Paraoxonase 1 Arylesterase Activity Research Articles

Association of cadmium, lead and mercury with paraoxonase 1 activity in women.

BackgroundThe activity of paraoxonase 1 (PON1), an antioxidant enzyme whose polymorphisms have been associated with cancer risk, may be associated with metals exposure.ObjectiveTo evaluate PON1 activity in relation to cadmium, lead, and mercury levels in healthy, premenopausal women.MethodsWomen from upstate New York were followed for ≥ two menstrual cycles. Repeated measures linear mixed models estimated the association between cadmium, lead, and mercury levels (by tertile: T1, T2, T3) and PON1 arylesterase (PON1A) and PON1 paraoxonase (PON1P) activity, separately. Analyses were stratified by PON1 Q192R phenotype and un-stratified.ResultsMedian blood cadmium, lead, and mercury concentrations were 0.30 µg/L, 0.87 µg/dL, and 1.15 µg/L. In un-stratified analyses cadmium and mercury were associated with decreased PON1A activity (T2 vs. T1; not T3 vs. T1) but metals were not associated with PON1P. Phenotypes were distributed between QQ (n = 99), QR (n = 117), and RR (n = 34). Cadmium was associated with decreased PON1A activity for QR and RR phenotypes comparing T2 vs. T1 (−14.4% 95% confidence interval [CI] [−20.1, −8.4] and −27.9% [−39.5, −14.0],). Lead was associated with decreased PON1A (RR phenotype, T3 vs. T1 −18.9% [−32.5, −2.5]; T2 vs. T1 −19.6% [−32.4, −4.4]). Cadmium was associated with lower PON1P comparing T2 vs. T1 for the RR (−34.9% [−51.5, −12.5]) and QR phenotypes (−9.5% [−18.1, 0.0]) but not comparing T3 vs. T1. Cadmium was associated with increases in PON1P levels (QQ phenotype, T3 vs. T1 24.5% [7.0, 44.9]) and mercury was associated with increased PON1A levels (QQ phenotype, T3 vs. T1 6.2% [0.2, 12.6]). Mercury was associated with decreased PON1P (RR phenotype, T2 vs. T1 −22.8 [−37.8, −4.1]).ConclusionBlood metals were associated with PON1 activity and these effects varied by phenotype. However, there was not a linear dose-response and these findings await replication.

Paraoxonase1 activity, its Q192R polymorphism and diabetic retinopathy in type 2 diabetes mellitus.

Background: The goal of this study was to investigate the role of paraoxonase1 (PON1) status i.e. activity and Q192R polymorphism, in the development of diabetic retinopathy (DR) in patients of type 2 diabetes mellitus. Methods: This cross-sectional study included 55 normotensive type 2 diabetic patients (duration more than 5 years) admitted in the hospital divided into two groups (with and without DR) on the basis of fundus examination by direct ophthalmoscopy. Serum samples of all patients were subjected for PON1 activity with and without salt using paraoxon as substrate and arylesterase activity of PON1 using phenylacetate as substrate. PON1 phenotyping is carried out using ratio of salt stimulated PON1 activity to arylesterase activity. Results: Arylesterase activity of PON1 was found significantly lower in diabetics with DR than diabetic patients without DR (P = 0.01). Multivariate testing also showed its independent protective association in the development of DR (OR 0.958, [95% CI (0.915-1.004)], P value = 0.023). Moreover, DR was associated significantly in diabetic patients with PON1 R allele carriers (71.05%) than diabetic patients with PON1 QQ homozygotes (29.41%). PON1 R carriers had higher Odds ratio (OR) for DR in univariate analysis (OR 5.891, [95% CI (1.676-20.705)], P value = 0.006) and in multivariate analysis (OR 14.12 [95% CI (0.926-215.2)], P = 0.057) after adjustment of conventional risk factors of diabetes. Also diabetics with homozygous PON1 RR were associated significantly with severe forms of DR. Conclusions: Arylesterase activity of PON1 may be more important in the risk of retinopathy in diabetic individual than the paraoxon hydrolytic activity. Moreover PON1 R allele is associated with susceptibility to DR showing a graded risk relationship to the number of R alleles. Thus the determination of PON1 status may be useful in the risk assessment and management of DR. Key

Paraoxonase 1 lactonase activity and distribution in the HDL subclasses in the cord blood

ObjectivesParaoxonase 1 (PON1) is a lactonase with important antioxidant and immunoprotective properties. We hypothesized that PON1 lactonase activity, PON1, and high-density lipoprotein (HDL) subclasses distribution are different in neonates than in adults.Material and methodsWe studied 83 healthy term neonates (34 males and 49 females) who were born by spontaneous, uncomplicated vaginal delivery. The study also included 17 paired maternal blood samples as well as 20 non-pregnant women collected for comparison. Total and free PON1 lactonase and arylesterase activity, HDL subclasses, PON1, and apolipoprotein distribution in the subclasses were assayed.ResultsPON1 arylesterase activity in the cord blood represented 37% ± 4 of the maternal activity, whereas the PON1 lactonase activity amounted to only 23% ± 5 of the maternal activity. The free arylesterase and lactonase activities were higher in the cord blood by 16 and 36%, respectively. There is a 65% lower HDL2b PON1 in the cord blood than in the maternal serum. When the Lipoprint HDL subclasses were assayed, the neonates showed a larger content (52% higher) of very large HDL as well as a characteristic peak in the middle-sized HDL5 which is unremarkable in the mothers.ConclusionThe novel findings of this study are that the neonates have lower PON1 lactonase activity, higher free PON1, different distributions of PON1 in the HDL subclasses as compared with their mother and adults as well as a distinctive HDL subclass lipid profile. Our data also suggest that the neonate HDL is enriched with an intermediate-sized (and/or less charged HDL) that is also rich in active PON1.

Measurement of serum paraoxonase activity and MDA concentrations in patients suffering with oral squamous cell carcinoma

BackgroundOxidative stress is associated with many diseases including cancer. Oral squamous cell carcinoma (OSCC) is a prevalent cancer involving oral cavity. We evaluate the activity of paraoxonase 1 (PON1) in serum samples of subjects suffering from OSCC along with malondialdehyde (MDA) levels, a marker for oxidative stress. Antioxidant status in OSCC may reflect the role of oxidative imbalance in the disease. MethodsForty-five patients suffering with OSCC and 30 healthy controls were selected for the study. Serum paraoxonase (PON) and arylesterase (ARE) activities were measured in subjects suffering from OSCC and their healthy counterparts. To examine the status of lipid peroxidation, MDA concentrations were estimated and a correlation was determined between PON activities and MDA concentrations. MDA expression in cancer and normal adjacent tissue was studied through immunohistochemical (IHC) analysis. Total reactive oxygen species (ROS) level was determined in serum from normal and diseased subjects. Our results revealed that both PON and ARE activities of PON1 were significantly decreased in OSCC patients. Serum MDA concentrations were inversely correlated to PON activity. Immunohistochemical analysis showed a higher expression of MDA in cancerous tissue. Total ROS levels were found to be significantly elevated in cancer subjects. ConclusionsAlong with other antioxidants, PON levels may act as an indicator of oxidative stress in cancer.

Low paraoxonase 1 arylesterase activity and high von Willebrand factor levels are associated with severe coronary atherosclerosis in patients with non-diabetic stable coronary artery disease.

BackgroundParaoxonase 1 (PON1) activity and von Willebrand factor (VWF) release are associated with lesion initiation in atherosclerosis. Diabetes can complicate coronary artery disease (CAD) due to the production of advanced glycation end products. This study evaluated PON1 activity and VWF levels in non-post-acute coronary syndrome, stable CAD (SCAD) patients without diabetes.Material/MethodsNon-diabetic SCAD patients and patients experiencing acute stress periods were selected (n=130). Forty-seven cases with normal coronary angiography and 50 healthy individuals served as controls. The non-diabetic SCAD group was then stratified into single-vessel lesions, multiple-vessel lesions, and mild or severe luminal stenosis according to the number and the degree of luminal stenoses. Serum PON1 paraoxonase and arylesterase activities, and plasma VWF levels were measured, as well as serum total cholesterol, total triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A1. PON1 arylesterase activity was detected with an ordinary chemistry system using a novel phenylacetate derivative.ResultsBoth PON1 paraoxonase and arylesterase were lower in the non-diabetic SCAD group, but VWF levels were higher (versus controls, all P<0.001). PON1 paraoxonase activity (OR=0.991), PON1 arylesterase activity (OR=0.981), and VWF (OR 2.854) influenced SCAD in multiple logistic regression. Decreased PON1 arylesterase activity and increased VWF levels were associated with severe atherosclerosis in non-diabetic SCAD patients. We also observed a slight negative correlation between VWF and PON1 paraoxonase/arylesterase.ConclusionsPON1 and VWF are detectable markers that may predict the severity of stenoses, ideally facilitating a non-diabetic SCAD diagnosis before the sudden onset of life-threatening symptoms.

Quantification of the arylesterase activity of paraoxonase-1 in human blood

Paraoxonase-1 (PON1) is known as a free-radical scavenging system associated with circulating serum high-density lipoprotein (HDL). PON1 catalyzes the hydrolysis of multiple compounds such as arylesters, lactones and hydroperoxides. The arylesterase (AREase) activity of PON1 is involved in the detoxification of lipid peroxides, which are related to several clinical conditions. Therefore, the possibility of measuring the AREase activity in routine clinical studies would be advantageous. The AREase activity was obtained by monitoring the formation of acetic acid, upon the hydrolysis of phenyl acetate, using 10 μL of sample. The method accuracy was higher than 90% and intra-assay and inter-assay precisions were 96% and 95%, respectively. The method validation supported that this analytical procedure is suitable for use in human serum and heparinized plasma samples, while ethylenediaminetetra-acetic acid (EDTA)-containing samples should be avoided. The methodology herein described constitutes an easy, fast and reliable method for assessing the AREase activity of PON1. This method can be easily implemented as a clinical analytical tool and is also suitable for research purposes.

PON1 status evaluation in patients with chronic arterial occlusion of lower limbs due to atherosclerosis obliterans.

IntroductionHuman paraoxonase (PON1) is a calcium-dependent enzyme physically associated with HDL, and it is believed to contribute to the atheroprotective effect of HDL. The aim of the study was to evaluate PON1 status in patients with atherosclerosis obliterans as an effect of ischemia regarding its activity and phenotype distribution.Material and methodsThe study group consisted of patients with chronic arterial occlusion of the lower limbs due to atherosclerosis obliterans (AO). The patients were divided into two groups according to the degree of ischemia: moderate (MI), and critical (CI). The ratio of the hydrolysis of salt-stimulated PON1 activity to the hydrolysis of phenylacetate was used to assign individuals to one of three possible phenotypes (low activity – A, medium activity – AB, high activity – B). It was observed that PON1 arylesterase activity was affected by ischemia of the lower limbs depending on its degree.ResultsThe odds ratio and the relative risk analysis showed that the patients with moderate ischemia are much more often characterized by phenotype A than by phenotype B. The low activity phenotype A occurs over twice as often in patients with chronic ischemia of the lower limbs as in individuals from the control group (OR = 2.125; 1.96 to 3.776, p = 0.0143).ConclusionsThis study presents the low activity phenotype A in relation to the risk of ischemia of the lower limbs due to atherosclerosis and shows the potentially important role of PON1 in conclusion of the process leading to intensification of ischemia degree.

Harbingers of Neonatal Birth Weight: The PON1 Arylesterase and Lactonase Activities

Objective: An important predictor for infant survival is birth weight. Normal fetal growth is related to various intrauterine factors. Low birth weight is thought to have relation with oxidative stress which plays an important role in reducing the birth weight. Among the paraoxonase family PON1 protects LDL and HDL from the lipid peroxidation. This is HDL associated enzyme having antioxidant property. We aimed to evaluate the arylesterase and lactonase activity of PON1 in cord blood in relation to birth weight. We hypothesized that cord blood PON1 arylesterase and lactonase activities will be compromised in neonates having low birth weight. Methods: We included 80 neonates born in our hospital irrespective of mode of delivery as 40 cases and 40 controls. PON1 arylesterase and lactonase activity were measured using spectrophotometer. Results: Serum arylesterase activity decreased significantly in low birth weight babies (p<0.05). Linear regression analysis (R=0.595) indicates significant correlation between arylesterase and birth weight. Serum lactonase activity of PON1 also gets reduced in low birth weight babies. Its linear regression analysis showed (R=0.716) suggesting significant correlation between lactonase and birth weight. Conclusion: Reduced PON1 activity can be explained on the basis of ER stress and atherogenic changes in the placental circulation. Ours is the first study in cord blood paraoxonase activities in relation to birth weight. As the sample in our study is cord blood, it is essentially a noninvasive one. Further studies are needed in this direction to assess the effect of the oxidative stress on fetus through cord blood in its long term prospective.

Age-dependent paraoxonase 1 (PON1) activity and LDL oxidation in Wistar rats during their entire lifespan.

Paraoxonase 1 (PON1) is an HDL bound enzyme which plays a key role in the protection of LDL and HDL from oxidation by hydrolyzing activated phospholipids and lipid peroxide products. Oxidative stress plays a crucial role in the development of atherosclerosis by oxidation of LDL. This study was conducted to determine age-dependent changes in plasma PON1 arylesterase activity and LDL oxidation in rats during their entire lifespan. 48 Wistar strain rats were grouped in six different age groups (1, 4, 8, 12, 18, and 24 months). We observe a significant (P < 0.001) age-dependent decrease in plasma PON1 arylesterase activity correlating with increase in susceptibility of LDL oxidation and increase in plasma MDA level concomitantly with a significant (P < 0.001) decrease in plasma radical scavenging activity after 8 months. The reduction of PON1 and free radical scavenging activity with age could have a considerable impact on the increased incidence of atherosclerosis with age. Our observation of a significant decline in PON1 activity which correlates with increased LDL oxidation after 8 months of age is an interesting observation and needs further investigation.

Activation of paraoxonase 1 after hemodialysis is associated with HDL remodeling and its increase in the HDL2 fraction and VLDL

BackgroundParaoxonase 1 (PON1) activity is lower in renal failure patients. We hypothesize that part of the salutatory effect of hemodialysis on PON1 activity that we have previously found is due to HDL remodeling and shift of PON1 among HDL particles. MethodsA total of 42 patients (18 females and 24 males, 63±12yr) on long-term HD, with a mean dialysis course of 6.4yr (range 1–19yr), were recruited. PON1 arylesterase and lactonase activities, PON1 and apolipoprotein distribution in HDL subclasses were measured by gel gradient electrophoresis and western blotting. ResultsThe 3 different activities of PON1 we measured were significantly lower in patients as compared to control subjects; lactonase by 11%, triesterase by 19% and arylesterase by 20%, p<0.01. HDL increased slightly by 4.6%. LDL increased by 13% and VLDL decreased by 30%. These data are compatible with enhanced lipolysis of VLDL that is transformed into LDL. VLDL-PON1 activity increases significantly by 60%. PON1 activity increases by 16% in HDL2whereas by this approach we could determine a 10% increase in the total area under the curve corresponding to total HDL. Changes in total lactonase activity were associated with changes in VLDL-PON1 and HDL2. In parallel with PON1 activation and shifts among particles, there are significant changes in apoE which increases notably in HDL2, paralleling the changes in PON1. No significant changes in apoAI or apoA-II the main structural HDL apolipoproteins were apparent after dialysis. ConclusionsHD produces an activation of PON1 that can be predicted in part (30%) by efficiency of dialysis and in part (25%) by PON1 shifts to HDL2or VLDL (p<0.01). The removal of inhibitors and the change in the environment of PON1 in the micro-heterogeneity of HDL subclasses optimizes PON1 activity.

Plasma paraoxonase 1 arylesterase activity in d-galactose-induced aged rat model: correlation with LDL oxidation and redox status

There is much evidence linking the involvement of oxidative stress in the pathogenesis of aging. Paraoxonase 1 (PON1) is an HDL-associated antioxidant enzyme that inhibits the oxidative modification of low-density lipoproteins (LDL). We have investigated the changes in plasma PON1 activity, LDL oxidation, radical scavenging activity and lipid peroxidation in D-galactose-induced aging rat model and also compared the results with 24-month naturally aged rats. Arylesterase activity of PON1, susceptibility of LDL for oxidation, plasma radical scavenging activity and plasma thiobarbituric acid reactive substances (TBARS) were measured in normal control rats (4-months-old control rats subjected to D-galactose-induced experimental aging, and 24-month-old naturally aged rats). There was a significant decrease in plasma PON1 arylesterase activity in both subcutaneous D-galactose-treated groups and 24-month-old aged rats (P < 0.05, for each). TBARS, an oxidative stress marker, was seen to increase in the experimental groups (P < 0.01). In both subcutaneous galactose-treated and naturally aged rats, there was a significant rise in plasma LDL oxidation (P < 0.05, for each). However, radical scavenging activity was decreased significantly (P < 0.01) in both groups, as compared to control. The D-galactose-induced rat model of aging mimics the naturally aged rat with reference to PON1 arylesterase activity and susceptibility to LDL oxidation. The results emphasize the importance of PON1 with respect to aging and its association with redox balance of the body.

Correlation of Paraoxonase1 Activities with Birth Weight

To evaluate arylesterase and lactonase activity of paraoxonase (PON)1 in cord blood of neonates in relation to their birth weight. The authors hypothesized that cord blood PON1 arylesterase and lactonase activities will be compromised in neonates having low birth weight. Eighty neonates born in authors' hospital, irrespective of mode of delivery were included. Forty children with low birth weight were included in case group and 40 with normal birth weight were included as controls. PON1 arylesterase and lactonase activities were measured. Serum arylesterase activity decreased significantly in low birth weight babies (p < 0.05). Linear regression analysis (R = 0.728) indicated significant correlation between arylesterase and birth weight. Serum lactonase activity was also reduced in low birth weight babies. Its linear regression analysis (R = 0.727) indicated significant correlation between lactonase and birth weight. PON 1 activity is significantly reduced among low birth weight babies in comparison to normal weight babies.

Paraoxonase 1 and oxidative stress in paediatric non‐alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) in children is a significant public health concern. Oxidative stress is an important component in the pathophysiology of NASH. Several enzymatic antioxidant mechanisms protect the liver from oxidative injury. Examination of the expression of these enzymes in NASH livers may provide insight on the roles for these antioxidant mechanisms in the pathophysiology of NASH. The mRNA expression of catalase, glutathione peroxidase 1 (GPX1), glutathione reductase (GSR), paraoxonase 1 (PON1) and other reactive oxygen species-related genes was evaluated by microarray and quantitative real-time PCR analyses. The PON1 protein levels were evaluated in liver and serum by Western blot analyses. Serum enzymatic activities of GPX, GSR and PON1 (paraoxonase and arylesterase activities) were examined. NASH livers exhibited elevated mRNA expression of catalase and PON1, but not GPX1 or GSR. No difference in serum GPX or GSR activity was detected between NASH patients and controls. Elevated expression of PON1 mRNA and protein was detected in NASH livers, but serum PON1 protein and activities were not elevated. Elevated expression of catalase and PON1 suggests protective roles for these antioxidants in NASH livers. Given the importance of oxidative stress in the pathophysiology of NASH, future studies focusing on these enzymes could identify important targets for therapeutic or preventive interventions for NASH patients.

An Acridinium Ester for Determination of Serum Arylesterase Activity in Patients with Coronary Heart Disease

Paraoxonase (PON) is a hydrolyase correlated with many chronic diseases. The use of 9-(4-chlorophenyloxycarbonyl)-10-methylacridinium triflate ester (CPOCMA) as a substrate for determination of serum arylesterase PON activity had been reported. It is meaningful to compare this substrate with phenyl acetate further with serum samples of patients with coronary heart disease (CHD, n=104). Correlations of PON arylesterase activity with CHD and also with age were analyzed. There was no significant difference in serum arylesterase activity (based on the CPOCMA or the phenyl acetate) between of the CHD inpatients and controls at same age level (45-60 years old). Statistically negative correlation of serum PON CPOCMAase activity (p=0.020) but not the activity based on phenyl acetate (p&gt;0.05) with age was observed. Based on the both substrates, significant decrease in PON activity was found in the old CHD inpatients (≥60 years old), compared with that in the young CHD inpatients (&lt;60 years old), or with that in the young controls. The methods based on CPOCMA substrate and based on the phenyl acetate demonstrated consistent results in correlation with CHD, but different results in correlation of PON activity with age.

Serum paraoxonase-1 as biomarker for improved diagnosis of fatty liver in dairy cows

BackgroundFatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows.ResultsA comparative cohort study using serum specimens from Holstein–Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (P<0.001) in cows suffering from fatty liver. The area under the receiver operating characteristic curve (AUC-ROC) of PON1 activity for diagnosis of fatty liver was 0.973–0.989 [95% confidence interval (CI) 0.941, 1.000] which was higher than the AUC-ROC of aspartate aminotransferase (AST), lecithin-cholesterol acyltransferase (LCAT), alkaline phosphatase (ALP), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). We found that adding serum PON1 measurement to different batteries of serum diagnostic panels showed a combination of high sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver.ConclusionsThe present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.

Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL

HDL-associated paraoxonase 1 (PON1) activity is associated with cardiovascular and other human diseases. As the role of genetic variants outside of the PON gene cluster on PON1 activity is unknown, we sought to identify common and rare variants in such loci. We typed 33,057 variants on the CVD chip in 1,362 subjects to test for their effects on adjusted-PON1 activity. Three novel genes (FTO, ITGAL, and SERPINA12) and the PON gene cluster had SNPs associated with PON1 arylesterase (AREase) activity. These loci were carried forward for rare-variant analysis using Exome chip genotypes in an overlapping subset of 1,051 subjects using sequence kernel association testing. PON1 (P = 2.24 × 10(-4)), PON3 (P = 0.022), FTO (P = 0.019), and SERPINA12 (P = 0.039) had both common and rare variants associated with PON1 AREase. ITGAL variants were associated with PON1 activity when using weighted sequence kernel association testing (SKAT) analysis (P = 2.63 × 10(-3)). When adjusting for the initial common variants, SERPINA12 became marginally significant (P = 0.09), whereas all other findings remained significant (P < 0.05), suggesting independent rare-variant effects. We present novel findings that common and rare variants in FTO, SERPINA12, and ITGAL predict PON1 activity. These results further link PON1 to diabetes and inflammation and may inform the role of HDL in human disease.

Plasma Protein Hydroperoxides During Aging in Humans: Correlation with Paraoxonase 1 (PON1) Arylesterase Activity and Plasma Total Thiols

Oxidative stress is thought to play a major role in the development of several age-dependent diseases. Proteins are major targets for oxidative attack. Protein hydroperoxides are formed by hydroxyl and singlet oxygen attack on protein, forming relatively stable hydroperoxides on histidine, tyrosine and tryptophan residues. This study investigated the levels of plasma protein hydroperoxides and antioxidant potential of plasma during aging in humans. We correlated the protein hydroperoxide formation with plasma antioxidant potential, paraoxonase 1 (PON1) arylesterase activity and plasma total thiols. The protein hydroperoxides and antioxidant potential were measured in plasma of human subjects aged between 20 and 81 years of both genders. Increase in plasma protein hydroperoxides and decrease in plasma antioxidant potential were observed as function of human age. This study provides strong correlation between plasma protein hydroperoxides formation and decrease in plasma antioxidant potential during aging. PON1 arylesterase activity and plasma total thiols levels were also found to show significant correlation with increasing levels of plasma protein hydroperoxides during aging. The plasma protein hydroperoxides provide a reliable marker of long-term redox balance and degree of oxidative stress during aging process.

Original article Paraoxonase 1 (PON1) gene -108C&gt;T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia

Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia--136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.

Distribution of Paraoxonase 1 polymorphisms and activities in obese patients

Study objective. The objective of this study was to investigate PON1 phenotype and genotype in Romanian patients with abdominal obesity. Materials and methods. The study groups consisted of 88 patients with abdominal obesity and 46 subjects with normal waist circumference, matched for age and gender. For each patient, we determined the clinical parameters that may influence PON1 activities. Q192R and L55M polymorphisms analysis in the PON1 gene were performed by PCR-RFLP using specific primers and restriction enzymes. PON1 lactonase, paraoxonase and arylesterase activities were assayed by spectrophotometric methods. Analysis of PON1 genotypes and activities distribution in the obese and non-obese individuals was performed with MedCalc Software (Version 12.4.0.0). Results. There was no statistically significant difference between obese and controls in regards to age and gender. The study revealed that PON1 activities were not influenced by gender. Of all PON1 activities, only the paraoxonase activity was inversely correlated with age, being significantly reduced in patients with abdominal obesity compared to non-obesity (p=0.009). Abdominal circumference independently influenced only the variation of arylesterase activity (R=6.5%, p=0.003). Distribution of PON1 genotypes in the study groups was significantly different (p=0.007) only for the Q192R but not for the L55M genotypes. The QR Corresponding author: Stefan Cristian Vesa, Department of Pharmacology, Toxicology and Clinical Pharmacology, ”Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 6 Pasteur Street, 400349, Cluj-Napoca, Cluj, Romania Telephone: +40740125980, Fax: +40264595629, Email: stefanvesa@gmail.com 381 DOI: 10.2478/rrlm-2013-0037 Research article Unauthenticated Download Date | 7/15/16 6:10 AM Revista Româna de Medicina de Laborator Vol. 21, Nr. 4/4, Decembrie 2013 genotype had the highest influence on paraoxonase activity (R=40.6; p<0.001). The MM genotype had the greatest influence on arylesterase (R=11.3%, p<0.001) and lactonase activities (R=7.4%, p<0.001). Conclusions. Q192R genotypes distribution was significantly different in obese patients and the QR genotype influenced greatly the paraoxonase activity. The MM genotype had the most important independent influence on the lactonase and arylesterase activities.

Relationship of serum paraoxonase enzyme activity and thermal burn injury.

This study investigated changes in serum oxidative stress parameters in burn cases compared to healthy controls. This study was performed in 41 burn patients with mild to severe thermal burn injuries and 38 healthy volunteers. The burn cases were selected from patients who were hospitalized in the burn unit for the treatment of second- and third-degree burns. Malondialdehyde (MDA) levels and PON-1 paraoxonase and arylesterase activities were measured in patient serum samples. PON-1 paraoxonase activity and MDA levels in patients with major thermal burn injury were significantly higher than healthy controls, but PON-1 arylesterase activities were lower. A significant negative correlation was observed between the burn percentage of the total body surface area and the PON-1 arylesterase activities in patients. Human thermal burn injury was associated with an increase in MDA production and a decrease in PON-1 arylesterase activity, which was proportional to the percentage of total burned surface area.