_Orv.Hetil_146_2395
PubMedSearch : Kiss_2005_Orv.Hetil_146_2395
PubMedID: 16398152

Title : Study of factors influencing the decreased HDL associated PON1 activity with aging - Seres_2004_Exp.Gerontol_39_59
Author(s) : Seres I , Paragh G , Deschene E , Fulop T, Jr. , Khalil A
Ref : Experimental Gerontology , 39 :59 , 2004
Abstract : Paraoxonase (PON1) is principally complexed to HDL and is responsible, at least in part, for its antioxidant properties. PON1 activity decreases in several pathologies associated with atherosclerosis. The aim of this study was to investigate the PON1 activity and factors influencing its activity as a function of age. One hundred and twenty nine healthy subjects aged between 22 and 89 years were recruited for the study. We found that serum PON1 activity significantly decreased with age (r=-0.38, p<0.0001) while its arylesterase activity as well as its concentration in the serum did not change significantly. HDL concentrations remained unchanged with age, however, Apo A1 concentration showed a slight negative but significant correlation with age (r=-0.19, p<0.027). Moreover, the total cholesterol concentration was positively and significantly correlated with age (r=0.40, p<0.001). Thus, our results suggest that the decrease in PON1 activity cannot be explained by the decrease in Apo A1 concentrations with age. HDL from elderly subjects was more susceptible to oxidation than HDL from young subjects measured by higher lipid peroxidation rate. Thus, the decrease in PON1 activity may contribute to this increased susceptibility of HDL to oxidation with aging. Altogether our results suggest that the decrease in PON1 activity may be related to the development of oxidative stress conditions with aging and the increased HDL susceptibility to oxidation in elderly subjects.
ESTHER : Seres_2004_Exp.Gerontol_39_59
PubMedSearch : Seres_2004_Exp.Gerontol_39_59
PubMedID: 14724065

Title : Effect of short term treatment with simvastatin and atorvastatin on lipids and paraoxonase activity in patients with hyperlipoproteinaemia - Paragh_2004_Curr.Med.Res.Opin_20_1321
Author(s) : Paragh G , Torocsik D , Seres I , Harangi M , Illyes L , Balogh Z , Kovacs P
Ref : Curr Med Res Opin , 20 :1321 , 2004
Abstract : OBJECTIVE: High-density lipoprotein (HDL)-associated paraoxonase (PON) activity may play an important role in the inhibition of low-density lipoprotein (LDL) oxidation. Previous studies have demonstrated that serum PON activity is decreased in patients with hyperlipoproteinaemia and coronary heart disease. The study presented here examined the effect of short-term treatment with simvastatin and atorvastatin on lipids and PON activity in patients with hyperlipoproteinaemia. RESEARCH DESIGN AND
METHODS: A prospective, non-blinded, single-group, cross-over, comparative trial was performed. Following an 8-week dietary run-in period, 49 patients (23 men and 26 women, mean age: 59.8 +/- 7.9 years) with Fredrickson type IIa. and IIb. hyperlipoproteinaemias were randomized to receive either simvastatin 20 mg/day or atorvastatin 10 mg/day for 3 months. Following an 8-week washout period, patients were crossed-over to receive the other drug for a further 3 months. Serum lipids were measured and serum PON activity was determined spectrophotometrically using paraoxon as a substrate.
RESULTS: Simvastatin treatment significantly reduced serum cholesterol, LDL-cholesterol (LDL-C) and apolipoprotein (apo) B levels (p < 0.001). Atorvastatin had a more pronounced cholesterol, LDL-C- and apo B-lowering effect (p < 0.001) compared with simvastatin. Both statins also significantly reduced serum triglyceride levels (p < 0.01). Simvastatin and atorvastatin caused no significant change in the levels of HDL-cholesterol (HDL-C) and apo A1. HDL-associated PON activity did not change significantly after simvastatin therapy, but significantly increased after atorvastatin treatment (p < 0.05).
CONCLUSIONS: Short-term administration of simvastatin did not increase PON activity. Atorvastatin treatment had a favourable effect on lipid profile and increased the activity of HDL-associated PON.
ESTHER : Paragh_2004_Curr.Med.Res.Opin_20_1321
PubMedSearch : Paragh_2004_Curr.Med.Res.Opin_20_1321
PubMedID: 15324535

Title : Atorvastatin effect on high-density lipoprotein-associated paraoxonase activity and oxidative DNA damage - Harangi_2004_Eur.J.Clin.Pharmacol_60_685
Author(s) : Harangi M , Seres I , Varga Z , Emri G , Szilvassy Z , Paragh G , Remenyik E
Ref : European Journal of Clinical Pharmacology , 60 :685 , 2004
Abstract : OBJECTIVE: High-density lipoprotein (HDL)-associated antioxidant paraoxonase (PON) may reduce low-density lipoprotein (LDL) oxidation and prevent atherosclerosis. The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin on hydrogen-peroxide-induced DNA damage by comet assay and the correlation between oxidative DNA damage and antioxidant PON activity.
METHODS: Thirteen type-II/a hyperlipidemic patients were enrolled in the study. We examined the effect of 10 mg/day atorvastatin treatment on lipid levels and the degree of DNA damage in lymphocytes separated from hyperlipidemic patients, nitric oxide (NO), thiobarbituric acid-reactive substances (TBARS), PON levels and activity.
RESULTS: After 6 months, atorvastatin treatment significantly decreased serum cholesterol and LDL-cholesterol levels. The triglyceride level did not change, and there was no significant change in the HDL cholesterol level. The visual score characteristic to the degree of DNA damage in comet assay was significantly decreased, as well as the TBARS level, while the level of NO was non-significantly increased. PON activity and the PON/HDL ratio were significantly increased after atorvastatin treatment. There was a negative correlation between DNA damage and PON activity, as well as between DNA damage and the PON/HDL ratio before and after atorvastatin treatment. CONCLUSION: These findings show that atorvastatin treatment favorably affected the lipid profile, increasing the activity of HDL-associated PON and decreasing the cytotoxic effect of oxidative stress.
ESTHER : Harangi_2004_Eur.J.Clin.Pharmacol_60_685
PubMedSearch : Harangi_2004_Eur.J.Clin.Pharmacol_60_685
PubMedID: 15490140

Title : The effect of micronised fenofibrate on paraoxonase activity in patients with coronary heart disease - Paragh_2003_Diabetes.Metab_29_613
Author(s) : Paragh G , Seres I , Harangi M , Balogh Z , Illyes L , Boda J , Szilvassy Z , Kovacs P
Ref : Diabetes Metab , 29 :613 , 2003
Abstract : OBJECTIVE: To evaluate the effect of micronised fenofibrate on serum paraoxonase (PON) and lipoprotein levels in coronary heart disease patients with type IIb hyperlipidemia. PATIENTS AND
METHODS: Fifty-two patients were investigated for the three-month effect of 200 mg per day micronised fenofibrate on the serum enzyme activity and concentration of PON and their relationship with serum lipids, high-density lipoprotein (HDL-C) parameters.
RESULTS: Serum paraoxonase activity was lower in CHD patients with type IIb hyperlipoproteinemia. During the three-month study it was observed that following treatment with micronised fenofibrate, serum triglyceride and cholesterol levels decreased, while HDL-C increased significantly (p<0.001). Low-density lipoprotein (p<0.05) and apolipoprotein B-100 (p<0.01) decreased, while HDL constituent apolipoprotein A-I (p<0.05) increased after micronised fenofibrate treatment. The HDL-associated paraoxonase specific activity increased significantly (p<0.05). To assess whether the increased PON activity was due to elevated HDL and apoA-I level, we standardized PON activity for HDL and apoA-I concentrations. The standardized values for HDL (PON/HDL) increased (p<0.05) while the PON/apoA-I ratio did not change significantly. CONCLUSION: Three months of treatment with micronised fenofibrate is thought to normalize lipid profile and improve antioxidant status by increasing serum paraoxonase activity in these patients.
ESTHER : Paragh_2003_Diabetes.Metab_29_613
PubMedSearch : Paragh_2003_Diabetes.Metab_29_613
PubMedID: 14707891

Title : Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia - Paragh_2002_Eur.Arch.Psychiatry.Clin.Neurosci_252_63
Author(s) : Paragh G , Balla P , Katona E , Seres I , Egerhazi A , Degrell I
Ref : European Archives of Psychiatry & Clinical Neuroscience , 252 :63 , 2002
Abstract : The prevalence of Alzheimer's disease (AD) and vascular dementia (VAD) increases with aging of the population. The role of lipoproteins in the pathogenesis of AD is unclear: apoE(2) offers protection and apoE(3) is neutral, while apoE(4) promotes the development of the disease. Recently, several studies have confirmed the role of oxidative stress in the pathogenesis of AD and VAD. HDL-associated paraoxonase is one of the antioxidative enzymes that may reduce LDL oxidation. In our study, we investigated the lipid parameters of the sera and the serum paraoxonase activity in patients with AD and VAD. Lipid parameters were determined by an autoanalyzer in 30 AD patients, 40 VAD patients and 40 healthy, age-matched control (C) subjects. Paraoxonase activity was measured spectrophotometrically using paraoxon as the substrate. The phenotypic distribution of paraoxonase was determined by the dual substrate method, using paraoxon and phenylacetate as substrates. In our results, we found that most of the patients with AD had the apoE(4) isoform, consistent with other studies. In the VAD and AD patients we found significantly higher total-cholesterol compared to the control group (C: 4.71 +/- 0.89, VAD: 6.3 +/- 0.8, AD: 6.52 +/- 0.7 mmol/l; p < 0.01) and LDL-cholesterol levels (C: 2.6 +/- 0.6, VAD: 3.96 +/- 0.8, AD: 3.84 +/- 0.6 mmol/l; p < 0.001). The HDL-associated antioxidant, paraoxonase activity did not differ significantly in the patient groups, but compared to the healthy control subjects, paraoxonase activity was significantly lower in both of the patient groups (C: 188 +/- 55 U/l; AD: 131 +/- 37, VAD: 151 +/- 50 l; p < 0.05). Our results suggest that the defect in HDL-associated antioxidant capacity plays a role in the pathogenesis of Alzheimer's disease and vascular dementia.
ESTHER : Paragh_2002_Eur.Arch.Psychiatry.Clin.Neurosci_252_63
PubMedSearch : Paragh_2002_Eur.Arch.Psychiatry.Clin.Neurosci_252_63
PubMedID: 12111338

Title : Determination of DNA damage induced by oxidative stress in hyperlipidemic patients - Harangi_2002_Mutat.Res_513_17
Author(s) : Harangi M , Remenyik EE , Seres I , Varga Z , Katona E , Paragh G
Ref : Mutat Res , 513 :17 , 2002
Abstract : In the present paper, we report data on the genotoxic properties of hydrogen peroxide in polymorphonuclear neutrophils (PMNLs) separated from normolipidemic and type II/a hyperlipidemic patients. In all, 15 hyperlipidemic patients (11 female, 4 male, mean age 54.6+/-10.25 years) were involved in the study, and 7 normolipidemic patients (5 female, 2 male, mean age 53.4+/-8.07 years) served as controls. Using the comet assay, there was a significant difference in the degree of DNA damage between the two groups. The visual score characteristic of the degree of DNA damage was 350.97+/-31.31 in the hyperlipidemic group, while it was 289.5+/-29.49 in the control group (P<0.001). In the hyperlipidemic patients, a positive correlation was found between the degree of DNA damage and the basic oxidation of PMNLs (r=0.517), and the superoxide anion production of the cells stimulated with phorbolmiristate acetate (PMA) (r=0.326) and formyl-Met-Leu-Phe (FMLP) (r=0.525) as well. There was a negative correlation between DNA damage and HDL-associated antioxidant paraoxonase (PON) activity (r=-0.469), and the PON/HDL ratio (r=-0.631). No correlation was found between the degree of DNA damage and the plasma concentration of nitric oxide (NO) (r=0.098) and thiobarbituric acid-reactive substances (TBARS) (r=0.061) in hyperlipidemic patients. Our results show that in hyperlipidemic patients there is an increase in lymphocyte DNA damage caused by oxidative stress when compared to normolipidemic individuals as demonstrated by comet assay. Decreased antioxidant capacity in hyperlipidemic patients may play a significant role in this process.
ESTHER : Harangi_2002_Mutat.Res_513_17
PubMedSearch : Harangi_2002_Mutat.Res_513_17
PubMedID: 11719086

Title : [Changes in lipid profile and paraoxonase activity in obese patients as a result of orlistat treatment] - Audikovszky_2001_Orv.Hetil_142_2779
Author(s) : Audikovszky M , Pados G , Seres I , Harangi M , Fulop P , Katona E , Winkler G , Paragh G
Ref : Orvosi Hetilap , 142 :2779 , 2001
Abstract : 257 patients from 33 centres were involved in a six-month study, the aim of which was to assess the effect of orlistat together with a diet. The authors examined how the treatment effected the anthropometrical and lipid parameters, extending the study to the aspect of paraoxonase activity in case of 25 patients. 44 patients dropped out during the study period due to the lack of sufficient diet compliance, whereas 3 patients had to stop the therapy because of the adverse event of flatus with discharge. On the average, the body mass of the patients decreased from 100.8 +/- 18.9 to 91.3 +/- 18.6 kg, i.e. by 9.5 kgs, while their BMI was reduced from 36.1 +/- 5.6 to 32.5 +/- 5.2 kg/m2 and the circumference of the waist changing from 119.1 +/- 20 to 108.3 +/- 15.1 cm, i.e. by 10.8 cms. The blood sugar level significantly decreased from 5.7 to 5.4, while the cholesterol concentration significantly dropped from 5.9 to 5.5, the triglyceride level being reduced from 2.4 to 2.1 mmol/l and blood pressure falling significantly from 136.6/86.9 to 129.9/81.6. All the above changes showed a significant decrease. However, the HDL-cholesterol level did not change. The serum paraoxonase activity significantly increased (143 +/- 49 vs 166 +/- 43 UL) along with the standardised values for HDL (PON/HDL), even compared to the control diet group. From the above results it may be concluded that orlistat tends to have an antioxidant effect.
ESTHER : Audikovszky_2001_Orv.Hetil_142_2779
PubMedSearch : Audikovszky_2001_Orv.Hetil_142_2779
PubMedID: 11820148

Title : Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates? - Balogh_2001_Diabetes.Metab_27_604
Author(s) : Balogh Z , Seres I , Harangi M , Kovacs P , Kakuk G , Paragh G
Ref : Diabetes Metab , 27 :604 , 2001
Abstract : OBJECTIVE: The constellation of elevated triglycerides and decreased high-density lipoprotein is recognised as a risk factor for CAD and constitutes the major dyslipidemia in type 2 diabetes. The high-density lipoprotein associated paraoxonase activity can inhibit low-density lipoprotein oxidation and has an antiatherogenic effect. To determine the effect of gemfibrozil on the dyslipidemia and serum paraoxonase activity in patients with type 2 diabetes. MATERIAL AND
METHODS: Fifty-six type 2 diabetic patients with associated hypertriglyceridemia were involved. They were investigated for the effect of twice daily 600 mg of gemfibrozil on serum cholesterol, triglycerides, apolipoproteins, fibrinogen level, body mass index and glycated hemoglobin. Serum paraoxonase activity was measured spectrophotometrically.
RESULTS: After three months, it was observed that under the effect of gemfibrozil, serum triglyceride level was significantly decreased (from median: 3.46 mmol/l quartiles: q1=2.92 q3=5.28 to median 2.20 mmol/l quartiles: q1=1.79 q3=3.65; p<0.001) while protective high-density lipoprotein (from 1.02 +/- 0.22 mmol/l to 1.13 +/- 0.28 mmol/l; p=0.05) and apolipoprotein A(1) (from 1.56 +/- 0.33 g/l to 1.72 +/- 0.29; p<0.01) levels were significantly increased. Serum paraoxonase activity was found to be significantly increased (from median: 100.2 U/l quartiles: q1=60.1 q3=152.7 to median 118.7 U/l quartiles: q1=80.1 q3=171.0; p<0.001) after gemfibrozil treatment. The total cholesterol, low-density lipoprotein, apolipoprotein B, lipoprotein (a), glycated hemoglobin and fibrinogen levels were not significantly changed during the three-month treatment period. The standardized paraoxonase activity for HDL and apo A(1) were not significantly changed. Paraoxonase activity did not correlate with the concentration of glycohemoglobin and the duration of diabetes. CONCLUSION: Twice daily administration of 600 mg of gemfibrozil is effective in type 2 diabetic patients with associated hypertriglyceridemia. It favorably lowers lipid levels, and improves antioxidant status by increasing serum paraoxonase activity.
ESTHER : Balogh_2001_Diabetes.Metab_27_604
PubMedSearch : Balogh_2001_Diabetes.Metab_27_604
PubMedID: 11694861

Title : Serum paraoxonase activity changes in uremic and kidney-transplanted patients - Paragh_1999_Nephron_83_126
Author(s) : Paragh G , Asztalos L , Seres I , Balogh Z , Locsey L , Karpati I , Matyus J , Katona E , Harangi M , Kakuk G
Ref : Nephron , 83 :126 , 1999
Abstract : Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36+/-30. 12 vs. control 188.05+/-58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5+/-35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7+/-54.8) and kidney-transplanted patients (144.5+/-32.7) when compared to controls (194.5+/-94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31. 62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.
ESTHER : Paragh_1999_Nephron_83_126
PubMedSearch : Paragh_1999_Nephron_83_126
PubMedID: 10516491

Title : The serum paraoxonase activity in patients with chronic renal failure and hyperlipidemia - Paragh_1998_Nephron_80_166
Author(s) : Paragh G , Seres I , Balogh Z , Varga Z , Karpati I , Matyus J , Ujhelyi L , Kakuk G
Ref : Nephron , 80 :166 , 1998
Abstract : Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A1) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A1 levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A1 level decreases, we standardized the enzyme activity for HDL and Apo-A1 concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 +/- 69.5) as compared with hyperlipidemic patients (137.64 +/- 81.0) and controls (194.45 +/- 94.45). The standardized values for Apo-A1 showed a similar tendency: paraoxonase/Apo-A1 ratio in uremic patients 89.64 +/- 47.8, in hyperlipidemic patients 128.12 +/- 69.83, and in controls 161.40 +/- 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.
ESTHER : Paragh_1998_Nephron_80_166
PubMedSearch : Paragh_1998_Nephron_80_166
PubMedID: 9736814