Decreased Paraoxonase-1 Activity Research Articles

Glyphosate Suppresses the Ability of PON1 to Hydrolyse Oxidized-LDL in the Exposed Farm Workers in Pahang, Malaysia

INTRODUCTION: Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which is known to hydrolyse most pesticides including organophosphates (OPs) and prevent atherosclerosis by inhibiting oxidative modification of low-density lipoprotein (LDL). Glyphosate is one of the common organophosphate pesticides used in agriculture in many developing countries including Malaysia. The aim of this study to is to assess the PON1 ability to hydrolyse oxidized LDL in glyphosate exposed farm workers. MATERIALS AND METHODS: In this cross-sectional comparative study, a total of 103 subjects (53 Glyphosate-exposed and 50 non-exposed) were recruited. Fasting serum samples were analysed for PON1 activities towards substrates paraoxon, phenylacetate, and diazoxon, as well as for lipid profiles and oxidized-LDL (ox-LDL). RESULTS: The results showed lower basal paraoxonase activity [156.96 (58.87) vs 177.06 (66.78)], arylesterase activity [90.06 (17.14) vs 96.92 (23.87)] and diazoxonase activity [850.93 (206.75) vs 990.48 (248.73)] in glyphosate-exposed compared to non-exposed, however, only diazoxonase activity was statistically significant (p<0.05). PON1 activity is not significantly different with different length of period of exposure except for arylesterase. There was also significantly higher (p<0.05) ox-LDL in the exposed group but no significant differences in lipid profiles (p>0.05) between the two groups. The PON1 to ox-LDL ratio which probably reflects the ability of PON1 to hydrolyse ox-LDL were also significantly lower (p<0.05) among the glyphosate-exposed group. CONCLUSION: The results suggested that the decreased PON1 activity in glyphosate-exposed individuals could predispose them to the development of atherosclerosis and coronary artery disease through decreased PON1 ability to hydrolyse ox-LDL.

Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine-class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity.

Paraoxonase 1 (PON1) was purified 148.80-fold in 37.92% yield by hydrophobic interaction chromatography technique. The purity of PON1 was checked by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with a single band of 43kDa. The in vitro effects of nine different calcium channel blockers on PON1 activity were evaluated. All drugs strongly decreased PON1 activity, and IC50 levels were between 13.987 ± 0.59 and 238.104 ± 2.14μM, Ki values between 8.58±0.36 and 111±1.27μM. The drugs with the strongest inhibitory effect were nisoldipine with 13.987 ± 0.59μM and nicardipine with 20.158 ± 0.43μM. The mechanism of action for the inhibition of the enzyme by nisoldipine and nicardipine was investigated through molecular docking. The stability of enzyme-ligand complexes obtained from the docking was explored through molecular dynamics simulation. The binding affinity of the ligands toward the enzyme was also investigated through MMPBSA (molecular mechanics Poisson-Boltzmann surface area method). The computational analysis demonstrated these compounds could inhibit the enzyme. Nisoldipine had the strongest binding, and its complex was the most stable one. Furthermore, nicardipine was found to have the highest affinity toward the enzyme.

Cardioprotective Role for Paraoxonase-1 in Chronic Kidney Disease.

Paraoxonase-1 (PON-1) is a hydrolytic enzyme associated with HDL, contributing to its anti-inflammatory, antioxidant, and anti-atherogenic properties. Deficiencies in PON-1 activity result in oxidative stress and detrimental clinical outcomes in the context of chronic kidney disease (CKD). However, it is unclear if a decrease in PON-1 activity is mechanistically linked to adverse cardiovascular events in CKD. We investigated the hypothesis that PON-1 is cardioprotective in a Dahl salt-sensitive model of hypertensive renal disease. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS-WT rats) and mutant PON-1 rats (SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated using CRISPR gene editing technology. Age-matched 10-week-old SS and SS-PON-1 KO male rats were maintained on high-salt diets (8% NaCl) for five weeks to induce hypertensive renal disease. Echocardiography showed that SS-PON-1 KO rats but not SS-WT rats developed compensated left ventricular hypertrophy after only 4 weeks on the high-salt diet. RT-PCR analysis demonstrated a significant increase in the expression of genes linked to cardiac hypertrophy, inflammation, and fibrosis, as well as a significant decrease in genes essential to left ventricular function in SS-PON-1 KO rats compared to SS-WT rats. A histological examination also revealed a significant increase in cardiac fibrosis and immune cell infiltration in SS-PON-1 KO rats, consistent with their cardiac hypertrophy phenotype. Our data suggest that a loss of PON-1 in the salt-sensitive hypertensive model of CKD leads to increased cardiac inflammation and fibrosis as well as a molecular and functional cardiac phenotype consistent with compensated left ventricular hypertrophy.

The effect of homocysteine thiolactone on paraoxonase and aryl esterase activity of human serum purified paraoxonase 1 in vitro experiments.

The important role of lipoproteins, particularly low-density lipoprotein (LDL) and high-density lipoprotein (HDL), has been highly regarded among the known causes of cardiovascular disease (CVD). A wide range of risk factors may cause structural and functional changes in lipoprotein particles, resulting in deposition and formation of atherosclerotic plaques. Homocysteine is one of the most important risk factors in heart disease, and its atherosclerotic properties appear to be related to its intermediate metabolite called homocysteine thiolactone (HCTL). The major aim of the present investigation was to study the effect of HCTL in different concentrations (10, 50, and 100 μM) on paraoxonase and aryl esterase activities of purified human serum paraoxonase 1 (PON1) antioxidant enzyme related to HDL, as an extracellular hydrolyzing enzyme of HCTL. In order to purify PON1 enzyme from human serum, three-step chromatographic methods including DEAE Sephadex A50, Sephadex G100, and DEAE Sephadex A50 were used. Protein concentration and paraoxonase and aryl esterase activities of each fraction were measured separately and the highest activities fractions were collected and subsequently pooled together for the next steps. Ultimately, both activities of PON1 in the presence of different concentrations of HCTL were measured in triplicate by spectrophotometry technique. HCTL at concentrations of 50 and 100 μM decreased both paraoxonase and aryl esterase activities (P < 0.05) in comparison with the control group, which is directly related to the increase in HCTL concentration. However, at a concentration of 10 μM HCTL, no significant difference was observed in both paraoxonase and aryl esterase activities compared to the control group. HCTL is a highly toxic and reactive compound that is produced in all cells. Extracellular enzyme PON1 causes its hydrolysis with high efficiency. The results obtained from the present study showed that paraoxonase and aryl esterase activities decreased in vitro in the presence of HCTL and therefore, HCTL may cause changing in the protein structure of this enzyme. Previous in vivo studies have also shown decrease of PON1 activity in patients with hyperhomocysteinemia.

Serum Paraoxonase-1 Activity and the Risk of Prostate Cancer Recurrence in Patients Treated with Radiotherapy.

The antioxidant paraoxonase-1 (PON1) may be involved in the response to radiation-induced oxidative stress and possibly prevent cell apoptosis. The correlation of PON1 with the risk of cancer recurrence after radiotherapy (RT) is not yet explored. We investigated changes in the activity of PON1 in patients with prostate cancer (PCa) undergoing RT, and the relation of PON1 activity to the risk of recurrence after RT. We included 56 men with PCa. Blood samples were obtained before irradiation and after the completion of RT. Patients were followed for an average of 51.2 months. Each case of biochemical recurrence was confirmed with biopsy. The control group was composed of 60 healthy men. There was no significant difference in PON1 activity between the control group and patients pre-radiotherapy. Irradiation was associated with a significant decrease in PON1 activity. Patients with PCa recurrence had significantly higher serum PON1 activity than those recurrence-free, both before and after RT. PON1 activity was a predictor of PCa recurrence, with sensitivity over 80% and specificity over 64%. Our results suggest that PON1 activity may be a predictor of PCa recurrence risk after RT. Studies with a larger number of patients and longer follow-up are needed to confirm this hypothesis.

Asendan aort dilatasyonunda oksidatif stres ile ilişkili belirteçlerin rolü: malondialdehit ve paraoksonaz-1 aktivitesi

Aim: This study aimed to evaluate the antioxidative and oxidative status of patients with ascending aortic dilatation using malondialdehyde, an oxidative stress marker, and paraoxonase-1 activity, an antioxidant enzyme.Methods: This cross-sectional study was conducted between August and December 2020. It included 56 consecutive patients (mean age 55.3 ± 8.6 years; range 31 to 67 years; 26 males, 30 females) with ascending aortic dilatation and 33 sex-and age-matched controls (mean age 54.5 ± 10.5 years; range 32 to 67 years; 13 males, 20 females) with normal aortic diameters. All participants were evaluated using transthoracic echocardiography. Malondialdehyde was analyzed using the thiobarbituric acid assay. Paraoxonase-1 activity was measured manually using a spectrophotometer. The relation of ascending aortic dilatation with malondialdehyde levels and paraoxonase-1 activity was identified with correlation analyses.Results: The patient group had significantly higher mean malondialdehyde than the control group (2.5 ± 1.9 μmoL/mL and 1.7 ± 0.3 μmoL/mL, respectively; p &amp;lt; 0.001). The patient group had significantly lower mean activity of paraoxonase-1 than the control group (18.5 ± 12.9 U/mL vs.30 ± 17.6 U/mL, respectively; p &amp;lt; 0.002). Serum malondialdehyde was negatively correlated with ascending aortic diameter (r = 0.293, p = 0.009). A significant negative correlation was found between the activity of serum paraoxonase-1 and ascending aortic diameter (r = -0.364, p = 0.001). Malondialdehyde levels and paraoxonase-1 activity were independent predictors of ascending aortic dilatation.Conclusion: The results are in line with the notion that increased malondialdehyde levels indicate lipid peroxidation, and decreased paraoxonase-1 activity indicates impaired antioxidant defense. Using them may help protect against the pathophysiology of ascending aortic dilatation.

The paraoxonase 1 activity and lipid levels in umbilical cord blood and maternal venous blood, and their relations according to birth weight

Objectives: Aim of this study is to find out the clinical relevance of estimating paraoxonase activity of PON1 enzyme, triglyceride (TG), total cholesterol, HDL, and LDL levels in maternal serum and umbilical cord blood according to birth weight. Methods: Venous blood samples were taken from mothers just before birth. Babies were divided into four groups: normal-weight babies, premature babies, low birth weight babies, and postmature babies. The weight of the newborns was measured and cord blood was taken. The samples were looked at HDL, LDL, total cholesterol, triglyceride levels and PON1 activities. We have investigated the paraoxonase activity of the PON1 enzyme. Enzyme activity assay was obtained spectrophotometrically measurement of p‐nitrophenol at 412 nm. Results: Maternal PON1 paraoxonase activity levels in Pre-Term show a significant decrease in cases as compared to other groups. Baby PON1 paraoxonase activity levels are also found to be significantly decreased in cases concerning the Term and Post-Term groups. There was a significant difference in all values the such as baby's weight, TG, Total cholesterol, HDL, LDL and PON1.belonging to babies (p &amp;lt; 0.05). Conclusions: Decreased paraoxonase activity in maternal serum may be considered as an additional risk factor for the development of low birth weight. It appears that PON1 activity plays an important role in infant development and affects birth weight. We think that the paraoxonase activity of the PON1 enzyme in mothers may be a marker in predicting the babies who are at risk in terms of birth weight.

Role of oxidant-antioxidant enzymes in managing the cardiovascular risks in nephrotic syndrome patients

Increased reactive oxygen species (ROS) in nephrotic syndrome (NS) are involved in the oxidation of membrane proteins, lipoproteins and several receptor molecules ultimately leading to their functional deficit. It is involved in the pathogenesis of dyslipidemia in NS and also increases the oxidation of LDL (oxLDL), which is an important risk factor in thrombus generation and atherosclerosis. Myeloperoxidase (MPO) is an early predictor of myocardial infarction and adverse cardiac events in patients with chest pain. MPO can also foresee the recurrent acute coronary syndrome (ACS) and myocardial infarction in patients. ‘MPO oxidized LDL’ also induces ROS production, lipid accumulation and reduces the antioxidant response in macrophages, however in an augmented way by using different pathways and might be more atherogenic. Paraoxonase 1 (PON1) prevents the oxidative modification of serum lipoproteins, which is one of the crucial steps in the initiation of atherogenesis. PON1 also contributes to the anti-atherogenic effect of HDL-c. Adult NS patients have increased lipid hydroxide levels and significantly decreased PON1 activity and total sulfhydryl levels when compared to healthy controls. While the increased risk of cardiovascular disease in NS patients is well documented, the exact etiology still remains controversial. This prevents the development of a specific treatment modality for the same. MPO as well as PON1 were found as important markers for the management of cardiovascular risk in NS patients. Estimation of these enzymes can therefore be performed in routine clinical practice as prognostic markers, owing to its ease of estimation and cost effectiveness.

Overweight and obesity in polycystic ovary syndrome: association with inflammation, oxidative stress and dyslipidaemia.

Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an antioxidative enzyme located on HDL particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. In 115 PCOS patients, lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products, malondialdehyde (MDA), prooxidant-antioxidant balance (PAB), total antioxidative status (TAS) and superoxide dismutase (SOD) and PON1 activity. Overweight/obese PCOS patients (n 55) had increased OS compared with normal weight patients (n 60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P < 0·05). PAB was in negative correlation with HDL 2a (P < 0·001), whereas MDA and SOD correlated positively with HDL 3 subclasses (P < 0·05). Serum PON1 activity was positively associated with proportions of PON1 activity on HDL 2b (P < 0·05) and 2a (P < 0·01), but negatively with the proportion on HDL 3 particles (P < 0·01). LDL B phenotype patients had increased TAS, SOD and PON1 activity on HDL 2b, but decreased PON1 activity on HDL 3 subclasses. OS is associated with altered lipoprotein subclasses distribution in PCOS patients. Obesity in PCOS affects the profile of HDL subclasses, reflected through the reduced proportion of PON1 activity on HDL 3 subclasses in the presence of sdLDL particles.

The effect of endurance and endurance-strength training on body composition and cardiometabolic markers in abdominally obese women: a randomised trial

Studies comparing the effect of endurance and endurance-strength training on cardiometabolic markers provided inconsistent results. Therefore, the study aimed to compare the effect of endurance and endurance-strength training on body composition and cardiometabolic parameters in abdominally obese women. In this randomised trial, 101 subjects were included and divided into endurance (n = 52) and endurance-strength (n = 49) training. During the 12-week intervention, participants performed supervised one-hour training three times a week. Body composition, blood pressure (BP), markers of glucose and lipid homeostasis, and myoglobin levels were measured before and after the intervention. In total, 85 subjects completed the trial. Both interventions decreased fat mass and visceral adipose tissue and increased free fat mass, appendicular lean mass index and lean mass index. Neither endurance training nor endurance-strength training affected glucose and lipid metabolism. However, only endurance training significantly decreased paraoxonase and myoglobin levels. Both training programmes significantly decreased BP, with a more reduction of diastolic BP noted in the endurance group. In conclusion, both training programmes had a favourable effect on body composition but did not improve glucose and lipid homeostasis. Besides, endurance training decreased paraoxonase activity and myoglobin levels and was more effective in reducing BP.The study was registered with the German Clinical Trials Register (DRKS) within the number: DRKS00019832 (retrospective registration), date of registration: 26/02/2020.

Paraoxonase 1 low activity and SYNTAX score may predict postoperative complications after coronary artery surgery.

Coronary artery bypass grafting (CABG) seems to present a powerful trigger of oxidative stress (OS) and acute inflammatory response. This study aimed to estimate the effects of off-pump coronary artery bypass (OPCAB) grafting on the OS that is commonly observed in patients undergoing operation under cardiopulmonary bypass (CPB). Additionally, we aimed to examine the relationship between and paraoxonase 1 (PON1) activity and the degree of stenosis, severity and complexity of the atherosclerotic lesions, estimated by SYNTAX score (SS). Study group of 107 patients scheduled for CABG were divided into CPB and OPCAB group. Blood samples for OS markers measurement were collected at six-time intervals: before skin incision (t1), immediately after surgery (t2), 6h (t3), 24h (t4), 48h (t5) and 96h after cessation of the operation and surgical trauma (t6). SS was calculated. A significant decrease in lipid hydroperoxides (LOOH) and advanced oxidation protein products (AOPP) levels after both types of surgeries were observed, whereas PON1 reduction was observed higher in the CPB than in the OPCAB group. A significant inverse correlation between SS values and PON1 activity, preoperatively and during the early postoperative hours after surgery [in t2, t3 time intervals (p<0.05 for all)] was found. ROC analysis showed that for CPB patients, Model with all OS parameters showed excellent accuracy (AUC=0.957, p<0.001) for prediction postoperative complications. Decrease in PON1 activity during the early post-operative phases was related to higher SS. This relationship was more convincing in CPB, compared with OPCAB patients. Moreover, integrated models of OS status parameters have the capability to predict the development of postoperative complications.

Comparison of high-fat and high-carbohydrate diets for obtaining an experimental model of metabolic syndrome

Introduction. Metabolic syndrome is a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance and atherogenic dyslipidemia. Given the wide geographical distribution and growing number of people suffering from this disease, there is an urgent need in developing animal models that would accurately reproduce the development of all symptoms of human metabolic syndrome (insulin resistance, dyslipidemia, obesity and hypertension). The most cost-effective method related to the real causes of metabolic syndrome is the use of different types of diets. Materials and Methods. The study was performed on white outbred male rats about 6 months old and weighing 300–400 g. The metabolic syndrome was induced by high-fat and high-carbohydrate diets. The lipid-enriched diet involved the consumption of regular chow diet for laboratory animals with additional fat content (40 % by weight of chow). The source of additional lipids was olive oil, which is rich in monounsaturated fatty acids (MUFAs). Animals on the diet enriched in carbohydrates together with regular chow diet for laboratory animals consumed 10 % fructose solution instead of drinking water. Glucose tolerance tests were conducted and areas under the glycemic curves were calculated. We determined the content of glycated hemoglobin and glucose concent­ration, the concentration of low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides and cholesterol in the blood plasma of rats. Results. The development of metabolic syndrome induced by an excessive consumption of carbohydrates and lipids for 42 days was accompanied by impaired glucose tolerance, increased glycosylated hemoglobin, triglycerides and cholesterol concentrations, as well as a decreased HDL content. An increase in the concentrations of LDL and activity of paraoxonase were found due to the induction of the pathological condition by an excessive fat intake, while a high carbohydrate diet caused a decrease in paraoxonase activity. Conclusions. The use of fructose for 42 days causes the most pronounced manifestations of the studied pathology. The use of this model will allow determining the biochemical and molecular changes that accompany the development of this pathological condition. It will also facilitate the development and evaluation of the effectiveness of new therapeutic approaches to the treatment of metabolic syndrome.

Serial measurements of Paraoxonase-1 (PON-1) activity in horses with experimentally induced endotoxemia

BackgroundParaoxonase-1 (PON-1) is an antioxidant enzyme, whose activity decreases during the acute phase response in many species. Little is known about PON-1 and its role as a negative acute phase protein during septic inflammation in horses, but promising findings about its utility in diagnosing SIRS and predicting the outcome in diseased horses, were recently highlighted. The objective of the study was to investigate the behaviour of PON-1 in horses after experimentally induced endotoxemia. To this aim, PON-1 activity was measured on 66 plasma samples collected from six clinically healthy mares, previously included in another study, before and at multiple time points between 12 and 240 h after intravenous infusion of Escherichia coli O55:B5 lipopolysaccharide (LPS).ResultsCompared with baseline values, a progressive transient decrease of PON-1 activity was observed starting from 24 h post-infusion, with lowest values observed between 3 to 7 days post-infusion, followed by a normalisation to pre-infusion levels the tenth day.ConclusionsThe results of this study suggest that measurement and monitoring of PON-1 activity might be useful to evaluate progression and recovery from endotoxemia in horses. Further studies in horses with naturally occurring sepsis are warranted.

Association between serum paraoxonase 1 activity and its polymorphisms with multiple sclerosis: a systematic review.

Human serum paraoxonase (PON) is an enzyme that is synthesized by the liver and enters the bloodstream, and it is transmitted by high-density lipoproteins (HDL). Paraoxonase 1 (PON1) is a hydrolytic enzyme with a wide range of substrates and the ability to protect against lipid oxidation. In this study, due to the activity of PON1 in the brain and its antioxidant effects on the reduction of neurological disorders in the central nervous system, the role of PON1 and its polymorphisms related to multiple sclerosis has been examined to enhance treatment methods. This article is a systematic review. In this study, the role of PON1 and its polymorphisms in multiple sclerosis (MS) has been investigated. Articles published in Persian and international databases of SID, Google Scholar, ISI (WoS), Magiran, PubMed, Scopus, IranDoc, Science Direct, and Iran Medix were examined, using the search keywords of Paraoxonase 1, polymorphism, multiple sclerosis, and PON1. PON1 is undoubtedly a potential factor in the pathogenesis of multiple sclerosis, and it plays an important role in protecting antioxidants in the blood. Oxidative stress and lipid peroxidation are factors in the pathogenesis of MS. Both inflammatory cytokines and oxidative stress have a detrimental effect on PON1. However, reducing the activity of PON1 may help to restore the pathogenesis of the disease. Decreased PON1 activity and PON1 polymorphism are associated with several neurological diseases, including ischemic stroke, white matter lesions (WMLs), amyotrophic lateral sclerosis (ALS), dementia, and Parkinson's disease. PON1-55M alleles in Italians and PON1-192Q alleles in Poles were associated with a high risk of MS. Moreover, PON1-55 and PON1-192 polymorphisms were not associated with MS onset age, nor its evolutionary type.

Abstract 540: Effects of Pro-inflammatory High Density Lipoprotein on Nrf2 Signalling and Foam Cell Formation in Macrophage of Coronary Artery Disease Patients

Background: High density lipoprotein (HDL) from coronary artery disease (CAD) patients display proinflammatory properties, which persuades LDL oxidation and foam cell formation in monocytes/macrophages (Mo/MΦ). Nrf2/antioxidant signalling are crucial for maintaining the redox milieu, but these mechanisms are remain elusive in the setting of pro-inflammatory HDL ( pi HDL) mediated atherosclerosis and coronary artery disease (CAD). Methods: In healthy humans (n=20) and CAD patients (n=20), we assessed Nrf2 signalling, paraoxonase-1 activity, HDL function and foam cell formation in the circulating Mo/MΦ. Results: We observed a range of HDL activity (20-80%) in healthy humans, indicating that the HDL function varies among normal individuals. In comparison with functional HDL ( f HDL), pi HDL demonstrated decreased paraoxonase-1 activity (41.38±6.71 vs. 118.04±11.18; p&lt;0.05), higher levels of lipid peroxides (0.95±0.09 vs. 0.02±0.01; p&lt;0.05), higher triglyceride (75.4±6.79 vs. 31.76±4.19; p&lt;0.05) and phospholipid levels (74.09±5.9 vs. 46.47±6.11; p&lt;0.05) in CAD patients vs . healthy humans. Interestingly, we noticed an increase in MMP9 along with enhanced pi HDL in CAD patients, a previously unrecognized event, which might accelerate atherosclerosis in these individuals. Despite an increased Nrf2 nuclear translocation, we noticed significant decrease in the levels of antioxidant enzymes in the macrophages treated with pi HDL. It is likely that pi HDL mediated Nrf2 activation could be a compensatory response to ROS/oxidative stress in CAD patients, but insufficient antioxidant system might have resulted in enhanced foam cell formation. Conclusions: Taken together, these results suggest that pi HDL could be a key regulator of Nrf2 signalling in the Mo/MΦ of CAD patients. Thus, an early screening and identification of dysfunctional HDL (i.e. pi HDL) is crucial for vascular health, thereby preventing the progression of CAD.

Serum HDL Associated Antioxidant Activity in Alzheimer's Disease: Paraoxonase1 and Dysfunctional HDL.

Human serum paraoxonase1 (PON1) is a high-density lipoprotein (HDL) associated antioxidant enzymes. We aimed to research the PON1 activity in Alzheimer's disease (AD) not accompanied with any disorders and other conditions influencing the PON1 activity. We studied the PON1 activity and PON1 related lipid parameters in two groups, probable sporadic late onset AD (n:30) and those with healthy subjects (n:32). These groups were homogeneous, in which the subjects did not have any cardiovascular risk factors or other conditions affecting PON1 activity. We found increased high-density lipoprotein cholesterol (HDL-C) and significantly decreased PON1 activity in the AD patients. A patient with a PON1 activity value of ≤ 151 U/L had a 5.48-fold higher risk for AD, compared to those with a PON1 activity value of > 151 U/L. Decreased PON1 activity may play a role in the oxidative stress (OS) related pathogenesis of AD. An increased HDL-C with the decreased PON1 activity may bring the concept of dysfunctional HDL into question in the pathogenesis of AD. It may be emphasized in the pathogenesis of AD for further studies.

Paraoxonase-1 enzyme activity in rheumatoid arthritis patients: association with carotid intima-media thickness?

Objectives The aim was to find the relationship of biochemical determinants of paraoxonase-1 (PON1) enzyme activity with carotid intima-media thickness (IMT) as a surrogate marker of atherosclerotic cardiovascular (CV) disease risk in patients with rheumatoid arthritis (RA). Background There is strong correlation between patients with RA and CV morbidity and mortality that cannot be explained by traditional risk factors alone. And this could be due to abnormal function of high-density lipoproteins (HDL). HDL promotes cholesterol efflux, as well as protects low-density lipoprotein (LDL) against oxidation, and this ability has been referred to as an 'anti-inflammatory' function because the lipid oxidation products derived from LDL are highly proinflammatory. PON1 is an HDL-associated enzyme that promotes antioxidant and anti-inflammatory properties of HDL by preventing the formation of oxidized LDL and inactivating oxidized phospholipids. Patients and methods The authors conducted a case–control study, including 30 RA patients and 20 controls, enrolled in Menoufia, Egypt. B-mode Doppler ultrasound imaging to measure carotid IMT, C-reactive protein (CRP), erythrocyte sedimentation rate, lipid profile, and PON1 activity were measured. Results RA patients tended to be more dyslipidemic as evidenced by decreased HDL and increased total cholesterol, tryglycerides (TGD), and LDL, which showed increased carotid IMT and decreased PON1 activity than the control group. Patients with carotid plaque tended to be more dyslipidemic and plasma PON1 activity tended to be lower than in patients without carotid plaque. A significant correlation between plasma PON1 activity and systemic inflammation as measured by the erythrocyte sedimentation rate and hsCRP level was noted. Conclusion Our data suggest that the lower the activity of PON1, the higher the atherosclerotic CV disease risk in RA patients, as assessed by the presence of carotid plaque. There is a significant correlation between plasma PON1 activity and systemic inflammation in RA patients. Higher hsCRP levels were associated with lower PON1 activity.

Serum NOX-2 concentrations and paraoxanase-1 activity in subclinical hypothyroidism: a pilot study

Abstract Objective Subclinical hypothyroidism (SH) is one of the most prevalent endocrine disorders. Although recent data suggest an imbalanced oxidative status in SH, the mechanisms of increased oxidative stress are poorly figured out. The primary goal of this research was to analyze potential sources of ROS and the relationship between serum NOX-2 levels and paraoxonase-1 (PON-1) activity in SH. Serum lipid changes in SH patients which had been determined were compared to healthy control group. Materials and methods Thirty-one patients diagnosed with SH and 30 healthy controls were included in the study. The quantitative sandwich ELISA was used for the detection of serum NOX-2 levels. Spectrophotometric method was used to determine serum PON-1 activity. Results Higher median serum NOX-2 levels were determined in patients than in the control group (p = 0.004). Lower median serum PON-1 activity was determined in patients as to aforementioned control group (p &lt; 0.0001). As a consequence, no statistically remarkable correlation was identified between PON-1 activity and NOX-2 levels. Triglyceride (TG) concentrations were determined as superior in patients to control group (p &lt; 0.0001). Conclusion Over-production of NOX-2 and decreased PON-1 activity contribute to the increased oxidative stress in SH patients. Larger prospective studies required to confirm these findings.

Associations between paraoxonase-1 and systemic lupus erythematosus.

The objective of this analysis was to explore associations between paraoxonase-1 levels, gene polymorphisms and systemic lupus erythematosus. Meta-analyses of paraoxonase-1 levels and Q192R and L55M and polymorphisms in systemic lupus erythematosus were conducted. Nine articles were incorporated in our meta-analysis, which uncovered that the paraoxonase-1 level was decreased in systemic lupus erythematosus compared to control (standard mean difference = -1.626, 95% confidence interval = -2.829--0.424, p = 0.008). Ethnicity-specific meta-analysis demonstrated a relation tendency between decreased paraoxonase-1 activity and lupus in Europeans (standard mean difference = -1.236, 95% confidence interval = -2.634-0.163, p = 0.083). Paraoxonase-1 activity was reduced in systemic lupus erythematosus in a single Arab and African population. Decreased paraoxonase-1 activity was found in a small sample of systemic lupus erythematosus patients (standard mean difference = -1.642, 95% confidence interval = -3.076--0.247, p = 0.021). Ethnicity-specific analysis indicated a relationship between the paraoxonase-1 55 M allele in the Arab systemic lupus erythematosus population. However, a lack of association with systemic lupus erythematosus and the paraoxonase-1 192 R allele was observed. Meta-analyses revealed reduced paraoxonase-1 activity in patients with systemic lupus erythematosus and found possible associations between systemic lupus erythematosus and paraoxonase-1 L55M polymorphism in a specific ethnic group.

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

Background: Nitro-oxidative stress (NOS) has been implicated in the pathophysiology of psychiatric disorders. The activity of the polymorphic antioxidant enzyme paraoxonase 1 (PON1) is altered in diseases where NOS is involved. PON1 activity may be estimated using different substrates some of which are influenced by PON1 polymorphisms.Objectives: 1) to review the association between PON1 activities and psychiatric diseases using a standardized PON1 substrate terminology in order to offer a state-of-the-art review; and 2) to review the efficacy of different strategies (nutrition, drugs, lifestyle) to enhance PON1 activities.Methods: The PubMed database was searched using the terms paraoxonase 1 and psychiatric diseases. Moreover, the database was also searched for clinical trials investigating strategies to enhance PON1 activity.Results: The studies support decreased PON1 activity as determined using phenylacetate (i.e., arylesterase or AREase) as a substrate, in depression, bipolar disorder, generalized anxiety disorder (GAD) and schizophrenia, especially in antipsychotic-free patients. PON1 activity as determined with paraoxon (i.e., POase activity) yields more controversial results, which can be explained by the lack of adjustment for the Q192R polymorphism. The few clinical trials investigating the influence of nutritional, lifestyle and drugs on PON1 activities in the general population suggest that some polyphenols, oleic acid, Mediterranean diet, no smoking, being physically active and statins may be effective strategies that increase PON1 activity.Conclusion: Lowered PON1 activities appear to be a key component in the ongoing NOS processes that accompany affective disorders, GAD and schizophrenia. Treatments increasing attenuated PON1 activity could possibly be new drug targets for treating these disorders.