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Oxidized low-density lipoproteins (ox-LDLs) are involved in atherosclerotic plaque formation and progression and have been linked to insulin resistance (IR). Myeloperoxidase is a potent oxidant of lipoproteins related to atherogenic risk. High-density lipoproteins (HDLs) are considered antioxidants due to their association with paraoxonase 1 (PON1). However, HDL can also be oxidized (ox-HDL), and its relationship with IR has not been described. This study evaluated the relationship between circulating levels of myeloperoxidase and paraoxonase 1, diet, and serum levels of ox-LDL and ox-HDL in young people with IR. This cross-sectional study examined 136 young subjects (67 and 69 with and without insulin resistance, respectively). Serum levels of ox-LDL, ox-HDL, myeloperoxidase, and PON1 were quantified using an enzyme-linked immunosorbent assay. The nutritional dietary content of the foods was determined with a food frequency questionnaire, which was analyzed with Nutrimind 2013 software. Serum ox-HDL levels were higher in young subjects without IR than those with IR (p = 0.031). Women with IR presented increased ox-LDL levels compared with women without IR (p = 0.012) and men with IR (p < 0.001). In the IR group, serum ox-LDL levels were negatively correlated with total cholesterol, triglycerides, and LDL-C, whereas the correlation was positive in the insulin-sensitive group. Consumption of vitamins B1 and B2 was related to increased HDL-C levels, while higher ox-LDL levels were related to vitamin K intake. In addition, low energy consumption and phosphorus increased PON1 levels. The results suggest that insulin resistance in young women may promote lipoprotein oxidation, and the intake of B complex vitamins may have an antiatherogenic effect. [ABSTRACT FROM AUTHOR]

Background and Objectives: Atherosclerosis, driven by dyslipidaemia and oxidative stress, is a leading cause of cardiovascular morbidity and mortality. This study evaluates the effects of vigorous-intensity bodybuilding exercise (VIBBE) on atherosclerosis biomarkers—including paraoxonase-1 (PON1) and arylesterase (ARE) activities—and lipid profiles in male bodybuilders who do not use anabolic-androgenic steroids. Comparisons were made with individuals engaged in moderate-intensity aerobic exercise (MIAE), as well as overweight/obese sedentary (OOS) and normal-weight sedentary (NWS) individuals. Materials and Methods: A cross-sectional study was conducted involving 122 healthy male participants aged 18–45 years, divided into four groups: VIBBE (n = 31), OOS (n = 30), MIAE (n = 32), and NWS (n = 29). Anthropometric assessments were performed, and fasting blood samples were collected for biochemical analyses, including lipid profiles and PON1 and ARE activities. Statistical analyses compared the groups and evaluated correlations between adiposity measures and atherosclerosis biomarkers. Results: The VIBBE group exhibited significantly lower levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and logarithm of the TG to high-density lipoprotein cholesterol (HDL-C) ratio [log(TG/HDL-C)] compared to the OOS group (p < 0.05 for all), indicating improved lipid profiles. However, these improvements were not significant when compared to the NWS group (p > 0.05), suggesting that VIBBE may not provide additional lipid profile benefits beyond those associated with normal weight status. PON1 and ARE activities were significantly lower in the VIBBE group compared to the MIAE group (p < 0.05 for both), suggesting that VIBBE may not effectively enhance antioxidant defences. Correlation analyses revealed significant inverse relationships between PON1 and ARE activities and adiposity measures, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body fat percentage (BFP), fat mass index (FMI), and obesity degree (OD) (p < 0.05 for all). Positive correlations were observed between oxLDL and log(TG/HDL-C) and adiposity measures (p < 0.05 for all). Conclusions: Vigorous-intensity bodybuilding exercise improves certain lipid parameters compared to sedentary obese individuals but does not significantly enhance antioxidant enzyme activities or further improve lipid profiles beyond those observed in normal-weight sedentary men. Conversely, moderate-intensity aerobic exercise significantly enhances PON1 and ARE activities and improves lipid profiles, offering superior cardiovascular benefits. These findings underscore the importance of incorporating moderate-intensity aerobic exercise into physical activity guidelines to optimize cardiovascular health by balancing improvements in lipid metabolism with enhanced antioxidant defences. [ABSTRACT FROM AUTHOR]

Medical intervention in poisoning by organophosphate toxic agents (OPA) using atropine sulfate, 2-pyridinaldoxymethyl chloride (2-PAM), diazepam and other similar drugs can prevent the fatal outcome of poisoning. These drugs do not protect in case of sudden chemical attack and against post-exposure complications associated with permanent brain damage. The U.S. Department of Defense is funding research that can significantly simplify the protection of military personnel from OPA damage in the future. Their essence is in the use of gene therapy technologies, which allow experimental animals to produce their own proteins that destroy OPA and provide them with protection for several months. The aim of the work is to identify the achieved level of knowledge in the research using gene therapy technologies to create living objects resistant to OPA. The research method is analytical. The source base of the research are publications in scientific journals and descriptions of patents. Discussion of the results. As an enzyme that breaks down OPA in such experiments, genetically modified paraoxanase 1 (PON1) showed the greatest efficiency. PON1 hydrolyzes G-type OPAs, paraoxone, chlorpyrifosoxone, diazoxone and several other organophosphates. Adenoassociated virus vectors (AAV8, etc.) were used to introduce the gene encoding PON1 into the animal's body. A single injection of AAV8 carrying the recombinant PON1-IF11 gene (AAV8-PON1-IF11) resulted in high expression and secretion of the recombinant PON1-IF11 protein into the bloodstream and provided asymptomatic protection against multiple lethal doses of G-type OPA for at least 5 months. These studies are still in their early stage. An analysis of the affiliation of the authors of publications and patents showed a high involvement of the U.S. military department and its cooperating organizations (DTRA, etc.) in such research. Conclusion. Given the fascination in the West with the ideas of human modification using gene therapy methods, this direction will be intensively developed for military purposes. At the same time, the idea of pre-created resistance to OPA is in demand by the widespread use of organophosphates in agriculture. The author believes that it would be safer to use allogeneic mesenchymal stem cells transfected with genetically modified PON1 variants with enhanced enzyme activity. This resistance to OP agents can be health protective and lifesaving in soldiers in real combat when the enemy uses these agents. However, this approach must be based on a strong experimental background. The door is open, the technologies are available.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) or end stage renal disease (ESRD) are at increased risk of atherosclerosis and cardiovascular event. Paraoxonase 1 has atheroprotective effects through its role in lipid peroxidation. Objectives: This study aimed to check serum paraoxonase 1 level and gene polymorphism (PON 1- Q192R) as an atherosclerotic marker in CKD patients in Menoufia University Hospitals, Egypt. Patients and methods: This case-control study included 65 patients with CKD attending Menoufia University Hospitals. Patients were classified into 2 groups: 30 patients on conservative therapy (Group II) and 35 ESRD patients on regular hemodialysis (HD) more than 6 months (Group III). Thirty healthy age- and gender-matched individuals were evaluated as control group (group I). Complete blood count, lipid profile, blood urea, serum creatinine, C-reactive protein, serum homocysteine and PON1 lactonase activity (human serum paraoxonase 1) were measured using commercially available enzyme-linked immunosorbent assay kits and genetic study (PON 1-Q192R) was determined by Real time polymerase chain reaction (PCR). Carotid intima media thickness (CIMT) was measured through ultrasonographic examination of carotid arteries. Results: CIMT was significantly higher in CKD patients than in control group. Serum PON 1 was significantly lower in ESRD patients on HD than in CKD patients predialysis, which in turn was significantly lower than in healthy control subject. There was statistical significant negative correlation between CIMT and PON 1 level. There was statistically significant difference between patients and control as regards paraoxonase gene polymorphism. Genotype QQ and Q allele were common in CKD & ESRD patients than in control. Conclusion: Serum paraoxonase 1 level may be a potential biomarker of atherosclerosis in CKD patients. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case–control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor—CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29–16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23–7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01–1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07–0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05–0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD. [ABSTRACT FROM AUTHOR]

• CPB leads to inflammatory responses and oxidative stress. • PON1 is decreased in systemic inflammation and ischemia, like that during CPB is. • Glucocorticoids counteract oxidative stress by up regulating PON1 gene expression. • Methylprednisolone doesn't have significant effects on PON1 activity during CPB. Cardiopulmonary bypass (CPB) is linked to systemic inflammatory responses and oxidative stress. Paraoxonase 1 (PON1) is an antioxidant enzyme with a cardioprotective role whose activity is decreased in systemic inflammation and in patients with acute myocardial and global ischemia. Glucocorticoids counteract the effect of oxidative stress by upregulating PON1 gene expression. The authors aimed to determine the effect of methylprednisolone on PON1 activity during cardiac surgery on CPB. Prospective, randomized, controlled clinical trial. The University Medical Center Ljubljana, Slovenia. Forty adult patients who underwent complex cardiac surgery on CPB between February 2016 and December 2017 were randomized into methylprednisolone and control groups (n = 20 each). Patients in the methylprednisolone group received 1 g of methylprednisolone in the CPB priming solution, whereas patients in the control group were not given methylprednisolone during CPB. The effect of methylprednisolone from the CPB priming solution was compared with standard care during CPB on PON1 activity until postoperative day 5. Correlations of PON1 activity with lipid status, mediators of inflammation, and hemodynamics were analyzed also. No significant differences were found between study groups for PON1 activity, high-density lipoprotein, and low-density lipoprotein in any of the measurement intervals (p > 0.016). The methylprednisolone group had significantly lower tumor necrosis factor alpha (p < 0.001) and interleukin-6 (p < 0.001), as well as C-reactive protein and procalcitonin (p < 0.016) after surgery. No significant difference was found between groups for hemodynamic parameters. A positive correlation existed between PON1 and lipid status, whereas a negative correlation was found between PON1 activity and tumor necrosis factor alpha, interleukin-6, and CPB duration. Methylprednisolone does not influence PON1 activity during cardiac surgery on CPB. [ABSTRACT FROM AUTHOR]

Cognitive impairment is one of the main complications of diabetes and patients with cognitive impairment are considered to be in an intermediate stage of decreased cognition with higher risk of developing dementia and Alzheimer's disease. This study aimed at evaluating serum activity of two esterase enzymes including cholinesterase and paraoxonase 1 (PON 1) in diabetic patients and association with cognitive performance and metabolic parameters. In this crosssectional study, 128 diabetic patients were enrolled. Cognitive performance was evaluated using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Body mass index, fasting blood glucose, fasting blood insulin, insulin resistance, serum cholinesterase and paraoxonase 1 activity were measured. Prevalence of cognitive impairment was found to be 77% in the study population. Serum cholinesterase activity was found to be higher in diabetic patients with cognitive impairment than the patients with normal cognitive performance (p < 0.04). Further, a negative correlation was found between cognitive performance and cholinesterase activity, albeit statistically non-significant. Alteration in the activity of cholinesterase enzyme was shown to be associated with cognitive impairment in diabetic patients and future studies are required to find the pathophysiological mechanisms of diabetic cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background and Objectives: Atherosclerosis, driven by dyslipidaemia and oxidative stress, is a leading cause of cardiovascular morbidity and mortality. This study evaluates the effects of vigorous-intensity bodybuilding exercise (VIBBE) on atherosclerosis biomarkers—including paraoxonase-1 (PON1) and arylesterase (ARE) activities—and lipid profiles in male bodybuilders who do not use anabolic-androgenic steroids. Comparisons were made with individuals engaged in moderate-intensity aerobic exercise (MIAE), as well as overweight/obese sedentary (OOS) and normal-weight sedentary (NWS) individuals. Materials and Methods: A cross-sectional study was conducted involving 122 healthy male participants aged 18–45 years, divided into four groups: VIBBE (n = 31), OOS (n = 30), MIAE (n = 32), and NWS (n = 29). Anthropometric assessments were performed, and fasting blood samples were collected for biochemical analyses, including lipid profiles and PON1 and ARE activities. Statistical analyses compared the groups and evaluated correlations between adiposity measures and atherosclerosis biomarkers. Results: The VIBBE group exhibited significantly lower levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and logarithm of the TG to high-density lipoprotein cholesterol (HDL-C) ratio [log(TG/HDL-C)] compared to the OOS group (p < 0.05 for all), indicating improved lipid profiles. However, these improvements were not significant when compared to the NWS group (p > 0.05), suggesting that VIBBE may not provide additional lipid profile benefits beyond those associated with normal weight status. PON1 and ARE activities were significantly lower in the VIBBE group compared to the MIAE group (p < 0.05 for both), suggesting that VIBBE may not effectively enhance antioxidant defences. Correlation analyses revealed significant inverse relationships between PON1 and ARE activities and adiposity measures, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body fat percentage (BFP), fat mass index (FMI), and obesity degree (OD) (p < 0.05 for all). Positive correlations were observed between oxLDL and log(TG/HDL-C) and adiposity measures (p < 0.05 for all). Conclusions: Vigorous-intensity bodybuilding exercise improves certain lipid parameters compared to sedentary obese individuals but does not significantly enhance antioxidant enzyme activities or further improve lipid profiles beyond those observed in normal-weight sedentary men. Conversely, moderate-intensity aerobic exercise significantly enhances PON1 and ARE activities and improves lipid profiles, offering superior cardiovascular benefits. These findings underscore the importance of incorporating moderate-intensity aerobic exercise into physical activity guidelines to optimize cardiovascular health by balancing improvements in lipid metabolism with enhanced antioxidant defences.

Abstract Background Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. Methods This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. Results Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. Conclusions Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.

Introduction: Paraoxonase 1 (PON1) is the enzyme that removes carcinogenic radicals from lipids. The aim of the study was to investigate the differences in PON1 activity and oxidation stress parameters between patients with cervical intraepithelial neoplasia (CIN) and healthy controls. Materials and methods: The study included 65 women with CIN and 109 healthy women. Lipid parameters were determined on Cobas Integra 400 plus (Roche, Mannheim, Germany). Tiols and reduced glutathione (GSH) were determined spectrophotometric using Eliman reagent. Activity of PON1 was assessed with two substrates, paraoxon and phenylacetate by spectrophotometric method. Malondialdehyde (MDA) was determined by high performance liquid chromatography (Shimadzu Corporation, Kyoto, Japan). Mann-Whitney-test, t-test, χ²-test, correlation and logistic regression was used in statistical analysis. P < 0.05 was considered statistically significant. Results: The basal (P = 0.929) and NaCl-stimulated (P = 0.985) PON1 activity and activities standardised on the concentration of high-density lipoprotein (HDL; P = 0.076; P = 0.065, respectively) and apolipoprotein AI (apo AI; P = 0.444; P = 0.499, respectively) as well as PON1 phenotypes (P = 0.842) did not differ significantly between the groups. The PON1 arylesterase activity (53±19 kU/L vs. 77±17 kU/L; P < 0.001) and HDL-standardized activity (37 (28-44) kU/mmol vs. 43 (37-50) kU/mmol; P < 0.001) and apoAI (29±11 kU/g vs. 44±11 kU/g; P < 0.001) was significantly reduced in the CIN group. The concentration of the thiol groups was similar (P = 0.519), of MDA was lower (0.39 (0.27-0.55) µmol/L vs. 0.76 (0.57-1.15) µmol/L; P < 0.001) and of GSH was higher (112.0 (66.0-129.6) µg/mL vs. 53.4 (34.8-134.4) µg/mL; P < 0.001) in the CIN group. Conclusion: Reduced PON1 arylesterase activity, lower MDA and higher GSH concentration were observed in CIN patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationships between serum levels of paraoxonase-1 (PON-1) and interleu‑ kin-17A (IL-17A) and the degree of neurological impairment and short-term prognosis in acute ischemic stroke (AIS) . Methods Totally 132 AIS patients (AIS group) and 52 healthy volunteers (control group) were selected. According to the National Institutes of Health Stroke Scale (NIHSS) score, AIS patients were divided into the mild group (42 cases), moderate group (53 cases), and severe group (37 cases) ；according to the modified Rankin Scale (mRS) score on the 90 d of onset, AIS patients were divided into the poor prognosis group (39 cases) and good prognosis group (93 cases) . Se‑ rum PON-1 and IL-17A levels were detected and clinical data were collected. Multivariate Logistic regression analysis was used to analyze the factors affecting the short-term prognosis of AIS patients. The value of PON-1 and IL-17A in predicting short-term prognosis of AIS patients was analyzed by receiver operating characteristic (ROC) curve. Results The serum PON-1 level in the AIS group was lower than that in the control group (P<0. 05), and IL-17A level was higher than that in the control group (P<0. 05) . Serum PON-1 level was lower in the severe group than in the mild and moderate groups (both P<0. 05), and IL-17A level was higher than those in the mild and moderate groups (both P<0. 05) . The level of serum PON-1 in the poor prognosis group was lower than that in the good prognosis group (P<0. 05), and the level of IL-17A was higher than that in the good prognosis group (P<0. 05) . High NIHSS score and high level of IL-17A at admission were risk factors for poor short-term prognosis in AIS patients (both P<0. 05), and high level of PON-1 was protective factor (P<0. 05) . The AUC of PON-1 and IL-17A in predicting the short-term prognosis of AIS patients was 0. 798 and 0. 795, and the AUC of them combined was 0. 953, which was higher than that of either alone (both P<0. 05) . Conclusion Serum PON-1 level decreases and IL-17A level increases in AIS patients, which is associated with the aggravation of nerve defect and poor short-term prognosis, and can be used as indicators for short-term prognosis of AIS patients. [ABSTRACT FROM AUTHOR]

Expression of recombinant paraoxonase 1 (PON1) in the human embryonic kidney (HEK293F) cell line was evaluated. Two recombinant human PON1 proteins were investigated: PON1-Fc, which has an Fc-tag on its C-terminal, and His-PON1-Fc, which has an Fc-tag on its C-terminal and histidine on its N-terminal. The influence of high and low-density lipoproteins, copper ions, iron ions, and thiolactone homocysteine, on arylesterase and lactonase activities of PON1 in human serum was examined. Two activities of PON1, arylesterase and lactonase, were measured using earlier elaborated kinetic spectrophotometric method with temperature control at 37°C using the water thermostated cuvette holder. It was demonstrated that the HEK293F expression platform is useful for obtaining recombinant human PON1 protein. Also, addition of high-density lipoprotein increased serum arylesterase and lactonase activity of PON1 to a greater extent than the addition of PON1-Fc or HisPON1-Fc recombinant proteins. In contrast, the addition of high-density lipoprotein to samples containing PON1-Fc or His-PON1-Fc did not increase PON1 activities, while low-density lipoprotein, copper ions, and iron ions, depressed PON1 arylesterase and lactonase activity. Obtained results indicated that it may be advantageous to stimulate PON1 activities rather than supplement with endogenous PON1 protein and HDL, which could be an interesting direction for further study. Furthermore, the work has highlighted some potential research directions for the use of PON1 as a therapeutic molecules. Nevertheless, the study had some limitations and should therefore be treated as a preliminary study.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

It is known that oxidative stress originating from reactive oxygen species plays a role in the pathogenesis of Alzheimer's disease. In this study, the role of antioxidant status associated with oxidative stress in Alzheimer's disease was investigated. Peripheral blood samples were obtained from 28 healthy individuals (as control) and 28 Alzheimer's patients who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Catalase, glutathione S‐transferase and paraoxonase 1 enzyme activities in blood plasma and glutathione S‐transferase enzyme activities in erythrocytes were determined by spectrophotometer. Catalase, glutathione S‐transferase and presenilin 1 gene expressions in leukocytes were determined using qRT‐PCR. Data were analysed with SPSS one‐way anova, a LSD post hoc test at p < 0.05. The activity of each enzyme was significantly reduced in Alzheimer's patients compared to control. The catalase gene expression level did not change compared to the control. Glutathione S‐transferase and presenilin 1 gene expression levels were increased compared to the control. [ABSTRACT FROM AUTHOR]

Background: Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART. Methods: This prospective nested case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed. Results: Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups. Conclusions: Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases. [ABSTRACT FROM AUTHOR]

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 43 kDa. 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 ± 2.14 μM, Ki values between 8.58 ± 0.36 and 111 ± 1.27 μM. The drugs with the strongest inhibitory effect were nisoldipine with 13.987 ± 0.59 μM and nicardipine with 20.158 ± 0.43 μM. 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. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) may cause premature development of some diseases. PON1 genes may be involved in the pathogenesis of MetS. The aim of study was to evaluate the association between Q192R and L55M gene polymorphisms and its enzyme activity with the MetS components in subjects with and without MetS. Polymerase Chain Reaction and Restriction Fragment Length Polymorphism analysis were performed to determine polymorphisms of the paraoxonase1 gene in subjects with and without metabolic syndrome. Biochemical parameters were measured by spectrophotometer. The MM, LM, and LL genotype frequencies of the PON1 L55M polymorphism were 10.5, 43.4, and 46.1%, and 22.4, 46.6, and 31% and; the QQ, QR, and RR genotype frequencies of the PON1 Q192R polymorphism were 55.4, 38.6 and 6%; and 56.5, 34.8 and 8.7% in subjects with and without MetS, respectively. The L and M allele frequencies were 68 and 53%; and 32 and 47% for PON1 L55M in subjects with and without MetS, respectively. The Q and R allele frequencies for PON1 Q192R were 74 and 26% in both groups. There were significant differences in HDL-cholesterol level and PON1 activity in the genotypes QQ, QR, and RR of the PON1 Q192R polymorphism in subjects with MetS. The PON1 Q192R genotypes had only effected on PON1 activity and HDL-cholesterol level in subjects with MetS. Different genotypes of the PON1 Q192R seem to be important candidates to make the subjects susceptible to MetS in the Fars ethnic group. [ABSTRACT FROM AUTHOR]

الملخص: أهداف البحث: إن مصل باراوكسوناز هو بروتين سكري، مع أنشطة مضادة للتأكسد ومضادة لتصلب الشرايين. يعتبر تعدد الأشكال الجيني غلوتامين192أرجينين وتعدد الأشكال الجيني ليوسين55 مثيونين لمصل باراوكسوناز أحد عوامل الخطر لمرض الشريان التاجي، وهو أقل استكشافا في الهنود الجنوبيين. كنا نهدف إلى تحديد تعدد الأشكال الجيني غلوتامين192أرجينين و تعدد الأشكال الجيني ليوسين55مثيونين لمصل باراوكسوناز في مرضى مرض الشريان التاجي وتقييم النمط الجيني وترددات الأليل لتعدد الأشكال الجيني في مصل باراوكسوناز 1. طرق البحث: تضمنت هذه الدراسة الاستباقية وضبط الحالات 20 شخصا في كل مجموعة مع مرضى مرض الشريان التاجي مثبتين في تصوير الأوعية الدموية في مجموعة الحالة. تم قياس نشاط مصل باراوكسوناز 1 وتم تحديد تعدد الأشكال الجيني لمصل باراوكسوناز. تم تحليل مصل مصل باراوكسوناز كميا باستخدام مختصر مقايسة الممتز المناعي المرتبط بالإنزيم لمصل باراوكسوناز التابع لشركة راي بايو. تم استخدام اختبار مربع كاي لمعرفة ارتباط الأنماط الجينية بالجنس، وأي أمراض مصاحبة في الحالات والضوابط. النتائج: كان النوع المتحور من تعدد الأشكال ليوسين55مثيونين شائعا في 50٪ من المرضى الذين أظهروه بينما في غلوتامين192أرجينين أظهر 42.5٪ من المشاركين النمط السوي. لم تظهر قيم مصل باراوكسوناز المتوسطة بين المجموعتين فرقا إحصائيا بينما أظهرت أنشطة مصل باراوكسوناز فرقا إحصائيا بين المجموعتين بقيم أقل في مجموعة الحالة. لم يكن فرق النوع المتحور من تعدد الأشكال ليوسين55مثيونين ذو دلالة إحصائية بين الحالة ومجموعات التحكم بينما كان النوع المتحور من تعدد الأشكال غلوتامين192أرجينين ذو دلالة إحصائية في الحالات مقارنة بالمجموعة الضابطة. الاستنتاجات: لوحظ انخفاض مستويات مصل باراوكسوناز 1 والبروتين الشحمي المرتفع الكثافة في البلازما، وارتفاع البروتين الشحمي المنخفض الكثافة، وإجمالي مستويات الكوليسترول والدهون الثلاثية في مرضى مرض الشريان التاجي. لوحظ أن النوع المتحور من تعدد الأشكال غلوتامين192أرجينين أعلى في مرضى مرض الشريان التاجي مقارنة بالأفراد الأصحاء. Abstract: Objectives: Serum paraoxonase (PON) is a glycoprotein with antioxidant and anti-atherosclerotic activities. The Q192R and L55M gene polymorphisms of PON have been implicated as risk factors for coronary artery disease (CAD) but have not been extensively explored in South Indians. We aimed to assess the Q192R and L55M genetic polymorphisms of the PON1 gene in participants with CAD, including genotypes and allele frequencies for PON1 gene polymorphism. Methods: This prospective case-control study involved 20 participants in each group. Patients with angiographically demonstrated CAD were included in the case group. PON1 activity was measured, and PON gene polymorphism was determined. Serum PON was quantitatively analyzed with a RayBio® Human PON1 ELISA kit. Chi square tests were used to assess the association of the genotypes with sex and any comorbidities in cases and controls. A p value ≤ 0.05 was considered significant. Results: Mutant type L55M polymorphism was observed in 50% of patients, whereas wild type Q192R polymorphism was observed in 42.5% of the participants. The mean PON values between groups did not significantly differ, whereas PON U/L was significantly (p = 0.001) lower in the case group. The L55M polymorphism did not significantly differ between the case and the control groups (p = 0.213), whereas the Q192R polymorphism was statistically significant in cases compared with controls (p ≤ 0.001) Conclusion: Low plasma PON1 and HDL levels, and higher LDL, total cholesterol and triglyceride levels were observed in patients with CAD. More patients with CAD than healthy individuals had Q192R polymorphism.

Vitamin E and paraoxonase 1 (PON1) are associated with cancer development. However, their interactive effect on colorectal cancer (CRC) risk is inconclusive. We conducted a case–control study including 1,351 CRC patients and 2,670 controls at the Korean National Cancer Centre (KNCC). There was an inverse association between vitamin E intake and CRC risk (odds ratio (OR) = 0.31; 95% confidence interval (CI) = 0.22–0.42). We identified a reduced CRC risk among individuals with CC genotype of PON1 rs662 polymorphism compared with subjects carrying the T allele (OR = 0.74; 95% CI = 0.61–0.90). The highest interaction between vitamin E intake and PON1 rs662 variants was significant for the subjects carrying the CC genotype (p-interaction = 0.014). This study provided further supporting evidence that vitamin E intake is associated with lower odds of CRC. Furthermore, the activity of vitamin E is strengthened among individuals carrying C allele of the PON1 rs662 polymorphism. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) exhibits cardio- and neuro-protective properties, which are thought to be promoted by paraoxonase 1 (PON1), a hydrolytic enzyme associated with an HDL subfraction also enriched with an anticoagulant protein (PROS1) and amyloid beta-transport protein clusterin (CLU, APOJ). Reduced levels of PON1 activity, characterized biochemically by elevated levels of homocysteine (Hcy)-thiolactone, oxidized lipids, and proteins modified by these metabolites in humans and mice, are associated with pathological abnormalities affecting the cardiovascular system (atherothrombosis) and the central nervous system (cognitive impairment, Alzheimer's disease). The molecular bases of these abnormalities have been largely unknown. Proteomic and metabolic studies over the past decade have significantly contributed to our understanding of PON1 function and the mechanisms by which PON1 deficiency can lead to disease. Recent studies discussed in this review highlight the involvement of dysregulated proteostasis in the pro-oxidative, pro-atherothrombotic, and pro-amyloidogenic phenotypes associated with low PON1 activity. [ABSTRACT FROM AUTHOR]

Expression of recombinant paraoxonase 1 (PON1) in the human embryonic kidney (HEK293F) cell line was evaluated. Two recombinant human PON1 proteins were investigated: PON1-Fc, which has an Fc-tag on its C-terminal, and His-PON1-Fc, which has an Fc-tag on its C-terminal and histidine on its N-terminal. The influence of high and low-density lipoproteins, copper ions, iron ions, and thiolactone homocysteine, on arylesterase and lactonase activities of PON1 in human serum was examined. Two activities of PON1, arylesterase and lactonase, were measured using an earlier elaborated kinetic spectrophotometric method with temperature control at 37°C using the water thermostated cuvette holder. It was demonstrated that the HEK293F expression platform is useful for obtaining recombinant human PON1 protein. Also, the addition of high-density lipoprotein increased serum arylesterase and lactonase activity of PON1 to a greater extent than the addition of PON1-Fc or HisPON1-Fc recombinant proteins. In contrast, the addition of high-density lipoprotein to samples containing PON1-Fc or His-PON1-Fc did not increase PON1 activities, while low-density lipoprotein, copper ions, and iron ions, depressed PON1 arylesterase and lactonase activity. Obtained results indicated that it may be advantageous to stimulate PON1 activities rather than supplement with endogenous PON1 protein and HDL, which could be an interesting direction for further study. Furthermore, the work has highlighted some potential research directions for the use of PON1 as a therapeutic molecule. Nevertheless, the study had some limitations and should therefore be treated as a preliminary study. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is an autoimmune disease of the thyroid gland. Free radicals have been reported to be responsible for the complications observed in the pathogenesis of thyroid diseases and the later stages of the disease. Myeloperoxidase (MPO), which is released from neutrophils during inflammation and oxidative stress and causes cell destruction, is a marker that plays a role in the development of cardiovascular disease associated with oxidative damage in the arterial wall. Paraoxonase-1(PON-1), which is one of the molecules that play a role in oxidant balance, is an enzyme that inhibits lipoprotein oxidation by hydrolyzing lipid peroxides in oxidized low-density lipoprotein(LDL) structure. We investigated the role of HDL-associated MPO and PON-1 in patients with HT in terms of coronary artery disease. Our study group consisted of 54 patients with Hashimoto's diagnosis and 50 healthy individuals in the control group.MPO and PON-1 levels were determined spectrophotometrically. When the study groups were evaluated, MPO levels were significantly higher in patients with Hashimoto thyroiditis than in the control group (p < 0.05, p = 0.001). A negative correlation was obtained between MPO and PON-1 (r = − 0.685). The decrease in PON-1 activity and increase in MPO activity due to the hypothyroid effect increases lipid peroxide formation and accelerates oxidized LDL formation, which leads to a decrease in antioxidant capacity and the development of atherosclerosis. Since oxidative stress in thyroid diseases is also responsible for the complications observed in the later stages of the disease, we think that important data were obtained with this study in terms of both diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Childhood obesity presents numerous comorbidities such as insulin resistance (IR) and dyslipidemia, and could be associated with alterations in novel markers of cardiovascular (CV) risk like: (1) the activities of associated enzymes such as lipoprotein associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON 1), (2) reverse cholesterol transport (RCT), which comprises cellular cholesterol efflux (CCE), in addition to lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities, and (3) high density lipoprotein (HDL) antioxidant capacity. Moreover, IR could worsen these cardiometabolic alterations. The objective of the present study was to characterize the effect of IR on novel CV markers in a pediatric population with obesity.Twenty-five obese children and adolescents with IR, and 25 without IR took part in the study. Anthropometric parameters, Tanner stage and dietary habits were registered. Glucose, insulin, non-esterified fatty acid (NEFA), lipid, and high sensitivity C reactive protein (hsCRP) levels, plus Lp-PLA2, LCAT, CETP and PON 1 activities, as well as CCE and HDL antioxidant capacity were measured. A cutoff point of 3.16 in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) determined the presence of IR.No differences were observed in age, sex and Tanner stage. Expectedly, the group with IR displayed higher insulin and NEFA levels (p < 0.05). They also presented increased Lp-PLA2 and decreased PON activities (p < 0.05). Importantly, these differences were associated with dietary habits (p < 0.05).IR present in pediatric obesity associated with vascular specific inflammation and reduced PON 1 activity, in addition to alterations in glucose metabolism, thus increasing CV risk in adulthood. These proatherogenic disturbances were conditioned by dietary habits. [ABSTRACT FROM AUTHOR]

Background: A further understanding of the mechanisms linking inflammation to T2D and related complications can help prevent or control this silent but dangerous disease. This study was conducted to determine the association between paraoxonase 1 (PON1) activity and interleukin-6 (IL-6) in type 2 diabetes (T2D). Furthermore, we have evaluated the role of age and gender in the relationship between the PON1 activity and IL-6. Methods: A total of 105 people with T2D were enrolled in this study. IL-6 levels were determined using ELISA. For the PON1 activity assay, the hydrolysis rate of the substrate phenylacetate was spectrophotometrically assayed in serum at 270 nm. The determined velocities were the initial velocities of substrate hydrolysis. Results: PON1 activity was negatively correlated with IL-6 in total data (r = -0.34, P = 0.001). In both groups with age ≥50 and <50 years, PON1 activity was negatively correlated with IL-6, but the correlation was significant in patients aged 50 years and above (r = -0.358, P = 0.005) compared with patients with age <50 years. In both women and men, PON1 activity was negatively correlated with IL-6, but the correlation was significant in women (r = -0.318, P = 0.006) in comparison with men. Conclusions: Inverse association between PON1 activity and IL-6 in T2D may represent the oxidative-inflammatory interaction in this disease. Our findings highlight that at older ages and in women, the associations between lower PON1 activity and higher IL-6 concentrations are more evident, and this should be considered in patients with T2D. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD), which often progresses to PD dementia. PD patients with and without dementia may differ in certain biochemical parameters, which could thus be used as biomarkers for PD dementia. The enzyme paraoxonase 1 (PON1) has previously been investigated as a potential biomarker in the context of other types of dementia. In a cohort of PD patients, we compared a group of 89 patients with cognitive impairment with a group of 118 patients with normal cognition. We determined the kinetic parameters Km and Vmax for PON1 for the reaction with dihydrocoumarin and the genotype of four single nucleotide polymorphisms in PON1. We found that no genotype or kinetic parameter correlated significantly with cognitive impairment in PD patients. However, we observed associations between PON1 rs662 and PON1 Km (p < 10−10), between PON1 rs662 and PON1 Vmax (p = 9.33 × 10−7), and between PON1 rs705379 and PON1 Vmax (p = 2.21 × 10−10). The present study is novel in three main aspects. (1) It is the first study to investigate associations between the PON1 genotype and enzyme kinetics in a large number of subjects. (2) It is the first study to report kinetic parameters of PON1 in a large number of subjects and to use time-concentration progress curves instead of initial velocities to determine Km and Vmax in a clinical context. (3) It is also the first study to calculate enzyme-kinetic parameters in a clinical context with a new algorithm for data point removal from progress curves, dubbed iFIT. Although our results suggest that in the context of PD, there is no clinically useful correlation between cognitive status on the one hand and PON1 genetic and enzyme-kinetic parameters on the other hand, this should not discourage future investigation into PON1's potential associations with other types of dementia. [ABSTRACT FROM AUTHOR]

Paraoxonase 1 (PON1), an enzyme with multifactorial antioxidant activity, has a protective role against oxidative stress, which is supposed to contribute to the development of cancers including breast cancer. The aim of this study was to examine the correlation of PON1-L55M common genetic polymorphism with the risk of breast cancer in a meta-analysis approach which was followed by an in silico analysis. The eligible studies were collected from valid electronic databases such as Google Scholar, PubMed, Embase, and Web of Science. Quantitative synthesis was performed to report the strength of PON1-L55M polymorphism with breast cancer. Some bioinformatics tools were used to analyze the effects of L55M variation on PON1 gene function. The meta-analysis revealed that there are significant associations between the mentioned polymorphism and breast cancer in M vs. L, MM vs. LL, LM vs. LL, MM + LM vs. LL, and MM vs. LL + LM genetic models. Besides, similar results were observed in the stratified analyses based on ethnicity, genotyping method, Hardy-Weinberg equilibrium in control groups, and sample size. Bioinformatics analysis revealed that the PON1 could be damaging to the protein function. Our findings propose that the PON1-L55M genetic polymorphism might be a genetic risk factor for the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Background: PON1 is an High Density Lipoprotein (HDL)-associated esterase. Two common polymorphisms in the PON1 gene, Q192R and L55M substitutions, determine the inter-individual variation in PON1 activity. The association of these polymorphisms with the risk of ischemic stroke remains controversial. In the present study, the role of PON1 Q192R gene polymorphism in ischemic stroke was studied in the Indian population. Design and Methods: In the present case-control study, the PON1 Q192R gene polymorphism was screened in ischemic stroke patients (n: 63) and age, sex-matched controls (n: 63) using the Polymerase Chain Reaction-Restriction Segment Length Polymorphism (PCR-RFLP) method. Results: The mean age of stroke presentation was 58.11 ± 15.4 years. A total of 17.4% cases presented with young stroke (

Abstract Objective The aim of the present study was to examine the relation between the PON1 polymorphisms and recurrent pregnancy loss (RPL). Methods In a cross-sectional study, blood samples were collected from 100 females. DNA was extracted and PON1 genotypes were determined by polymerase chain reaction (PCR) amplification. Results Regarding PON1 L55M, the mutated allele (M) frequency was found in 70.5% in RPL and in 53.5% in controls; theMallele was significantly associated with an increased risk of RPL (adjusted odds ratio [ORadj]=2.07; 95% confidence interval [CI]; p

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.

Paraoxonase 1 (PON1), residing almost exclusively on HDL, was discovered because of its hydrolytic activity towards organophosphates. Subsequently, it was also found to hydrolyse a wide range of substrates, including lactones and lipid hydroperoxides. PON1 is critical for the capacity of HDL to protect LDL and outer cell membranes against harmful oxidative modification, but this activity depends on its location within the hydrophobic lipid domains of HDL. It does not prevent conjugated diene formation, but directs lipid peroxidation products derived from these to become harmless carboxylic acids rather than aldehydes which might adduct to apolipoprotein B. Serum PON1 is inversely related to the incidence of new atherosclerotic cardiovascular disease (ASCVD) events, particularly in diabetes and established ASCVD. Its serum activity is frequently discordant with that of HDL cholesterol. PON1 activity is diminished in dyslipidaemia, diabetes, and inflammatory disease. Polymorphisms, most notably Q192R, can affect activity towards some substrates, but not towards phenyl acetate. Gene ablation or over-expression of human PON1 in rodent models is associated with increased and decreased atherosclerosis susceptibility respectively. PON1 antioxidant activity is enhanced by apolipoprotein AI and lecithin:cholesterol acyl transferase and diminished by apolipoprotein AII, serum amyloid A, and myeloperoxidase. PON1 loses this activity when separated from its lipid environment. Information about its structure has been obtained from water soluble mutants created by directed evolution. Such recombinant PON1 may, however, lose the capacity to hydrolyse non-polar substrates. Whilst nutrition and pre-existing lipid modifying drugs can influence PON1 activity there is a cogent need for more specific PON1-raising medication to be developed.

Background: 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. Subjects and Methods: A total of 30 patients on hemodialysis were included. Pre- and post-dialysis blood samples were collected to analyze the activity of PON1 in the first 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. Results: We found that post-dialysis PON1 activity was significantly higher than pre-dialysis activity in both the first use and sixth reuse (P < 0.001). Conclusion: The practice of reusing the dialyzer did not interfere with the improvement of PON1 activity after the hemodialysis session. [ABSTRACT FROM AUTHOR]

Copyright of Acibadem Saglik Bilimleri Dergisi is the property of Acibadem University Medical School and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Paraoxonase 1 (PON1) plays a role in regulating reverse cholesterol transport and has antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities. Scientists are currently focused on the modulation of PON1 expression using different pharmacological, nutritional, and lifestyle approaches. We previously isolated a novel active compound from Nannochloropsis microalgae—lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS)—which increased PON1 activity, HDL-cholesterol efflux, and endothelial nitric oxide release. Here, to explore this important lipid moiety's effect on PON1 activities, we examined the effect of synthesized lipid derivatives and endogenous analogs of lyso-DGTS on PON1 lactonase and arylesterase activities and LDL oxidation using structure–activity relationship (SAR) methods. Six lipids significantly elevated recombinant PON1 (rePON1) lactonase activity in a dose-dependent manner, and four lipids significantly increased rePON1 arylesterase activity. Using tryptophan fluorescence-quenching assay and a molecular docking method, lipid–PON1 interactions were characterized. An inverse correlation was obtained between the lactonase activity of PON1 and the docking energy of the lipid–PON1 complex. Furthermore, five of the lipids increased the LDL oxidation lag time and inhibited its propagation. Our findings suggest a beneficial effect of lyso-DGTS or lyso-DGTS derivatives through increased PON1 activity and prevention of LDL oxidation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Background The use of labor induction to shorten the duration of a pregnancy has increased steadily during the last few decades. Paraoxonase 1 levels were observed to be higher in the oxytocin-induced group than in the spontaneous labor group. Objective To compare the influence of induced labor on fetal Apgar score and birthweight, and to measure the level of oxidative stress (paraoxonase 1) experienced during labor by the neonates of pregnant women undergoing induced or spontaneous birth. Methods A case control study that was conducted in the Department of Obstetrics and Gynecology, Azadi Teaching Hospital, Kirkuk during a period of nine months from 10th of February till 10th of November 2019. It included 60 healthy pregnant women with singleton pregnancy and viable fetus attending the labor room of the hospital. They were divided into two groups: Case group included 30 pregnant women who underwent oxytocin-induced labor and control group included 30 pregnant women underwent spontaneous vaginal delivery in latent phase of first stage labor without oxytocin induction. A five ml of blood was drawn from the umbilical artery to measure Paraoxonase 1 level. Pregnancy outcome was also monitored. Results The mean of Paraoxonase 1 enzyme was significantly higher in women who underwent oxytocininduced labor than that in women who underwent vaginal delivery without oxytocin induction. No significant differences between study groups regarding birthweight, Apgar score 1 min, Apgar score 5 min, packed cell volume, and hemoglobin F. Conclusion Serum Paraoxonase 1 as a marker was elevated in neonates of pregnant women who underwent oxytocin induced labor without a significant effect on Apgar score of neonates or its birthweight. [ABSTRACT FROM AUTHOR]

Psoriasis is a systemic disease that is linked to cardiometabolic complications. Paraoxonase 1 (PON1) exerts anti-atherogenic properties. Pentraxin 3 (PTX3) is related to heart failure and atherosclerosis. We aimed to evaluate the protein levels in psoriatic patients and explore possible relations with disease activity, metaflammation parameters and systemic treatment. Thirty-three patients with plaque-type psoriasis and eleven healthy controls were enrolled in the study. Blood samples were collected before and after three months of therapy with acitretin or methotrexate. Serum proteins levels were evaluated using Bio-Plex 200 System. The mean serum pentraxin 3 level was significantly higher in patients with psoriasis, compared to controls (p < 0.01). Significant negative correlations between PTX3 with triglycerides in overweight patients, with glucose, cholesterol and triglycerides in obese patients, and with cholesterol and triglycerides in severe psoriatics were noted (all p < 0.05). After the treatment, PTX3 significantly decreased (p < 0.05). The mean serum PON1 in psoriatic patients did not differ, compared to the controls (p > 0.05). In psoriatics of normal weight, PON1 correlated negatively with liver enzymes activity (p < 0.05). PTX3 might exert a protective role in terms of cardiometabolic disorders development, especially in overweight and obese or most severe psoriatics. PON1 could serve as an indicator of the liver disorders in psoriasis. [ABSTRACT FROM AUTHOR]

Paraoxonase 1 (PON1) is a well recognised member of human endogeneous free radical scavenging systems and its polymorphism and enzyme activity are attributed to various different cancer formations. We aimed to study the Paraoxonase 1 (PON1) polymorphism and enzyme activity in colorectal cancer patients. Peripheral blood samples for DNA extraction were collected from 54 colorectal cancer patients and 85 healthy individuals. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques were used for determination of the PON1192 polymorphism. The frequency of AA genotype was greater than BB and AB genotypes in all groups (n:65 with 46.8%; n:15 with 10.8% and n:59 with 42.4%, respectively). In both tumor groups, PON activities were significantly lower than the control group (p

The lactonase activity of paraoxonase 1 (PON1) has a crucial antiatherogenic function, and also serves as an important biochemical marker in human blood because the aberrant lactonase activity of PON1 is a key indicator for a number of diverse human diseases. However, no sensitive fluorescence assays that detect PON1 lactonase activity are available. We report the synthesis of two fluorescence turn-on chemical probes 16a and 16b (16) able to quantify PON1 lactonase activity. The chemical probes were constructed utilizing a disulfide-containing bicyclononyne, derivatives of rhodamine B and carboxyfluorescein, and reactions including copper-free azide–alkyne cycloaddition. Fluorescence quenching in 16 was characterized by spectroscopic studies and was mainly attributed to the effect of contact quenching. Kinetic analysis of 16b confirmed the outstanding reactivity and specificity of 16b with thiols in the presence of general base catalysts. The 16b-based assay was employed to determine PON1 lactonase activity, with a linear range of 10.8–232.1 U L−1 and detection limit (LOD) of 10.8 U L−1, to quantify serum PON1 activity in human sera, and to determine the Ki of 20.9 μM for the 2-hydroxyquinoline inhibition of PON1 lactonase. We are employing 16b to develop high-throughput assays for PON1 lactonase activity. [ABSTRACT FROM AUTHOR]

Objectives: There are many mechanisms associated with the onset and development of osteoporosis. The purpose of our study is to investigate the relationship between the fasting blood sugar, lipid profile, bone mineral density (BMD) values, and total antioxidant status (TAS), total oxidant status (TOS) levels, and paraoxonase 1 (PON1), arylesterase (ARE) enzyme activities in postmenopausal women. Materials and Methods: Our study included 95 patients diagnosed as being postmenopausal. The patients were divided into three study groups, which were the control (T-score>-1; n=33 with normal BMD, osteopenia (-2.50.05). Accordingly; the comparison of the control group with the osteopenia and osteoporosis groups revealed that serum PON1 enzyme activity was significantly increased in the control group (p<0.05). Conclusion: The results of the study suggest that increased age, duration of menopause, and oxidative stress, as well as decreased PON1 enzyme (an antioxidant enzyme) activity, lead to increased osteoporosis, independently of the lipid profile and serum fasting blood sugar.. [ABSTRACT FROM AUTHOR]