Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. Arylesterase activity and antioxidant status depend on PON1-Q192R and PON1-L55M polymorphisms in subjects with increased risk of cardiovascular disease consuming walnut-enriched meat. Phytotherapy in a rat model of hyperoxaluria: the antioxidant effects of quercetin involve serum paraoxonase 1 activation Simvastatin Modulates Expression of the PON1 Gene and Increases Serum Paraoxonase: A Role for Sterol Regulatory Element–Binding Protein-2 Effect of Simvastatin Therapy on Paraoxonase Activity and Related Lipoproteins in Familial Hypercholesterolemic Patients Paraoxonase-1 is a major determinant of clopidogrel efficacy Paraoxonase 1 Activity in Chylomicrons and VLDL: The Effect of Type 2 Diabetes and Meals Rich in Saturated Fat and Oleic Acid Effect of the nutritional supplement ALAnerv® on the serum PON1 activity in post-acute stroke patients. Effect of fish oil supplements on serum paraoxonase activity in female patients with rheumatoid arthritis: a double-blind randomized controlled trial. Antioxidant effect of atorvastatin is independent of PON1 gene T(–107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients Benefits of omega-3 Fatty acids supplementation on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome. Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia. Alpha-tocopherol supplementation prevents the exercise-induced reduction of serum paraoxonase 1/arylesterase activities in healthy individuals Paraoxonase 1 Q192R (PON1–192) polymorphism is associated with reduced lipid peroxidation in R-allele-carrier but not in QQ homozygous elderly subjects on a tomato-rich diet Interaction between the Gln-Arg 192 variants of the paraoxonase gene and oleic acid intake as a determinant of high-density lipoprotein cholesterol and paraoxonase activity. Dietary modifications and gene polymorphisms alter serum paraoxonase activity in healthy women. Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: Intervention study in healthy men. Atorvastatin Preferentially Reduces LDL-Associated Platelet-Activating Factor Acetylhydrolase Activity in Dyslipidemias of Type IIA and Type IIB Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin. Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players. Low Paraoxonase Activity Predicts Coronary Events in the Caerphilly Prospective Study
CONTEXT Paraoxonase 1 ( PON1 ) is reported to have antioxidant and cardioprotective properties . The relationship between PON1 genotypes and functional activity with systemic measures of oxidative stress and cardiovascular disease ( CVD ) risk in humans has not been systematic ally investigated . OBJECTIVE To investigate the relationship of genetic and biochemical determinants of PON1 activity with systemic measures of oxidative stress and CVD risk in humans . DESIGN , SETTING , AND PARTICIPANTS The association between systemic PON1 activity measures and a functional polymorphism ( Q192R ) result ing in high PON1 activity with prevalent CVD and future major adverse cardiac events ( myocardial infa rct ion , stroke , or death ) was evaluated in 1399 sequential consenting patients undergoing diagnostic coronary angiography between September 2002 and November 2003 at the Clevel and Clinic . Patients were followed up until December 2006 . Systemic levels of multiple structurally defined fatty acid oxidation products were also measured by mass spectrometry in 150 age- , sex- , and race-matched patients and compared with regard to PON1 genotype and activity . MAIN OUTCOME MEASURES Relationship between a functional PON1 polymorphism and PON1 activity with global indices of systemic oxidative stress and risk of CVD . RESULTS The PON1 genotype demonstrated significant dose-dependent associations ( QQ192 > QR192 > RR192 ) with decreased levels of serum PON1 activity and with increased levels of systemic indices of oxidative stress . Compared with participants with either the PON1 RR192 or QR192 genotype , participants with the QQ192 genotype demonstrated an increased risk of all-cause mortality ( 43/681 deaths [ 6.75 % ] in RR192 and QR192 and 62/584 deaths [ 11.1 % ] in QQ192 ; adjusted hazard ratio , 2.05 ; 95 % confidence interval [ CI ] , 1.32 - 3.18 ) and of major adverse cardiac events ( 88/681 events [ 13.6 % ] in RR192 and QR192 and 102/584 events [ 18.0 % ] in QQ192 ; adjusted hazard ratio , 1.48 ; 95 % CI , 1.09 - 2.03 ; P = .01 ) . The incidence of major adverse cardiac events was significantly lower in participants in the highest PON1 activity quartile ( 23/315 [ 7.3 % ] ) and 235/324 [ 7.7 % ] for paraoxonase and arylesterase , respectively ) compared with those in the lowest activity quartile ( 78/311 [ 25.1 % ] and 75/319 [ 23.5 % ] ; P < .001 for paraoxonase and arylesterase , respectively ) . The adjusted hazard ratios for major adverse cardiac events between the highest and lowest PON1 activity quartiles were , for paraoxonase , 3.4 ( 95 % CI , 2.1 - 5.5 ; P < .001 ) and for arylesterase , 2.9 ( 95 % CI , 1.8 - 4.7 ; P < .001 ) and remained independent in multivariate analysis . CONCLUSION This study provides direct evidence for a mechanistic link between genetic determinants and activity of PON1 with systemic oxidative stress and prospect i ve cardiovascular risk , indicating a potential mechanism for the atheroprotective function of PON1 Human paraoxonase ( PON1 ) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation . The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease ( CVD ) , taking into account the effects of PON1-Q192R and PON1-L55 M polymorphisms on 1 ) basal serum arylesterase activity , lipid peroxidation ( LPO ) , and LDL-cholesterol ( LDL-C ) , HDL-C , total cholesterol ( TC ) , and oxidized-LDL ( ox-LDL ) concentrations ; 2 ) the relations between arylesterase activity and lipid variables ; and 3 ) the effect of walnut-enriched meat ( WM ) consumption on arylesterase activity and lipid variables .  Twenty-three Caucasians at increased risk of CVD were r and omly assigned to diet order groups in a crossover , nonblinded , placebo-controlled trial , consisting of two 5-wk experimental periods [ WM and control meat ( CM ) ] . Significant PON1-L55 M x PON1-Q192R interactions affected basal serum HDL-C ( P = 0.019 ) , LDL-C ( P = 0.028 ) and TC ( P = 0.022 ) and tended to affect arylesterase activity ( P = 0.083 ) . Basal arylesterase activity was positively correlated with basal HDL-C ( r = 0.53 ; P < 0.05 ) and TC ( r = 0.43 ; P < 0.05 ) and negatively correlated with LPO ( r = -0.70 ; P < 0.01 ) and the ox-LDL : LDL ratio ( r = -0.63 ; P < 0.01 ) . WM decreased arylesterase activity in PON1 - 55 M carriers ( P = 0.012 ) but not in PON1-L55 individuals , and decreased LPO concentrations in PON1 - 192R carriers ( P = 0.031 ) but not in PON1-Q192 subjects . To conclude , serum TC , HDL-C , and LDL-C concentrations and arylesterase activity depend on the interaction of PON1-L55 M and PON1-Q192R polymorphisms . However , the PON1-Q192R polymorphism is more closely related to antioxidant status . Both polymorphisms modulate the effect of WM consumption on CVD biomarkers Serum paraoxonase 1 ( PON1 ) has been reported to be an important contributor to the antioxidant and anti-inflammatory activities of HDL , avoiding LDL oxidation . The activity of this enzyme is reduced in patients with renal insufficiency , caused by elevated oxidative stress and disturbances of apolipoprotein metabolism . Therapeutic utilization of antioxidants to control renal oxidative stress may be an effective therapy in renal protection . The aim was to investigate the protective effects of several antioxidant compounds against the oxidative stress associated to renal failure induced by ethylene glycol ( EG ) , focusing on the possible role of serum PON1 activity . Fifty-four male Wistar rats were r and omly assigned to six groups ( n = 9 ) : an untreated control ( C ) group , an EG-treated group , a catechin (CAT)-treated group , an epicatechin (EPI)-treated group , a quercetin (QUE)-treated group and a folk herbal extract (FHE)-treated group . After 16 d of treatment , calcium oxalate lithiasis was induced in the rats using EG . After eight days ( treatment + EG ) , the animals were sacrificed . EG treatment impaired kidney composition , increased oxidative damage , and decreased serum paraoxonase and arylesterase activities . CAT , QUE and the FHE Fagolitos improved oxidative status by enhancing antioxidant defenses – superoxide dismutase and PON1 activities – and reducing oxidative damage , thus reinforcing the idea of a possible role of PON1 in the protective effects of QUE against the deleterious consequences of oxidative stress in kidney Background —The HDL-associated enzyme paraoxonase protects LDLs from oxidative stress . 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) appear to favorably influence the atherosclerotic process by different mechanisms . The present study examined the influence of simvastatin on paraoxonase expression and serum paraoxonase levels . Methods and Results —Simvastatin upregulated in a dose-dependent manner the activity of the promoter of the paraoxonase gene in expression cassettes transfected into HepG2 cells . Upregulation could be blocked by mevalonate and other intermediates of the cholesterol biosynthetic pathway . Simvastatin increased nuclear factors , notably sterol regulatory element – binding protein-2 , capable of binding to the paraoxonase promoter ; this was also blocked by mevalonate . Sterol regulatory element – binding protein-2 upregulated promoter activity in vitro . Patients treated with statin  showed a significant increase in serum concentrations and activities of paraoxonase . Conclusions —The data indicate that simvastatin can modulate expression in vitro of the antioxidant enzyme paraoxonase and is associated with increased serum paraoxonase concentration and activity . It is consistent with effects of simvastatin treatment , which have the potential to influence beneficially antiatherogenic mechanisms at the HDL level . The study provides evidence for 1 molecular mechanism by which paraoxonase gene expression could be regulated Human paraoxonase ( PON1 ) is a calcium-dependent esterase closely associated with high density lipoprotein (HDL)-containing apolipoprotein AI ( apoAI ) , which has been shown to confer antioxidant properties to HDL . PON1 has been recently implicated in the pathogenesis of atherosclerosis . Low PON1 activities have been found in familial hypercholesterolemia ( FH ) and diabetes mellitus . We have undertaken a study of the effect of the lipid-lowering drug simvastatin on serum PON1 activity ( in relation to paraoxon and arylesterase activity ) , on apoAI-containing and apolipoprotein B (apoB)-containing lipoproteins , and on lipid peroxide concentrations in 64 ( 39 women and 25 men ) unrelated FH patients . We have also analyzed the influence of the PON1 - 192 and PON1 - 55 genetic polymorphisms on the response of PON1 activity to simvastatin therapy . A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken . The major effect of simvastatin on lipid traits was to decrease serum cholesterol , low density lipoprotein ( LDL ) cholesterol , and lipid peroxide concentrations by 19.9 % , 26.3 % , and 37.3 % , respectively . There was also a significant decrease in serum apoB , LDL apoB , and triglyceride concentrations ( 20.5 % , 21.1 % , and 15.6 % , respectively ) . Conversely , simvastatin had no significant influence on very low density lipoprotein – lipid content , HDL cholesterol , apoAI concentrations , and lipoprotein AI and AI : AII particles . Remarkably , serum PON1 activity toward paraoxon significantly increased during treatment with simvastatin ( 168.7±100.3 U/L before therapy versus 189.5±116.5 U/L after therapy , P = 0.005 ) . Arylesterase activity displayed only a nonsignificant trend to increase after therapy . Whereas PON1 activity levels were significantly lower in FH patients  before simvastatin therapy compared with those of 124 normolipidemic subjects ( 168.7±100.3 versus 207.6±125.2 U/L , respectively;P < 0.05 ) , this difference disappeared after simvastatin therapy . After simvastatin therapy , a significantly negative correlation between PON1 activity and lipid peroxide concentration was observed ( r = −0.35 , P = 0.028 ) . The latter also strongly correlated with LDL cholesterol concentration ( r = 0.64 , P < 0.001 ) . Serum PON1 activity levels were significantly lower in the low-activity PON1 - 192 QQ and PON1 - 55 M carriers than in R carriers and in LL carriers , respectively . No significant differences were found in the therapeutic response of PON1 activity between genotype groups ( 8.5 % and 11.1 % increase for QQ homozygous and R-carrier FH patients , respectively , and 12.7 % and 9.5 % increase for LL homozygotes and M carriers , respectively ) . We conclude that simvastatin may have important antioxidant properties through increasing serum PON1 activity , perhaps as a consequence of reducing oxidative stress , by a mechanism independent of apoAI-containing lipoprotein concentration and without the influence of PON1 - 192 and PON1 - 55 genetic polymorphisms . Further studies are clearly warranted to clarify the precise mechanism by which simvastatin therapy is associated with increased PON1 activity Clinical efficacy of the antiplatelet drug clopidogrel is hampered by its variable biotransformation into the active metabolite . The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors , but the specific genes and mechanisms underlying clopidogrel bioactivation remain unclear . Using in vitro metabolomic profiling techniques , we identified paraoxonase-1 ( PON1 ) as the crucial enzyme for clopidogrel bioactivation , with its common Q192R polymorphism determining the rate of active metabolite formation . We tested the clinical relevance of the PON1 Q192R genotype in a population of individuals with coronary artery disease who underwent stent implantation and received clopidogrel therapy .  PON1 QQ192 homozygous individuals showed a considerably higher risk than RR192 homozygous individuals of stent thrombosis , lower PON1 plasma activity , lower plasma concentrations of active metabolite and lower platelet inhibition . Thus , we identified PON1 as a key factor for the bioactivation and clinical activity of clopidogrel . These findings have therapeutic implication s and may be exploited to prospect ively assess the clinical efficacy of clopidogrel Paraoxonase 1 ( PON 1 ) has antioxidant and cardioprotective properties and is abnormally low in type 2 diabetic serum . This study aim ed to determine the effect of type 2 diabetes and meals rich in saturated fat and oleic acid on PON1 activity in chylomicrons and very low density lipoproteins ( VLDL ) . PON1 arylesterase activity was measured in chylomicrons and VLDL that were isolated in serum from 20 patients with type 2 diabetes and 20 age- and gender-matched , overweight controls 3 h after meals rich in cream or olive oil in a r and omized , cross-over study . Chylomicron – PON1 activity ( 45 % , P = 0.02 ) , ratio chylomicron – PON1/chylomicron – triacylglycerides ( TAG ) ( 42 % , P = 0.03 ) and chylomicron – protein content ( 46 % , P < 0.001 ) were significantly lower in patients with type 2 diabetes compared with controls after the olive oil meal with comparable findings after the meal rich in cream . After ingestion of olive oil , chylomicron – PON1 activity was significantly higher in controls ( P = 0.01 ) and marginally higher ( P = 0.06 ) in diabetic patients and chylomicron – TAG were significantly ( P < 0 . 05 ) higher in both groups of subjects , compared with values after ingestion of cream . VLDL – PON1 increased ( two-fold ) significantly ( P < 0.003 ) during both meals . Chylomicron-PON1 activity was correlated significantly with chylomicron – protein ( P < 0.001 , n = 40 ) and with postpr and ial serum PON1 activity ( P ≤ 0.001 , n = 40 ) . Our data suggest that type 2 diabetes is associated with abnormally low chylomicron – PON1 activity after fatty meals and this may be linked to lower chylomicron – protein content and serum PON1 activity . Switching from saturated fat to olive oil in the meal increases PON1 activity in the chylomicron fraction largely due to increased numbers of chylomicron particles BACKGROUND Paraoxonase-1 ( PON1 ) is one of the HDL-associated proteins which contributes to the antioxidant properties of these lipoproteins . The aim of this pilot study was to evaluate the effect of the nutritional supplement ALAnerv ® on serum PON1 activity in post-acute stroke patients undergoing rehabilitation . METHODS We enrolled 28 post-acute stroke patients and r and omly divided them into ( - ) ALA or ( + ) ALA study groups . All the patients underwent the same rehabilitation program and received comparable st and ard medications . Moreover , ( + ) ALA patients received ALAnerv ® for two weeks ( 2 pills/day ) . The serum PON1 activity was assessed on blood sample s taken at the admission and at the discharge moments , respectively . We used paraoxon ( paraoxonase activity , PONA ) , phenyl acetate ( arylesterase activity , ARYLA ) and dihydrocoumarin ( lactonase activity , LACTA ) as substrates , the latter activity being regarded as physiologically relevant . A control group of 14 apparently healthy subjects was also created . RESULTS In the ( + ) ALA group , LACTA significantly increased during the study period ( 17.6 ± 3.2 vs. 27.6 ± 3.5 , p = 0.002 ) . Moreover , the percentage of LACTA variation between ( - ) ALA and ( + ) ALA groups during the study was also statistically different ( -11.7 ± 6.9 % vs. + 95.1 ± 29.7 % , p < 0.0001 ) . CONCLUSIONS These preliminary results suggest that ALA nerv ® could contribute to the improvement of the physiologically relevant LACTA of PON1 in post-acute stroke patients , enabling this enzyme to contribute to the redox correction . Also , this study raises the question about the effect of a longer treatment period over the other enzymatic activities of serum PON1 BACKGROUND This study was conducted to determine the effect of fish oil ( FO ) supplements on high density lipoprotein cholesterol ( HDL-C ) , apolipoprotein-AI ( Apo-AI ) , malondialdehyde ( MDA ) , arylesterase ( Aryl ) , and paraoxonase-1 ( PON1 ) activity in female patients with rheumatoid arthritis ( RA ) . METHODS A total of 90 RA patients were r and omly allocated into two groups that were treated with one FO pearl ( 1 gr ) daily or placebo for three months in addition to conventional treatment .  HDL-C , Apo-AI , and MDA levels as well as PON1 and Aryl activities were measured before and after treatment . Independent t-test was used to match basal parameters of case and control groups . Paired t-test was used to assess significance of the differences . Correlation was evaluated by Pearsons test and the statistical significance was set at P < 0.05 . RESULTS No significant differences were noted between FO and placebo patients with regards to age , disease duration , post-menopausal status , conventional therapy , body mass index ( BMI ) , and numbers of swollen and tender joints at the beginning of the study . There were 83 patients who completed the three-month follow up . Serum levels of HDL-C ( P = 0.018 ) , Apo-AI ( P = 0.165 ) , Aryl ( P = 0.026 ) , and PON1 ( P = 0.049 ) activity increased , whereas MDA levels decreased significantly with FO supplementation ( P = 0.077 ) . Significant correlations between increased PON1 activity and both HDL-C ( P = 0.007 , r = 0.419 ) and Apo-AI ( P < 0.001 , r = 0.742 ) concentrations as well as between HDL-C and Apo AI levels ( P = 0.01 , r = 0.403 ) were found . CONCLUSION According to the results of this study , FO could increase serum HDL-C and PON1 levels and Aryl activity in female patients with RA ABSTRACT Background : Serum paraoxonase ( PON1 ) , a high density lipoprotein (HDL)-bound antioxidant enzyme , plays a role in atherosclerosis . An increase in PON1 activity has been reported following statin treatment . Objective : In the present study the following factors were evaluated : the influence of PON1 gene Q192R , L55 M and T(–107)C polymorphisms on the response of LDL oxidisability and PON1 activity to atorvastatin treatment . Research design and methods : 205 Sicilian subjects with primary hypercholesterolaemia ( HCh ) and 69 healthy subjects as controls were concurrently enrolled . Hypercholesterolaemic patients were r and omly divided into two groups : an atorvastatin group ( 10 mg/day atorvastatin ) and a placebo group .  Lipid profile , markers of LDL resistance to in vitro oxidation ( lag-phase , oxidation rate and thiobarbituric acid-reactive substances ) , vitamin E content in LDL , PON1 activity and genotypes in both HCh and control subjects were determined at baseline . The same parameters were measured again after 3 weeks of treatment in both the atorvastatin and placebo groups . Results : HCh subjects showed significantly lower LDL resistance to oxidation , vitamin E content and PON1 activity levels than controls . A strong association was found among PON1 T(–107)C genotypes , LDL susceptibility to oxidation , vitamin E content and PON1 activity . After treatment , the atorvastatin group displayed a significant decrease in total cholesterol , LDL-cholesterol levels , and LDL susceptibility to oxidation , and an increase in vitamin E content and PON1 activity , compared with baseline values . Unlike PON1 activity levels , no difference among PON1 gene polymorphisms and reduction in markers of LDL oxidisability was observed . Conclusions : These results show , for the first time , that atorvastatin is able to improve the resistance to LDL oxidation independently of PON1 gene polymorphism BACKGROUND Polycystic ovary syndrome ( PCOS ) is a common endocrine disorder associated with increased risk of cardiovascular disease . The purpose of this study was to investigate the ef¬fects of omega-3 fatty acids on serum paraoxonase 1 activity and lipids ratios in polycystic ovary syndrome . METHODS This double-blind r and omized controlled clinical trial was conducted on 64 PCOS pa¬tients with 20 - 35 years old . Thirty two of the subjects had taken 4 g/day omega -3 fatty acids and 32 patients were given placebo for 8 weeks . Fasting blood sample s , anthropometric measure¬ments and dietary intakes were collected at the beginning and the end of the study . Serum total cholesterol , triglyceride , and HDL-C were measured using the enzymatic methods . LDL-C con¬centration was calculated by the Friedewald formula and arylesterase activity of serum PON1 was measured . Data were analyzed using SPSS software . RESULTS Omega-3 fatty acids significantly decreased TC/HDL-C and LDL-C/HDL-C ratios ( P = 0.009 for both ) and significantly increased serum PON1 activity ( P = 0.048 ) compared with placebo . Changes in TG/HDL-C ratio were not statistically significant in omega-3 fatty acids group at the end of the study in comparison to placebo group . Reduction in TC/HDL-C , LDL-C/HDL-C and TG/HDL-C ratios and increase in serum PON1 activity were also significant in omega-3 fatty acids group at the end of the study compared with baseline values ( P < 0.001 , P < 0.001 , P = 0.004 , and P = 0.001 , respectively ) . CONCLUSION Omega-3 fatty acids may decrease the risk for cardiovascular disease through the improvement in paraxonase-1 activity and reduction in some lipids ratio in PCOS women CONTEXT AND OBJECTIVE Paraoxonase 1 ( PON1 ) , an enzyme associated with high-density lipoprotein ( HDL-PON1 ) , is reported to have antioxidant and cardioprotective properties . The aim of the present study was to investigate the effects of anthocyanins on the HDL-PON1 activity and cholesterol efflux capacity in hypercholesterolemic subjects . DESIGN AND PARTICIPANTS A total of 122 hypercholesterolemic subjects were given 160 mg of anthocyanins twice daily or placebo ( n = 61 of each group ) for 24 weeks in a double-blind , r and omized , placebo-controlled trial . Participants and investigators were masked to treatment allocation . RESULTS Anthocyanin consumption significantly increased HDL cholesterol and decreased low -density lipoprotein cholesterol concentrations compared with placebo ( P < .018 and P < .001 , respectively ) . Anthocyanin supplementation also increased the activity of HDL-PON1 compared with placebo ( P < .001 ) . Furthermore , cholesterol efflux capacity was increased more in the anthocyanin group ( 20.0 % increase ) than in the placebo group ( 0.2 % increase ) ( P < .001 ) . The negative correlations established between HDL-PON1 activity and the levels of lipid hydroperoxides associated with HDL confirm the relationship between PON1 activity and lipid peroxidation of lipoproteins . Furthermore , a strong positive correlation was noted between increased HDL-PON1 activity and improved cholesterol efflux capacity both before and after adjustment for HDL cholesterol and apolipoprotein AI in anthocyanin-treated subjects ( both P < .001 ) . Inhibition of HDL-PON1 activity strongly prevented the antioxidant ability of HDL and attenuated the cholesterol efflux capacity of subjects from anthocyanin group . CONCLUSIONS Our observations suggest that the alterations of PON1 activity by anthocyanin observed in hypercholesterolemic HDL reflect a shift to an improvement of cholesterol efflux capacity of HDL and may provide a link between anthocyanin and cardioprotective effects Objective : To investigate PON 1/Aryl activities in basketball players with or without α-T supplementation pre- and post-training .  Vitamin E ( α-tocopherol , α-T ) reduces lipid peroxidation . Paraoxonase 1/arylesterase ( PON 1/Aryl ) activities are closely related to oxidation and atherogenesis . Subject/ Methods : Blood was obtained from 10 players pre- ( group A ) , post-exercise ( group B ) and after 1 month on α-T ( 200 mg per 24 h orally ) supplementation pre- ( group C ) and post-exercise ( group D ) . Lactate , pyruvate , muscle enzyme activities , creatine kinase , lactate dehydrogenase and total antioxidant status ( TAS ) were measured with commercial kits . Catecholamines and α-T were determined with high-performance liquid chromatography methods and PON 1/Aryl activities spectrophotometrically . Results : Lactate , pyruvate , muscle enzyme activities and catecholamines were increased ( P<0.001 ) in all groups post-training . Alpha-T levels remained unaltered pre- vs post-exercise . TAS was decreased in all the groups post training . PON 1/Aryl activities were significantly decreased post-exercise ( group B ) ( PON1 : 65±12 U min−1 ml−1 , Aryl : 58±14 KU min−1 ml−1 ) as compared to those pre-exercise ( group A ) ( PON1 : 142±16 U min−1 ml−1 , Aryl : 114±12 KU min−1 ml−1 , P<0.001 ) . In contrast , the studied enzyme activities remained practically unaltered after α-T supplementation pre- vs post-training . Both enzyme activities positively correlated to TAS ( r=0.60 , P<0.001 ) . Conclusions : Alpha-T supplementation may result in protection of the enzyme PON 1/Aryl activities from free radical production Summary . Background : The oxidative modification of LDL is considered to play a central role in the pathogenesis of atherosclerosis and coronary heart disease ( CHD ) . Paraoxonase ( PON1 ) protects LDL from oxidation and may therefore retard the developement of atherosclerosis . The PON1–192 polymorphism is associated with diminished PON1 concentrations and an increased risk for CHD in RR-allele subjects . Aim of the study : To investigate the effect of tomato juice consumption on PON1 activity and other parameters related to oxidative stress in healthy elderly subjects . Furthermore , the PON1–192 genotype has been determined in the volunteers in order to see whether possible treatment effects are related to the PON1–192 polymorphism . Methods : Fifty elderly subjects were r and omly assigned to control ( mineral water ) or intervention group ( tomato juice ) . Subjects of the tomato juice group consumed daily 330 mL tomato juice for 8 weeks . Antioxidant status was measured as LDL oxidation , plasma malondialdehyde , ferric reducing ability of plasma ( FRAP ) and PON1 activity . The PON1–192 polymorphism was determined by restriction fragment length polymorphism polymerase chain reaction ( RFLP-PCR ) . Plasma carotenoids were analyzed by HPLC . Results : Tomato juice consumption  reduced LDL-oxidation and improved antioxidant status in R-allele carriers , but not in the QQ genotype group . PON1 activity increased irrespective of the genotype in both , control and intervention group . Conclusions : The changes in antioxidant status after tomato juice consumption seem to depend on the PON1–192 genotype . Healthy elderly , carrying the R-allele , could specificly reduce their higher cardiovascular risk by changing dietary habits Olive oil , rich in oleic acid , could play a particular beneficial role in the anti-atherogenic effects attributed to the Mediterranean diet . Paraoxonase ( PON1 ) has emerged as the component of high-density lipoproteins ( HDL ) most likely to explain its ability to attenuate the oxidation of low-density lipoproteins . We hypothesised that oleic acid intake might be associated with changes in PON1-HDL associated particles , and investigated the impact , if any , on this association of the PON1 - 192 polymorphism , a common polymorphism that strongly modulates PON1 activity . Six hundred and fifty-four men r and omly selected from the census were studied .  Oleic acid intake  was calculated from a 72-h recall question naire with specific software . Oleic acid intake groups ( low vs. high ) were created by stratifying the population according the median value as a cut-point . After adjusting for confounding variables , high oleic acid intake was associated with increased HDL cholesterol levels and PON1 activity only in subjects with the QR and the RR genotypes , respectively . Analyses of the variance showed a statistically significant interaction between PON1 - 192 genotypes and  oleic acid intake for log PON1 activity ( P=0.005 ) and a marginally significant interaction for HDL cholesterol ( P=0.066 ) . These results suggest that the beneficial effect of increasing oleic acid intake on HDL and PON1 activity at population level is especially observed in subjects carrying the R allele of the PON1 - 192 polymorphism Paraoxonase-1 ( PON1 ) , a HDL-associated enzyme , may protect against the development of atherosclerosis . Serum PON1 activity and PON1-mediated capacity of HDL to prevent lipoprotein oxidation are modulated by two common polymorphisms at positions 192 ( Gln-->Arg ) and 55 ( Leu-->Met ) of the PON1 gene . We studied the effect of dietary modifications on PON1 activity and the role of PON1 gene polymorphisms in the response . A controlled , crossover dietary intervention of two 5-wk periods was conducted in 37 healthy , nonsmoking women . The two study diets were either low or high in vegetables , and thus in natural antioxidants , with some differences in fatty acid contents . The mean plasma total ( -8 % , P < 0.001 ) , LDL ( -7 % , P < 0.01 ) and HDL ( -7 % , P < 0.001 % ) cholesterol , and apolipoprotein A-I ( -8 % , P < 0.001 ) concentrations were lower after the high vegetable diet period than after the low vegetable diet period . Also , the serum PON1 activity was lower ( P < 0.05 ) after the high vegetable compared with the low vegetable diet period . The reduction of PON1 activity correlated with the reduction in HDL cholesterol ( r = 0.35 , P < 0.05 ) . High baseline PON1 activity was related to the presence of the PON1(192Arg ) allele ( P < 0.001 ) and PON1(55Leu/Leu ) genotype ( P < 0.001 ) . The reduction of PON1 activity due to the high vegetable diet was greatest among the women with the PON1(192Arg ) allele ( P < 0.05 ) and PON1(55Leu/Leu ) genotype ( P < 0.05 ) . In conclusion , a diet high in vegetables , berries and fruit reduces PON1 activity , and the response is modulated by the genetic variance of PON1 BACKGROUND AND AIM Due to its high antioxidant and mono- and polyunsaturated fatty acid content virgin argan oil ( VAO ) could play a beneficial role in cardiovascular prevention . We were therefore interested in determining whether the consumption of VAO could improve plasma paraoxonase ( PON1 ) activities and antioxidant status in healthy men . METHODS AND RESULTS Sixty young men were included in this interventional study . They were given a controlled diet for 2 weeks as baseline and then received 25 g/day of butter . The group was r and omised to two diet group periods of 3 weeks each . The VAO group received 25 ml/day of oil and the extra virgin olive oil ( EVO ) group received the same quantity of EVO as control group . Plasma PON1 activities , antioxidant vitamins and LDL susceptibility to oxidation were measured . The analysis of the results shows that PON1 activities increase significantly in both groups and that lipoperoxides and conjugated dienes formation decreases significantly in VAO and EVO groups compared to baseline values ( P=0.001 and P=0.014 , respectively ) . Vitamin E concentration increases significantly only in VAO group ( P=0.007 ) . Susceptibility of LDL to lipid peroxidation shows a significant increase in lag phase and a significant decrease in maximum diene production in VAO ( P=0.005 ) and EVO groups ( P=0.041 and P=0.005 , respectively ) . CONCLUSIONS Our findings confirm the beneficial effect of EVO on plasma antioxidant status and show for the first time the same effect for VAO supplementation in man . Thus , VAO offers an additional natural food supplement to reduce cardiovascular risk Human plasma platelet-activating factor acetylhydrolase ( PAF-AH ) is a phospholipase A2 that is primarily associated with low density lipoprotein ( LDL ) . PAF-AH activity has also been found in high density lipoprotein ( HDL ) , although it has recently been indicated that there is no PAF-AH protein in HDL . Plasma paraoxonase 1 ( PON1 ) is an HDL-associated esterase , which also exhibits PAF-AH – like activity . The effect of atorvastatin ( 20 mg per day for 4 months ) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA ( n=55 ) or type IIB ( n=21 ) was studied . In both patient groups , atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions ( LDL-4 and LDL-5 ) . Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group . However , because of the reduction in LDL cholesterol levels , the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration . The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin BACKGROUND AND STUDY AIMS The prevalence of non-alcoholic fatty liver disease ( NAFLD ) appears to be increasing . The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 ( PON1 ) activity , lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin . PATIENTS AND METHODS This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex . All of them were subjected to the following investigations : abdominal ultrasonography , serum PON1 activity level , liver function tests , serum lipid profile , fasting and postpr and ial blood glucose and serum levels of malondialdehyde ( MDA ) and glutathione peroxidase ( GP ) .  NAFLD patients were further r and omly classified into two groups ( 25 patients each ) , groups Ia and Ib . Only group Ia received atorvastatin 40 mg tablet for 8months . RESULTS Obesity , dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity ( i.e. , there is a significant increase in lipid peroxidation rate ) in group I compared with group II . After atorvastatin therapy , there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels . CONCLUSION Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis ( NASH ) . Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation , which require follow-up in patients with NAFLD . Atorvastatin may have a role in prevention of , or delay , the transformation of liver steatosis into NASH The purpose of the study was to examine the effects of astaxanthin ( Asx ) on paraoxonase ( PON1 ) activities and oxidative stress status in soccer players . Forty soccer players were r and omly assigned in a double-blind fashion to Asx and placebo ( P ) group .  Blood sample s were obtained before , 45 and 90 days after supplementation .  PON1 activity was assessed by using two substrates : paraoxon and diazoxon . The oxidative stress biomarkers were also examined : total sulphydryl group content ( -SH groups ) , thiobarbituric acid-reactive substances ( TBARS ) , advanced oxidation protein products and redox balance . The significant interaction effect of supplementation and training ( p < 0.05 ) on PON1 activity toward paraoxon was observed . The PON1 activity toward diazoxon increased in Asx group after 90 days ( p < 0.01 ) , while there was no significant difference in P group . SH groups content rose from pre- to post-supplementation period only in Asx group ( supplementation and training , p < 0.05 ; training , p < 0.01 ) . TBARS levels decreased after 45 days and increased after 90 days of regular soccer training in both groups ( training , p < 0.001 ) . Redox balance decreased significantly in response to the regular training , regardless of treatment group ( training , p < 0.001 ) . Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification Background —The hypothesis that paraoxonase ( PON1 ) has a role in preventing atherosclerosis is based on experimental , transgenic , and case-control studies but has not previously been tested prospect ively . Methods and Results —The Caerphilly Prospect i ve Study is a cohort study of men aged 49 to 65 years observed for coronary heart disease ( CHD ) events ( fatal and nonfatal myocardial infa rct ion ) over a mean period of 15 years .  Serum PON1 activity toward paraoxon was measured in 1353 participants .  PON1 activity was 20 % lower in the 163 men who had a coronary event ( P = 0.039 ) . Men in the highest quintile of PON1 activity had a decreased risk compared with those in the lowest quintile ( OR 0.57 [ 95 % CI , 0.33 to 0.96 ] ) . The inverse relationship between quintiles of serum PON1 activity and CHD risk was grade d , the median change in OR across each quintile being 0.87 ( 0.77 to 0.98 ) . After adjustment for all other CHD risk factors , including HDL cholesterol , this median value became 0.90 ( 0.78 to 1.02 ) . PON1 was most predictive of a new CHD event in patients at highest risk by virtue of preexisting CHD ( adjusted median OR for each quintile , 0.74 [ 0.59 to 0.93 ] ; n=313 ) or the presence of other risk factors . For the highest tertile of CHD risk ( n=390 ) calculated by the Framingham equation , adjusted median OR for each quintile was 0.84 ( 0.66 to 1.05 ) ; n=390 . Conclusions —Low serum PON1 activity toward paraoxon is an independent risk factor for coronary events in men at high risk because of preexisting disease or other CHD risk factors
RESULTS Meta- analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities , but not PON1 protein concentration .
The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose , treatment duration and changes in plasma low-density lipoprotein cholesterol concentration .
CONCLUSION The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes
BACKGROUND Decreased activity of the enzyme paraoxonase-1 ( PON1 ) has been demonstrated in cardiovascular diseases .
Statins , the forefront of pharmacotherapy for dyslipidemia , have been shown to enhance PON1 activity but clinical findings have not been conclusive .
OBJECTIVE To systematic ally review the clinical findings on the impact of statin therapy on PON1 status ( protein concentrations and activities of paraoxonase and arylesterase ) and calculate an effect size for the mentioned effects through meta- analysis of available data .