Paraoxonase Enzyme Activity Research Articles

Association of pesticide exposure with hematological parameters and cholinesterase and paraoxonase enzyme activities among avocado farmworkers in Mexico

Association of pesticide exposure with hematological parameters and cholinesterase and paraoxonase enzyme activities among avocado farmworkers in Mexico

Investigation of the effects of Terminalia chebula seed hydroalcoholic extract on Paraoxonase1 enzyme activity in rats

Background and aims: Paraoxonase 1 (PON1) is related to high-density lipoprotein (HDL) in serum and protects against low-density lipoprotein (LDL) oxidation. This study aimed to investigate the effects of Terminalia chebula on PON1 in hyperlipidemic rats and the molecular docking effects of some compounds of this medical plant on PON1 activity. Methods: Overall, 40 male rats (200–250 gr) were randomly divided into four groups, including the control group, the hyperlipid group, the hyperlipid group receiving 400 mg/kg of the hydroalcoholic extract of T. chebula seeds, and the hyperlipid group receiving 800 mg/kg of the hydroalcoholic extract of T. chebula seeds. The PON1 arylesterase activity in serum and the PON1 gene expression in the liver tissue underwent investigation. Then, the molecular docking effects of its compounds were studied on PON1 through in-silico studies using the AutoDock software (version 4.2.0). Results: T. chebula decreased (P<0.001) the serum triglycerides from 105.88±10.15 mg/dL in the hyperlipidemic group to 66.88±14.90 and 74.25±9.51 mg/dL in hyperlipidemic groups receiving 400 and 800 mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. In addition, the PON1 serum aryl esterase activity increased from 202.12±6058 in hyperlipidemic rats to 224.34±58.74 (P=0.83) and 235.80±37.05 (P=0.6) in hyperlipidemic groups receiving 400 mg/kg and 800 mg/kg of the hydroalcoholic extract of T. chebula seeds, respectively. It also demonstrated a significant effect on PON1 gene expression (P<0.001). In addition, the in-silico and docking results revealed that the main antioxidant compounds of T. chebula, such as catechin, kaempferol, and quercetin, could bind to the PON1 enzyme directly and influence the enzyme activity. Conclusion: T. chebula increased PON1 activity and PON1 gene expression. However, among the plant’s compounds, catechin, kaempferol, and quercetin played the most substantial role in the PON1 activity. It seems that these compounds can be useful as co-treatments in hyperlipidemia therapies.

Oxidative stress induction by OCPs and OPPs pesticides may cause lung cancer incidence

Background and aims Pesticides are nowadays known as one of the most important causes of human disorders worldwide. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) and organophosphorus pesticides (OPPs) in the development of lung cancer. Methods We determined the levels of seven derived OCP residues (α-HCH, β-HCH, γ-HCH, 2,4 DDT, 4,4 DDT, 2,4 DDE, and 4,4 DDE) and enzymatic antioxidant biomarkers including paraoxonase-1 (PON-1), erythrocyte’s acetylcholinesterase (AChE), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and non-enzymatic antioxidant biomarkers, including total antioxidant capacity (TAC), protein carbonyl (PC), malondialdehyde (MDA), and nitric oxide (NO) in the blood samples of 51 lung cancer patients and 51 healthy subjects as controls. Furthermore, the effects of OPP exposure on the development of lung cancer and oxidative stress (OS) are indirectly assessed by measuring AChE and PON-1 enzyme activities. Results The average values of all the measured OCPs were significantly higher in lung cancer patients when compared with healthy control subjects (p < 0.05). AChE, PON-1, GPx, and CAT activity levels, as well as the amounts of PC, MDA, and NO were higher in patients with lung cancer than in the control subjects (p < 0.05), while TAC values were lower in the patients. Moreover, our data showed a significant association between OCP concentrations and OS parameters (p < 0.05). Conclusion The results suggest that OCPs and OPPs may have a role in lung cancer incidence in southeastern Iran, and at least one of the mechanisms by which OCPs and OPPs may contribute to increasing the development of lung cancer in the studied area is through OS generation.

Vutiglabridin Modulates Paraoxonase 1 and Ameliorates Diet-Induced Obesity in Hyperlipidemic Mice.

Vutiglabridin is a clinical-stage synthetic small molecule that is being developed for the treatment of obesity and its target proteins have not been fully identified. Paraoxonase-1 (PON1) is an HDL-associated plasma enzyme that hydrolyzes diverse substrates including oxidized low-density lipoprotein (LDL). Furthermore, PON1 harbors anti-inflammatory and antioxidant capacities and has been implicated as a potential therapeutic target for treating various metabolic diseases. In this study, we performed a non-biased target deconvolution of vutiglabridin using Nematic Protein Organisation Technique (NPOT) and identified PON1 as an interacting protein. We examined this interaction in detail and demonstrate that vutiglabridin binds to PON1 with high affinity and protects PON1 against oxidative damage. Vutiglabridin treatment significantly increased plasma PON1 levels and enzyme activity but not PON1 mRNA in wild-type C57BL/6J mice, suggesting that vutiglabridin modulates PON1 post-transcriptionally. We further investigated the effects of vutiglabridin in obese and hyperlipidemic LDLR-/- mice and found that it significantly increases plasma PON1 levels, while decreasing body weight, total fat mass, and plasma cholesterol levels. Overall, our results demonstrate that PON1 is a direct, interacting target of vutiglabridin, and that the modulation of PON1 by vutiglabridin may provide benefits for the treatment of hyperlipidemia and obesity.

The usefulness of arylesterase in predicting contrast-induced nephropathy in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention

Aim: Oxidative stress is one of the causes of contrast-induced nephropathy (CIN). Paraoxonase1 (PON1), is one of the oxidative stress markers. The most sensitive method that has been in use to measure PON1 enzyme activity is the measurement of arylesterase (AREase) activity. To explore relationship between AREase activity and CIN development.&#x0D; Material and Method: A total of 58 STEMI patients were included in our study. The patients were divided into two groups as CIN (+) and CIN (-). The success of AREase activity level in predicting the development of CIN was also examined by using ROC analysis.&#x0D; Results: Out of the study patients, 13 were CIN (+) and 45 were CIN (-). AREase activity was found to be statistically significantly lower in the CIN (+) group (875 U/L vs 819 U/L, p= 0.004). In the regression analysis, diabetes mellitus, contrast volume and AREase activity were determined as independent risk factors in the development of CIN. As a result of the ROC analysis, we concluded that the AREase activity level

THE COMPLEX RELATIONSHIP OF PARAOXONASE GENE POLYMORPHISMS WITH CORONARY ARTERY DISEASE AND LIPID METABOLISM

Cardiovascular disorder (CVD) is one of the major reasons for mortality in developing and developed countries. According to the World Health Organization (WHO), non-communicable diseases (NCDs) are responsible for 50% of the overall disease burden in Pakistan. And among the NCDs, the most prevalent disease is CVD, as approximately every 1 out of 4 adults suffered from coronary artery disease (CAD). Coronary artery disease mainly causes ischemia or hypoxia of the heart due to coronary vessels stenosis or atherosclerosis.1 The key risk factors include smoking, dyslipidemia, hypertension, obesity, family history, and type 2 diabetes mellitus. The genetic contribution to CAD is an independent factor that includes genetic polymorphisms such as single nucleotide polymorphisms (SNPs). Genome-wide association studies (GWAS) suggest many genes SNPs involved in the pathogenesis of coronary artery disease.2 Although many studies identified the genes and single nucleotide polymorphisms but still, the role of these genetic factors is not clearly understood. Paraoxonase (PON) gene cluster is one of the most widely studied genes that consist of three genes PON1, PON2, and PON3, and located on chromosome 7. The PON2 is the oldest gene among this cluster however, all the 3 genes have a high structural homology. The International Union of Biochemistry and Molecular Biology classified the paraoxonases as aryldialkyl phosphatases. The enzymes coded by these gene clusters exhibit the antiatherosclerotic properties that play an essential role in high-density lipoproteins (HDL) or antioxidant properties. The PON1 activity is highly influenced by both genetic (non-modifiable) and environmental factors (modifiable).3 It involves a complex interaction between both genetic and modifiable factors. The human PON1 is a calcium-dependent glycoprotein that is first identified by its ability to hydrolyze various organophosphates. Through lipid peroxides hydrolysis, it reduces the low-density lipoprotein (LDL). Low enzyme levels are associated with cardiac disorders, familial hypercholesterolemia, and diabetes mellitus. To date, approximately 184 SNPs reported, and some coding region SNPs i.e. rs662 and rs854560 are the most widely studied single nucleotide polymorphisms.4 The most commonly studied Q192R polymorphism is associated with poor patient outcomes. The risk allele or R allele is associated with abnormal HDL and triglycerides levels and the worst CVD outcome. Furthermore, the levels of paraoxonase levels are also decreased in CVD patients and there is a complex relationship between different variables particularly genetic markers, lipid profile, or environmental factors with PON activity.5 The PON2 and PON3 similarly play a crucial role in lipid metabolism and inhibit atherosclerosis due to their protective role against the formation of atherosclerotic plaques in coronary arteries. In PON2 rs12704796 is significantly associated with coronary heart disease risk.6 Robertson et al. first reported single nucleotide polymorphism in PON3 at positions number 107 and 99 but the exact mechanism of these SNPs in the pathophysiology of CAD remains to be understood.7 The multi-locus model also revealed a gene to gene interaction between PON2 and PON3 and gene-environment in the Pakistani cardiac patients.8 The single nucleotide polymorphisms in this gene cluster are significantly important in CAD patients. These SNPs may exert their effect by modulating the lipid metabolism and enzyme concentrations in CAD patients, which can be varied according to certain environmental factors and ethnic groups. Thus, in the future, it is suggested to perform a study with more sample size in different populations that can help us in better understanding disease pathophysiology and prevention.

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development.

Paraoxonase 1 (PON1) is calcium-dependent aryldialkylphosphatase, thought to possess; anti-oxidant, anti-adhesion, anti-inflammatory, anti-thrombosis and anti-apoptosis effects, as well as lipid-modifying properties. Numerous clinical studies have shown associations between different PON1 polymorphisms and different cardiovascular pathologies. The rs622 (c.575A > G) and the rs854560 (c.163A > T) are the most studied PON1 SNPs in the coding region, with rs705381 (− 162A/G), rs854572 (− 909G/C) and rs705379 (− 108C/T) being the most studied SNPs in the regulatory PON1 gene region. The three major PON1 activities are aryldialkylphosphatase, arylesterase and lactonase activity. The different SNPs affect PON1 serum concentrations and enzyme activity, thus leading to pro-/anti-atherogenic effects. In that setting, it is very difficult to establish as to whether the genotype or phenotype of PON1 is primarily associated with cardiovascular risk. Given the current scientific evidence, PON1 genotyping might be reasonable in patients with high and very high cardiovascular risk.

Phytochemicals as Modulators of Paraoxonase-1 in Health and Diseases

Chronic diseases such as cardiovascular disease (CVD), atherosclerosis, chronic liver disease, and neurodegenerative diseases are major causes of mortality. These diseases have gained much attention due to their complications, and therefore novel approaches with fewer side effects are an important research topic. Free radicals and oxidative stress are involved in the molecular mechanisms of several diseases. Antioxidants can scavenge free radicals and mitigate their adverse effects. One of the most important antioxidant enzymes are paraoxonases (PONs). These enzymes perform a wide range of physiological activities ranging from drug metabolism to detoxification of neuroleptics. Paraoxonase-1 (PON1) is produced in the liver and then transferred to the bloodstream. It has been demonstrated that PON1 could have beneficial effects in numerous diseases such as atherosclerosis, CVD, diabetes mellitus, and neurodegenerative diseases by modulating relevant signalling pathways involved in inflammation and oxidative stress. These pathways include peroxisome proliferator-activated receptor gamma (PPAR-γ) and protein kinase B/nuclear factor kappa-light-chain-enhancer of activated B cells (AKT/NF-κB)-dependent signalling pathways. Increasing PON1 could potentially have protective effects and reduce the incidence of various diseases by modulating these signalling pathways. Several studies have reported that dietary factors are able to modulate PON1 expression and activity. This review aimed at summarizing the state of the art on the effects of dietary phytochemicals on PON1 enzyme activity and the relevant signalling pathways in different diseases.

A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease.

Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in the biomedical field. PON substrates are classified as organophosphates, aryl esters, and lactones based on their structure. While the established native physiological activity of PONs is its lactonase activity, the enzymes’ exact physiological substrates continue to be elucidated. All three PONs have antioxidant potential and play an important anti-atherosclerotic role in several diseases including cardiovascular diseases. PON3 is the last member of the family to be discovered and is also the least studied of the three genes. Unlike the other isoforms that have been reviewed extensively, there is a paucity of knowledge regarding PON3. Thus, the current review focuses on PON3 and summarizes the PON substrates, specific activities, kinetic parameters, and their association with cardiovascular as well as other diseases such as HIV and cancer.

The effect of Paraoxonase gene polymorphisms and paraoxonase enzyme activity on Non-Hodgkin lymphoma

Non-Hodgkin Lymphoma (NHL) is a malignant lymphoproliferative disease. Antioxidant paraoxonase enzyme (PON1) has a vital role in the elimination of potential carcinogenic organophosphate molecules. The polymorphisms in the PON1 gene, especially Q192R and L55M, may affect negatively the activity and synthesis of PON1 enzyme. The aim of this study was to evaluate the effect of these polymorphisms together with PON1 enzyme activity on NHL. We surveyed these polymorphisms together with PON1 enzyme activity in 93 patients with NHL and in 93 healthy individuals by real-time polymerase chain reaction (RT-PCR) and spectrophotometer. Although carrying the M and R alleles of L55M and Q192R polymorphisms increases the risk of NHL, they were not significant. Furthermore, the NHL patients carrying 192 R allele had significantly lower enzyme activity than controls having same allele (P = 0.025). This research is the first study worldwide investigating the effect of Q192R and L55M polymorphisms on PON1 enzyme activity in NHL disease. The risk of developing NHL may be further increased in individuals with low enzyme activity having R risk allele of the Q192R polymorphism. The present study suggests that these polymorphisms in NHL disease should be analyzed together with PON1 enzyme activity in larger populations. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2022.2052315 .

Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression, anxiety and psychosis.

BACKGROUNDTemporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase 1 (PON1) status may occur in TLE and these psychiatric conditions. AIMTo examine PON1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in TLE.METHODSWe recruited 40 normal controls and 104 TLE patients, 27 without comorbidities and 77 with comorbidities including mood disorders (n = 25), anxiety disorders (n = 27) and psychosis (n = 25).RESULTSFour-(chloromethyl)phenyl acetate hydrolysis (CMPAase) and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than those in normal controls. The areas under the receiver operating characteristic curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (± 0.037) for MTS. Partial least squares path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (P < 0.0001) and psychopathology (P < 0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination score. CONCLUSIONThe severity of TLE and comorbidities are to a large extent explained by reduced PON1 enzyme activities and by effects of the Q192R genotype, which are mediated by reduced CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Evaluation of Oxidative Stress and Inflammatory Biomarkers Pre and Post-Treatment in New Diagnosed Atherosclerotic Patients

ABSTRACT Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. It is characterized by lipid accumulation in the arterial wall, increased hyperlipidemia, oxidative stress, lipid peroxidation, and protein oxidation. Our study included 45 patients ages of 40–60 and 45 healthy volunteers with similar demographic characteristics without any chronic disease as well. Fasting plasma glucose, BUN, creatinine, LDL-cholesterol, HDL-cholesterol, triglyceride, total cholesterol, HbA1c, and C-reactive protein (CRP) levels were measured using commercial kits by autoanalyzer. The oxidative stress biomarkers total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT), catalase (CAT), paraoxonase (PON1), and arylesterase (ARES) enzyme activities were measured using photometric methods. The inflammatory biomarkers interleukin 1 beta (IL-1β), tumor necrosis factor-α (TNF-α), presepsin (PSPN), and raftlin (RFTN1) levels were measured with ELISA Kits. Oxidative stress index (OSI) and disulfide (DIS) were calculated. The clinical, biochemical biomarkers such as BUN, creatinine, HDL, LDL, total cholesterol, triglyceride, and CRP levels were found to be higher than the control group and lower post-treatment compared to the pre-treatment group (p <0.001). The oxidative stress parameters, TOS, OSI, and DIS levels were found to be higher than the control group, and the levels before the treatment were statistically significantly higher than after the treatment (p < 0.001).Antioxidant biomarkers TAS, TT, and NT levels were low in the patient group. Inflammatory biomarkers were highest before treatment and decreased with treatment. Oxidative stress and inflammation, which increased in atherosclerosis patients may guide disease prognosis and treatment strategies.

Changes in serum PON1 activity, gene expression and their association with lipid profile parameters in healthy Darehshori neonatal foals: a preliminary study

Paraoxonase 1 (PON1) contributes to the antioxidant mechanisms that prevent lipoprotein oxidation and act as a negative acute-phase protein. This study aimed to evaluate changes in serum PON1 activity, the leukocyte PON1 gene expression, as well as lipid profile tests (LDL, HDL, triglyceride, and cholesterol) in 16 healthy Darehshori newborn foals up to 60 days of life. Blood samples were collected at 1, 7, 15, 30, and 60 days used for detecting biochemical parameters, PON1 activity, and, and its gene expression, using realtime RT-PCR. Low levels of PON1 activity were observed at birth, which increased significantly with increasing age at days 7, 15, 30, and 60. In addition, HDL levels were significantly increased at 15, 30, and 60 days in male foals, and in contrast, LDL and cholesterol levels were significantly reduced on days 15, 30, and 60 compared to the first day of life in newborn foals. For the first time, PON1 mRNA was detected in foal leukocytes and its gene expression showed a significant decrease compared to the birthday. The positive correlations between PON1 expression/HDL, LDL, and cholesterol in the first week of life and between PON1 enzyme activity/ HDL, LDL, and cholesterol in different samples and sexes may indicate an adaptive increase in antioxidant defenses in response to oxidative stress. The authors suggest that PON1 expression in leukocytes may be related to the enzyme?s ability to reduce intracellular oxidant levels.

Palamut (Sarda sarda) balığında paraoksonaz (PON) enzim aktivitesi üzerine cıva, bakır ve çinkonun etkisi

Since heavy metal dirtiness, which we frequently encounter in environmental pollution causes harmful effects on the organism through biochemical enzyme reactions, in this study, the effects of mercury (Hg+2), copper (Cu+2), and zinc (Zn+2) heavy metal ions, which are common in environmental pollution, on PON (paraoxonase) enzyme activity in muscle tissue of bonito (Sarda sarda) were investigated. In the study, 25 bonito (S. sarda) fish muscle tissues freshly obtained from the Samsun region sea were used. The changes in PON enzyme activity were determined by adding different volumes of heavy metal solutions. PON enzyme activities of Hg+2 heavy metal ion used in different volumes were calculated as 30.9383 U/mLdak, 29.0598 U/mLdak, 26.3799 U/mLdak, 23.9443 U/mLdak, 20.6725 U/mLdak, PON enzyme activities of Cu+2 heavy metal ion used in different volumes were calculated as 19.7949 U/mLdak, 19.4807 U/mLdak 19.1864 U/mLdak, 19.1200 U/mLdak, 18.9037 U/mLdak and PON enzyme activities of Zn+2 heavy metal ion used in different volumes were calculated as 23.8305 U/mLdak, 23.0781 U/mLdak, 22.9073 U/mLdak, 22.4324 U/mLdak, 21.8159 U/mLdak. As a result of these obtained data, activity (%) values were calculated and activity (%) graphs were drawn. As a result of the study, it was determined that increasing concentrations of Cu+2 and Zn+2 heavy metal ions caused a decrease in PON enzyme activity, but there was no statistically significant difference between the different concentrations used. It was determined that increasing concentrations of Hg+2 heavy metal ion inhibited the PON enzyme activity, caused a statistically significant decrease between the activities depending on the different concentrations used (p &lt; 0.05).

Ophthalmic drugs: in vitro paraoxonase 1 inhibition and molecular docking studies.

Glaucoma is a neuropathy disorder and is generally treated by drugs. Allergic conjunctivitis is a common ophthalmologic disease. Paraoxonase 1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. PON1 is known for preventing atherosclerosis through lipid-modifying features, as well as which has decisive actions of antiapoptosis, anti-inflammatory, antithrombosis, and antiadhesion antioxidant activity properties. Thus, reducing the enzyme levels in hyperthyroidism, chronic renal failure, glaucoma, diabetes mellitus, and cardiovascular diseases is a significant risk. This study was tested some ophthalmic drugs used to treat the diseases, such as glaucoma and allergic conjunctivitis, mentioned above, travoprost, latanoprost, ketotifen, emedastine, and olopatadine, for their inhibition activities against PON1. These drugs displayed the potent inhibition effect with IC50 values ranging between 14.95 ± 0.15 and 299.60 ± 4.07 μM and KI constants ranging from 9.71 ± 2.63 to 261.50 ± 59.98 μM. Besides, the molecular docking analyses of the competitive inhibitors, travoprost, emedastine, and olopatadine, were performed to understand the binding interactions on the enzyme's binding site. According to both in vitro and in silico analysis results, travoprost had the most potent effect on PON1 enzyme activity.

The Effects of Bioavailability-Enhanced Curcuminoids on Serum Paraoxonase-1 Activity in Patients with Metabolic Syndrome

Introduction: Metabolic syndrome (MetS) is characterised by a clustering of metabolic cardiovascular disease (CVD) risk factors that include: central obesity, impaired glucose metabolism, dyslipidaemia (hypertriglyceridemia, increased low-density lipoprotein [LDL], decreased high-density lipoprotein [HDL]) and hypertension. Paraoxynase-1 (PON1) is a plasma HDL associated protein that inhibits the oxidation of other lipoproteins. There is some evidence of reduced enzyme activity in subjects with metabolic syndrome. Curcumin is a natural polyphenol, it has been reported that curcumin has beneficial effects on several metabolic syndrome associated parameters. The aim of this study was to evaluate the effect of phospholipid complex of curcumin as an antioxidant on the activity of this enzyme in subjects with metabolic syndrome.Materials and method: A double-blind randomised control study was undertaken in 80 patients with metabolic syndrome. Subjects in the intervention (n = 40) were given capsules of phospholipidated curcumin (1 g/day) for a period of 6 weeks. The control subjects (n = 40) received a placebo. Fasting blood samples of each person were obtained during the start and the end of the study. Paraoxonase activity was measured using a PON1 fluorescence Paraoxonase Assay Kit and Arylesterase activity was measured by photometeric method using a UV-Visible spectrophotometer.Results: Serum paraoxonase enzyme activity did not change significantly between the curcumin treated group and the control group before the intervention (0.54 ± 0.18 U/µl versus 0.49 ± 0.14 U/µl; P > 0.05), nor did serum arylesteras activity change significantly between two study groups (152.67 [46.60 to 916.05] U/µl versus 129.77 [55.34 to 344.78] U/µl; P > 0.05). In addition, there was no significant difference in changes at baseline and after the intervention in serum PON1 activity between the curcumin treated group and the control group (-0.03±0.19 U/µl versus -0.04±0.18 U/µl; P > 0.05), nor was there a significant change in arylesteras activity (-12.36 [-88.83 to 110.24] U/µl versus -4.58 [-61.06 to 47.07] U/µl; P > 0.05).Conclusion: Phospholipid fortified curcumin has no significant effect on serum PON1 activity.

Paraoxonase 1: Could it be important for asthma in children?

Objective: The paraoxonase 1 (PON-1) enzyme is an important antioxidant. The balance between oxidative stress and antioxidant defense mechanisms is disturbed during asthma attacks. The activity of the PON-1 enzyme is related to PON-1 gene polymorphism. This study aimed to evaluate the activity of PON-1 enzyme and Q192R polymorphism in asthmatic children. Material and methods: During the 2013-2014 period, we performed a prospective study with 34 asthmatic (study group) and 34 healthy (control group) children. Serum PON-1 activity was evaluated in the study group at the onset of an asthma attack and at the end, and also in the control group. Q192R gene polymorphism of asthmatic children, which is known to affect the PON-1 enzyme activity was also investigated. Results: There was no significant difference in terms of serum PON-1 enzyme activity and PON-1 gene polymorphism between the asthmatic children and healthy controls. However, a significant increase was observed at the PON-1 enzyme activity of asthmatic children at the end of the asthma attack compared to its onset. Conclusion: The PON-1 enzyme activity and Q192R genetic polymorphism in asthmatic children are not different from those of healthy children, but PON-1 enzyme activity is higher at the end of an asthma attack compared to the onset. PON-1 enzyme, as a member of the antioxidant mechanism, may be important both in understanding the pathophysiology of asthma and in the development of new medications for asthma.

Abnormal paraoxonase-1 (PON1) enzyme activity in idiopathic inflammatory myopathies.

Patients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients. A total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes. The arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes. The arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

A targeted multi-omics approach reveals paraoxonase-1 as a determinant of obesity-associated fatty liver disease

BackgroundThe multifactorial nature of non-alcoholic fatty liver disease cannot be explained solely by genetic factors. Recent evidence revealed that DNA methylation changes take place at proximal promoters within susceptibility genes. This emphasizes the need for integrating multiple data types to provide a better understanding of the disease’s pathogenesis. One such candidate gene is paraoxonase-1 (PON1). Substantial interindividual differences in PON1 are apparent and could influence disease risk later in life. The aim of this study was therefore to determine the different regulatory aspects of PON1 variability and to examine them in relation to the predisposition to obesity-associated fatty liver disease.ResultsA targeted multi-omics approach was applied to investigate the interplay between PON1 genetic variants, promoter methylation, expression profile and enzymatic activity in an adult patient cohort with extensive metabolic and hepatic characterisation including liver biopsy. Alterations in PON1 status were shown to correlate with waist-to-hip ratio and relevant features of liver pathology. Particularly, the regulatory polymorphism rs705379:C > T was strongly associated with more severe liver disease. Multivariable data analysis furthermore indicated a significant association of combined genetic and epigenetic PON1 regulation. This identified relationship postulates a role for DNA methylation as a mediator between PON1 genetics and expression, which is believed to further influence liver disease progression via modifications in PON1 catalytic efficiency.ConclusionsOur findings demonstrate that vertical data-integration of genetic and epigenetic regulatory mechanisms generated a more in-depth understanding of the molecular basis underlying the development of obesity-associated fatty liver disease. We gained novel insights into how NAFLD classification and outcome are orchestrated, which could not have been obtained by exclusively considering genetic variation.

Abnormal levels of apolipoprotein A-I in chronic thromboembolic pulmonary hypertension.

Recent studies have shown low high-density lipoprotein cholesterol (HDL-C) and dysregulated lipid metabolism in chronic thromboembolic pulmonary hypertension (CTEPH). Apolipoprotein A-I (ApoA-I) is the major protein component of HDL-C and mediates most of its functions. We hypothesize that ApoA-1 and its oxidative state might be more sensitive biomarkers in CTEPH. Plasma levels of HDL-C, ApoA-I, paraoxonase-1 enzyme activity (PON1), and the oxidized dysfunctional ApoA-I (oxTrp72-ApoA-I) were measured in patients with CTEPH and compared to those in healthy controls. Association with markers of disease severity in CTEPH was assessed. We included a total of 61 patients with CTEPH (age: 61.2 ± 15 years; male 52.5%) and 28 control subjects (age: 60.1 ± 8 years; male 59.3%). When adjusting for age, sex, body mass index, and statin use, ApoA-I was lower in CTEPH compared to controls (CTEPH:125.2 ± 27 mg/dl; control:158.3 ± 29.4 mg/dl; p < 0.001), but HDL-C levels were not statistically different. There were no significant differences in PON and oxTrp72-ApoA-I/ApoA-I ratio. In exploratory analyses, ApoA-I was associated with mean right atrial pressure (rs = −0.32, p = 0.013) and N-terminal pro B-type natriuretic peptide (rs = −0.31, p = 0.038). There were no significant associations between HDL-C, PON1, or oxTrp72-ApoA-I/ApoA-I ratio and markers of disease severity. We conclude that ApoA-I is a more sensitive biomarker than HDL-C in CTEPH, and may be associated with right heart dysfunction.