Paraoxonase Research Articles

Effect of Dialyzer Reuse on the Activity of Paraoxonase 1 in Patients on Hemodialysis.

Cardiovascular disease is the major cause of mortality in patients undergoing chronic hemodialysis treatment. The oxidative modification of low-density lipoprotein is a crucial step in the pathogenesis of atherosclerosis. Paraoxonase 1 (PON1) is the protein responsible for most of the antioxidant activity of high-density lipoprotein, and its reduced levels are associated with more cardiovascular events in several populations. In hemodialysis patients, reduced PON1 activity has been shown to be associated with increased cardiovascular mortality. Studies have shown that after the hemodialysis session, the activity of PON1 increases. The influence of dialyzer reuse on the activity of PON1 is unknown. We aimed to evaluate the effect of the reuse of two types of dialyzers (polynephron and polyethersulfone) on the PON1 activity of hemodialysis patients. A total of 30 patients on hemodialysis were included. Pre- and post-dialysis blood samples were collected to analyze the activity of PON1 in thefirst use of the dialyzer and in the hemodialysis session of its sixth reuse. This process was carried out with polynephron (bisphenol-free) and polyethersulfone dialyzers. We found that post-dialysis PON1 activity was significantly higher than pre-dialysis activity in both thefirst use and sixth reuse (P < 0.001). The practice of reusing the dialyzer did not interfere with the improvement of PON1 activity after the hemodialysis session.

Association of paraoxonase 1 activity and insulin resistance models in type 2 diabetes mellitus: Cross-sectional study.

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Chronic hyperglycemia induces reactive oxygen species and increases oxidative stress. Human serum paraoxonase-1 (PON-1) is an enzyme synthesized in the liver, and it is an antioxidant enzyme with a beneficial role in fighting oxidative stress. The objective of the study was to compare PON-1 activity in type 2 diabetes mellitus (T2DM) and nondiabetics, as well as to find the association between PON-1 activity and different insulin resistance (IR) models in diabetics. The cross-sectional study recruited 100 diabetic and 100 age and gender-matched controls. Fasting blood glucose, insulin, and C-peptide, were assayed. PON-1 activity was measured by the spectrophotometric method. Various insulin resistance models based on insulin and C-peptide were constructed using appropriate formulae. Receiver operating characteristic was constructed to find if PON-1 can be a good marker for diabetes. PON-1 activity was found to be significantly higher (p < 0.0001) in diabetics compared to controls. Highly significant hyperinsulinemia (p < 0.0001) was noted in diabetics. C-peptide levels were significantly lower in cases (p = 0.0215) as compared to controls. Homeostasis model assessment (HOMA)-IR C was insignificantly higher in cases. HOMA B cell, HOMA 1% B cell, and C-peptide-based IR (CIR) were significantly lower in cases (p < 0.0001 and p = 0.002), respectively, as compared to controls. An odds ratio of 3.15 was obtained, which suggests that the risk of T2DM is 3 times higher in subjects with elevated PON-1 levels. Chi-square showed a significant association (p = 0.0001) between DM and PON-1 levels; the chi-square statistic value (with Yates correction) was 14.49. Correlation data showed that PON-1 activity had a significant negative correlation with quantitative insulin sensitivity check index (r = -0.265, p = 0.019). A significant negative correlation (r = -0.22, p = 0.016) was also seen between PON-1 and CIR (HOMA-IR C). There was no significant correlation seen between PON-1 and other IR models. It can be concluded from our study that PON-1 activity is elevated in T2DM patients, which can be a beneficial marker.

The impact of Diplazium esculentum on the activities of cholinesterase, paraoxonase-1, and malondialdehyde in vegetable farmers who use pesticides

Background: .The use of pesticides in the world is currently increasing and even uncontrolled and poses a risk of pesticide poisoning for farmers. Diplazium esculentum is a biodiversity in Indonesia and contains active compounds include steroids, triterpenoids, phenols, flavones and high antioxidant potential, which contains flavonoid compounds that have the potential to reduce pesticide poisoning Aim: This study aims to determine the effect of Diplazium esculentum on enzyme cholinesterase activity, paraoxonase-1 (PON1) activity and malondialdehyde (MDA) activity in farmers exposed to pesticides. Methods: This study used a Randomized Controlled Trial (RCT) experimental design, in which the researcher divides research samples between the experimental and control groups at random using double-blind criteria. Using the enzyme-linked immunosorbent assay (ELISA) method, cholinesterase activity, paraoxonase-1 (PON1), and malondialdehyde (MDA) test are examined. There were 375 participants in this study, all of whom were pesticide-using vegetable growers in Kanreapia Village, Tombolopao District, Gowa Regency. 42 persons served as samples, although (21 people in the intervention group and 21 people in the control group). Results: Results showed that Diplazium esculentum had a significant effect on cholinesterase and paraoxonase-1 (PON1) activity in the intervention group compared to the control group. However, there was no significant effect on malondialdehyde (MDA) levels in pesticide-using vegetable farmers. Conclusions:&nbsp; There is an effect of Diplazium esculentum on enzyme cholinesterase, and paraoxonase-1 (PON1) activity, and there is no effect of Diplazium esculentum on malondialdehyde (MDA) in farmers exposed to pesticides.

Paraoxonase 1 -L55M polymorphism and coronary heart disease risk in the Chinese population: evidence from a meta-analysis

Many studies have examined the association between paraoxonase 1 (PON1) -L55M polymorphisms and risk of coronary heart disease (CHD), but the results remained inconsistent. We therefore aimed to address this association by performing an updated meta-analysis in the Chinese population. The PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure were searched up to May 2020. The strength of statistical association was assessed with odds ratio (OR) and 95% confidence interval (CI). A total of eight studies with 1826 CHD cases and 1817 controls were finally included in the analysis. In the overall and subgroup analyses by control sources and geographic areas, the results showed no significant associations with CHD among all analysis models. Furthermore, we performed the analysis by including or excluding the HWE-violating studies. The results suggested that the MM genetype were significantly associated with CHD in studies not consistent with HWE under recessive and dominant models. This meta-analysis demonstrates that the PON1 -L55M polymorphism may not be associated with CHD risk in the Chinese population. Further studies with strict selection of patients and controls in different ethnic populations will be required to clarify this finding.

Clinicoradiological evaluation of oxidative stress activity in acute cerebral infarction in the first 24 h and the qualitative importance of dysfunctional HDL in stroke.

Acute cerebral infarction (ACI) occurs as a result of instant disruption of vascular flow that causes disbalance between oxidative/antioxidative activity. We examined the relationship of serum neuro-oxidative stress parameters with stroke severity and infarct volume in ACI and emphasized the qualitative importance of high-density lipoprotein (HDL) on its relationship with myeloperoxidase (MPO) and paraoxonase-1 (PON1) in the acute period of stroke. One hundred ACI patients applied within the first 24 h and 50 healthy volunteers were included. The patient group was evaluated with demographic data (including arrival serum biochemical assessment), clinical disability scores, infarct volume, serum oxidative/antioxidative parameters (lipid hydroperoxide (LOOH), MPO, PON1, MPO/PON ratio). The relevant serum parameters were compared with the control group. Dysfunctional HDL measurement was based on detecting dysfunctionality as a result of a high positive correlation between the dysfunctional feature of HDL and the MPO/PON ratio. The correlation of serum parameters, clinical disability score, and infarct volume were evaluated, and independent analyses of variability with comorbidities were performed. A negative correlation between PON1 and arrival NIH score/scale (NIHSS), LOOH and discharge modified rankin scale (mRS), triglyceride level, and infarct volume; a positive correlation between MPO\PON ratio and infarct volume was determined. Logistic regression analyses showed that hypertension, diabetes, and high HbA1C may be predictors of stroke severity, and diabetes mellitus, high HbA1C, infarct volume, and high NIHSS score may be predictors of early disability (p < 0.005). The ROC curve analysis revealed that determining the cut-off value for LOOH is of importance in determining early disability scores (7.2 and 6.2, respectively). The balance between oxidative and antioxidative stress parameters and their quantitative/qualitative changes is of importance, especially in the acute period of ACI. Dysfunctional HDL's evolution and its relationship with other oxidants are significant not only in the cardiovascular aspect but also in the clinicoradiological aspect.

Neopterin, procalcitonin, total sialic acid, paraoxonase-1 and selected haematological indices in calves with aspiration pneumonia

This study aims to determine serum neopterin, procalcitonin, total sialic acid (TSA), paraoxonase-1 (PON1), and some haematological indices in calves with aspiration pneumonia (ASP). The patient group consisted of 30 calves of the Simmental breed, 0–28 days old, diagnosed with ASP upon clinical examination, anamnesis, auscultation examination, and radiographic results. The control group consisted of 10 healthy calves, otherwise with the same characteristics. A significant difference was found between calves with ASP and the control group of calves in serum iron (Fe, P &lt; 0.001), total iron-binding capacity (TIBC, P &lt; 0.05), PON1, TSA, procalcitonin, neopterin, and total leukocyte count (WBC) indices as a result of the analyses (P &lt; 0.001). Serum procalcitonin concentration was found to be 285.71 ng/ml in the ASP group and 30.34 ng/ml in the control group. Serum neopterin concentration was found to be 37.68 nmol/l in the ASP group and 15.14 nmol/l in the control group. Serum procalcitonin, neopterin, and TSA concentrations were found to be significantly higher in the ASP group compared to the control group. It was concluded that biomarkers such as serum procalcitonin, neopterin, and TSA are high in calves with ASP, and as a result, these markers provide diagnostically and prognostically important information.

Paraoxonase-1 and fetuin-A levels in children with cerebral palsy.

Studies mostly focused on risk factors and clinical status in children with cerebral palsy (CP). Various antiinflammatory markers may help us in the early diagnosis and clinical classification of cerebral palsy patients. In this study, the relationship between antiinflammatory marker levels and clinical status in patients with CP is determined. It is the first time that Fetuin-A and Paraoxonase-1 (PON-1) are examined in children with CP. The study is conducted on 79 children which are divided into two groups as CP and control. Gross motor function and spasticity are evaluated in addition to biochemical parameters. There is a statistically significant difference between CP and control group in terms of PON-1 activity, high sensitive C-Reactive Protein, HDL, and total cholesterol levels. There is no statistically significant difference in Fetuin A levels between the two groups. In suspected CP patients less than 24 months of age who possess prenatal and postnatal risk factors, the determination of PON-1 activity can be considered as a biomarker to support early diagnosis.

Paraoxonase 1 activity in the sperm-rich portion of boar ejaculates is positively associated with sperm quality

Associations of the activity of the paraoxonase 1 (PON1) enzyme with boar sperm quality still needs to be characterized, since boar ejaculates present distinct portions with differences in sperm concentration and quality. This study evaluated PON1 activity in the serum, in the distinct portions of boar ejaculates and estimated correlations with sperm quality parameters. Ejaculates and blood samples were collected from six boars for three weeks (two per week per boar; n = 36). Serum and post-spermatic portion PON1 activities were positively correlated (P = 0.01) but were both uncorrelated with the PON1 activity in the sperm-rich portion and in the whole ejaculate (P > 0.05). Differences in PON1 activity among boars were only observed in the sperm-rich portion of the ejaculate (P < 0.05). The PON1 activity in the serum and in the post-spermatic portion was generally negatively correlated with parameters of spermatozoa kinetics (P < 0.05). In the sperm-rich portion, PON1 activity was positively correlated with sperm concentration (P < 0.0001), curvilinear distance and velocity (both P < 0.05) and DNA integrity (P < 0.05), but negatively correlated with straightness and linearity (P < 0.05). Thus, boar ejaculates with increased PON1 activity in the sperm-rich portion may present increased concentration and spermatozoa with acceptable curvilinear velocity and distance and DNA integrity, which suggests that PON1 activity may be a biomarker for potential fertility.

Oxidative Stress and Changes of Important Metabolic Gene Expressions as a Potential Biomarker in the Diagnosis of Atherosclerosis in Leukocytes.

IntroductionPresenilin 1 (PSEN1), catalase (CAT), glutathione-S-transferase (GST) and paraoxonase 1 (PON1) play a vital role in prediction, diagnosis and therapy of metabolic disorders.MethodsMetabolic enzyme activities and lipid peroxidation in serum of cerebrovascular diseases (CVD) and coronary artery diseases were measured by spectrophotometric methods. mRNA was isolated from leukocytes of the patient group and healthy adult patients. Quantitative gene expression of PSEN1, CAT and GST mRNA was identified by quantitative real-time polymerase chain reaction (qPCR).ResultsThe PSEN1, CAT and GST expression in patients showed significant differences compared to the control group. PSEN1 expression in leukocytes was significantly about twice as high as that of the control group in patients with CVD. The GST, CAT and PON1 activity showed significant differences in patient groups compared to the control group.ConclusionThe mRNA expression levels can be used as a potential biomarker in the diagnosis of atherosclerosis that occurs as a result of the metabolic disorder. In atherosclerotic patients, antioxidant status is independently related to an increased risk of cardiovascular events. Antioxidant activities and mRNA expressions may have predictive value, as well as available risk factors.

Enzymatic activity of paraoxonase depending on polymorphism Q192R of the PON1 gene in patients with primary open-angle glaucoma

To genotype patients with primary open-angle glaucoma (POAG) by the Q192R polymorphism of the PON1 gene in order to identify their genetic predisposition to dyslipidemia and atherosclerosis, as well as to determe the possibility of correcting the reduced activity of the PON1 enzyme in the examined individuals by the complex drug Cytoflavin. The study included 25 men with advanced POAG, IOP compensated by hypotonic agents, and 20 volunteers without POAG (mean age 63.0±5.4 years). All subjects underwent genotyping by the Q192R polymorphism of the PON1 gene using an analyzer. PON1 activity was assessed by the rate of nitrophenol formation when paraoxone diluted in acetone was added to the blood plasma. At the second stage, patients (of different phenotypes) were prescribed the complex drug Cytoflavin. Homozygous carriers of the 192R allele were found to have significantly lower levels of PON1 activity than homozygous carriers of the Q192 allele. Carriage of the 192R allele may determine an increased risk of atherosclerotic injury in patients with POAG, especially in cases with high levels of atherogenic blood lipoproteins, low levels of high-density lipoproteins, or high levels of peroxidized lipids in the blood. The drug Cytoflavin showed a positive therapeutic effect on oxidative stress and hypercholesterinemia in POAG patients. These findings can be used to determine the atherogenicity of lipoproteins and the progression of glaucomatous optic neuropathy and to optimize the therapy of PAHO.

Measurement of paraoxonase and telomerase enzymes and HDL (high density lipoprotein) values and research of their possible relationships with each other in bloodserum of obese cats

Today, obesity is seen as a serious health problem in domestic cats. Paraoxonase1 (PON1) is a negative acute phase protein with anti-inflammatory properties. PON1 is transported by linking to different parts of HDL in the blood and has a protective feature of HDL against oxidation. Telomerase is reverse transcriptase enzyme that synthesizes and protects telomeres. Telomere length becomes shorter due to stress, obesity, and lack of exercise. In this study, paraoxonase1, telomerase enzymes and HDL values in blood serum of obese and non-obese cats were measured and their relationships with each other were evaluated. Body fat ratio in cats with body fat measurement system, those above 30% were evaluated as obese, and those below 30% were evaluated as the control group. Paraoxonase1 (p&amp;lt;0.001), telomerase (p&amp;lt;0.001) and HDL (p&amp;lt;0.008) values showed a statistically significant difference between the both groups, it was found to be lower in the obese group compared to the control group. As a result; paraoxonase1 and telomerase enzymes which are parameters of oxidative stress and are known to decrease in inflammation, were also found to be decreased in obese cats. The fact that HDL values are lower than the control group is an indicator that there are diseases that occur together with obesity.

SERUM LEVELS OF OXIDATIVE STRESS MARKERS IN SUBCLINICAL AND OVERT HYPOTHYROIDISM VERSUS CONTROL GROUP IN POPULATION OF KUTAHYA CITY, TURKEY

Background: Overproduction of oxygen-related free radicals and inadequate antioxidant defense are critical in hypothyroidism, as they might lead to future life-threatening diseases. The objectives of this study were to compare serum levels of oxidative stress markers; total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), paraoxonase-1 (PON-1), and arylesterase (ARYL) in patients with subclinical hypothyroidism (SH) and overt hypothyroidism (OH) versus healthy controls in population of Kutahya city, Turkey.Materials Methods: This cross-sectional study was conducted at Department of Biochemistry, Faculty of Medicine, Kutahya University of Health Sciences, Kutahya, Turkey, from July to December, 2016. Three study groups of 45 each were formed as healthy controls, patients with SH and OH. Serum levels of TOS, TAS, OSI, PON-1, and ARYL were five research variables with ratio scale, but skewed, so described by median and IQR with 95% Cl. Kruskal-Wallis and multiple comparison tests were used for hypotheses testing.Results: Serum levels of TOS and OSI were higher in SH group (p-values 0.032; .0001; respectively) and OH group (p-values .0001; .0001, respectively) than healthy controls, while serum levels of TAS, PON-1 and ARYL were lower in SH group (p-values .0001; .0001; .0001, respectively) and OH group (p-values .0001; .0001; .0001, respectively) than control group.Conclusion: Our study showed that serum levels of TOS and OSI were higher in subclinical and overt hypothyroidism than in healthy controls; while serum levels of TAS, PON-1, and ARYL were lower in subclinical and overt hypothyroidism than in healthy controls.

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.

Paraoxonase-1 Activity in Breast Cancer Patients Treated With Doxorubicin With or Without Trastuzumab

The objective of this study was to determine associations of paraoxonase-1 (PON-1) with development of cancer therapy-related cardiac dysfunction (CTRCD). PON-1 is a cardioprotective enzyme associated with high-density lipoprotein that prevents oxidized low-density lipoprotein formation. Given the role of oxidative stress in doxorubicin-induced cardiotoxicity, PON-1 activity may have relevance for the prediction of CTRCD. In 225 patients with breast cancer receiving doxorubicin with or without trastuzumab, we quantified PON-1 activity through its paraoxonase (Pon) and arylesterase (Aryl) enzymatic activity at baseline, during, and after doxorubicin completion. Echocardiograms were performed at baseline, during therapy, and annually. CTRCD was defined as a decrease in left ventricular ejection fraction by≥10% from baseline to<50%. Associations between baseline biomarkers and clinical variables were determined using multivariable linear regression. Associations between changes in biomarker activity and time to CTRCD were evaluated using Cox regression. Pon was directly associated with Black race and inversely associated with Stage 2 cancer. Aryl was inversely associated with body mass index. After doxorubicin completion, activity levels of Pon and Aryl were significantly decreased (median ratio compared with baseline for Pon: 0.95 [Q1-Q3: 0.81-1.07, P< 0.001]; for Aryl: 0.97 [Q1-Q3: 0.85-1.08, P=0.010]). A total of 184 patients had an available quantitated echocardiogram at baseline and at least 1 follow-up visit. Increases from baseline in Pon at doxorubicin completion were independently associated with increased CTRCD risk (per 10% increase: hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05-1.39; P=0.007). Associations between increases in Aryl and CTRCD tended in the same direction but were of borderline statistical significance (HR: 1.17; 95%CI: 0.99-1.38; P=0.071). In patients with breast cancer treated with doxorubicin with or without trastuzumab, increases in the Pon enzymatic activity level of PON-1 were associated with increased CTRCD risk. PON-1 activity may be relevant to mechanistic risk prediction of cardiotoxicity with anthracyclines.

Sodium ozagrel and atorvastatin for type 2 diabetes patients with lacunar cerebral infarction.

BACKGROUNDThe main pathological factor of cerebral infarction is atherosclerosis, which is the pathological process of chronic inflammatory diseases such as vascular smooth muscle hyperplasia, inflammatory cell infiltration, extracellular matrix increase, and thrombosis. At present, the focus of clinical treatment is anti-platelet aggregation and improving blood status, and current research is limited to improving symptoms only.AIMTo observe the effect of sodium ozagrel and atorvastatin on type 2 diabetes patients with lacunar cerebral infarction.METHODSEighty-two patients with type 2 diabetes and lacunar cerebral infarction admitted to our hospital from January 2018 to February 2020 were equally categorized into two groups according to their treatment method. The control group was administered atorvastatin, and the observation group was administered sodium ozagrel combined with atorvastatin. The National Institutes of Health stroke scale (NIHSS) score, activities of daily living (ADL) score, blood glucose, lipid levels, inflammatory factors, high-mobility group box 1 (HMGB1) levels, paraoxonase-1 (PON-1) levels, erythrocyte sedimentation rate (ESR), and macrophage migration inhibitory factor (MIF) levels were recorded before and after treatment. The total effective rate and adverse reaction rate of the two groups were analyzed. RESULTSThe total effective rate of the observation group (94.00%) was significantly higher than that of the control group (80.00%) (χ2 = 3.998; P = 0.046). The blood glucose indexes, total cholesterol levels, triglyceride levels, low-density lipoprotein cholesterol levels, high-sensitivity C-reactive protein levels, interleukin-1β levels, tumor necrosis factor-α levels, HMGB1 Levels, ESR, MIF levels, platelet aggregation rates, and plasma viscosity of the two groups decreased after treatment; however, high-density lipoprotein cholesterol and PON-1 Levels increased after treatment. After treatment, the blood glucose indexes; blood lipid indexes; inflammatory factors; HMGB1, PON-1, and MIF levels; ESR; platelet aggregation rate; and plasma viscosity of the observation group were better than those of the control group (P < 0.05). After treatment, all patients in the observation group had higher ADL scores and lower NIHSS scores than those in the control group (P < 0.05).CONCLUSIONSodium ozagrel with atorvastatin can reduce inflammatory reactions; regulate ESR and HMGB1, PON-1, and MIF levels; control blood glucose and lipid indexes; and alleviate nerve injury without increasing adverse effects of atorvastatin alone.

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).

Gene polymorphisms associated with lipid metabolism disorders in young adults with risk of ­sudden cardiac death

Aim. To study the frequency of polymorphisms in genes associated with lipid metabolism disorders in young people with risk of sudden cardiac death, to identify the relationships between gene polymorphisms and risk factors of sudden cardiac death, and to develop mathematical models to identify the probability of carrying mutations in these genes.&#x0D; Methods. The study included 436 young people (mean age 19.81.6 years). A standard examination and survey by questionnaire specially developed by us were conducted to identify an increased risk of sudden cardiac death. 59 individuals with a risk of sudden cardiac death were selected. The control group was 65 people, which was comparable to the study group. A blood test was performed to determine lipid profile and polymorphisms: Leu28Pro (rs 429358) in gene APOE, C3238G (rs 5128) in gene APOC3, Gln192Arg (rs 662) in gene PON1, Ser447Ter (rs 328) in gene LPL, G250A (rs 1800588) in gene LIPC. Statistical analysis was performed using the statistical package SPSS 17.0 and Statistica 6.0. The parametric KruskalWallis test, the MannWhitney U-test, the Pearsons chi-squared test, the Spearman rank correlation coefficient, and logistic regression analysis were used.&#x0D; Results. We revealed a high frequency of Gln192Arg (rs 662) polymorphism in the PON1 gene in the group of individuals at risk of sudden cardiac death and its correlation with the deaths in relatives under age 50 years. Mathematical models for predicting the presence of polymorphisms in genes associated with lipid metabolism disorders have been developed. Among the developed mathematical models, the models for identifying carriers of the minor allele of Gln192Arg polymorphism in the PON1 gene, Ser447Ter in the LPL gene, and 250 GA in the LIPC gene had the highest sensitivity, specificity, and accuracy.&#x0D; Conclusion. In persons at risk for sudden cardiac death, it is advisable to conduct a screening for mutations in genes associated with lipid metabolism disorders, especially in Gln192Arg polymorphism in gene PON1.

Antioxidant status in hypertensive disorders of pregnancy

ABSTRACT Objective: Pregnancy can be associated with maternal hypertension leading to possible complications in pregnancy outcome. Antioxidant status may be proned to changes during pregnancy with hypertension. The aim of our study was to estimate antioxidant status through high-risk pregnancies. Methods: Seventy-nine pregnant women with high-risk for preeclampsia development were included and 46 of them developed some hypertensive disorder in pregnancy. Superoxide-dismutase (SOD) and paraoxonase 1 (PON1) activities and relative proportion of PON1 activiity on different HDL subclasses were determined in 1st, 2nd, and 3rd trimester and prior to delivery. Results: SOD activity was significantly lower in 2nd and 3rd trimesters when compared to 1st trimester (P˂0.001) whereas PON1 activity was significantly higher in 3rd than in 1st trimester (P˂0.05) in group of hypertensive women. This group had significantly higher SOD and PON1 activities and relative proportion of PON1 on HDL3c subclasses in the 1st trimester, significantly increased PON1 in the 3rd trimester and prior to delivery and significantly higher PON1 activity on HDL3c subclasses (P˂0.05) than nonhypertensive group. In 1st trimester and prior to delivery, total PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant ability to mark out hypertension in pregnancy (P˂0.05). Conclusions: SOD activity decreased whereas total PON1 activity increased during pregnancy with hypertension. Pregnant women with hypertension had higher activities of PON1 and SOD and relative proportion of PON1 on HDL3c subclasses than nonhypertensive ones. PON1 activity and relative proportion of PON1 on HDL3c subclasses exhibited significant association with hypertension in pregnancy.

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.

Arylesterase activity of paraoxonase 1 in patients with primary hypertension

Abstract Introduction Paraoxonase 1 is an enzyme associated with high-density lipoprotein fraction and is considered to present antioxidant activity. Objectives The aim of the study was to assess the arylesterase activity of paraoxonase 1 (PON1) in the serum of patients with hypertension, due to effect of therapy and before treatment. Patients and Methods. The study was conducted in 76 patients with primary hypertension and 28 volunteers for the control group. Hypertensive subjects were assigned to one of three groups: well controlled (n=25), poorly controlled (n=26), and newly diagnosed before therapy (n=25) hypertension. We evaluated metabolic parameters in all participants using routine laboratory methods, as well as arylesterase activity of PON1. Results The four study groups differed with arylesterase activity of PON1 and the highest levels were found in patients with well controlled hypertension and the lowest in newly diagnosed. All patients diagnosed with hypertension presented negative correlations between PON1 and systolic and diastolic blood pressure. Conclusions Effective treatment of hypertension could result in increased PON1 activity, despite unfavorable homocysteine concentrations in blood. Untreated hypertension might decrease activity of PON.