Paraoxonase Enzyme Research Articles

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

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

Formulation of Phytosomes with Extracts of Ginger Rhizomes and Rosehips with Improved Bioavailability, Antioxidant and Anti-Inflammatory Effects In Vivo.

The poor water solubility of natural antioxidants restricts their bioavailability and therapeutic use. We aimed to develop a new phytosome formulation with active compounds from extracts of ginger (GINex) and rosehips (ROSAex) designed to increase their bioavailability, antioxidant and anti-inflammatory properties. The phytosomes (PHYTOGINROSA-PGR) were prepared from freeze-dried GINex, ROSAex and phosphatidylcholine (PC) in different mass ratios using the thin-layer hydration method. PGR was characterized for structure, size, zeta potential, and encapsulation efficiency. Results showed that PGR comprises several different populations of particles, their size increasing with ROSAex concentration, having a zeta potential of ~-21mV. The encapsulation efficiency of 6-gingerol and β-carotene was >80%. 31P NMR spectra showed that the shielding effect of the phosphorus atom in PC is proportional to the amount of ROSAex in PGR. PGR with a mass ratio GINex:ROSAex:PC-0.5:0.5:1 had the most effective antioxidant and anti-inflammatory effects in cultured human enterocytes. PGR-0.5:0.5:1 bioavailability and biodistribution were assessed in C57Bl/6J mice, and their antioxidant and anti-inflammatory effects were evaluated after administration by gavage to C57Bl/6J mice prior to LPS-induced systemic inflammation. Compared to extracts, PGR induced a 2.6-fold increase in 6-gingerol levels in plasma and over 40% in the liver and kidneys, in parallel with a 65% decrease in the stomach. PGR treatment of mice with systemic inflammation increased the sera antioxidant enzymes paraoxonase-1 and superoxide dismutase-2 and decreased the proinflammatory TNFα and IL-1β levels in the liver and small intestine. No toxicity was induced by PGR either in vitro or in vivo. In conclusion, the phytosome formulation of GINex and ROSAex we developed resulted in stable complexes for oral administration with increased bioavailability, antioxidant and anti-inflammatory potential of their active compounds.

Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson's Disease.

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.

Inhibition Effects of Oncological Drugs for Treatment of Cancer, on Paraoxonase-1 Enzyme (PON1) Activity and Cardiovascular Toxicity

Inhibition Effects of Oncological Drugs for Treatment of Cancer, on Paraoxonase-1 Enzyme (PON1) Activity and Cardiovascular Toxicity

Capsazepine (CPZ) Inhibits TRPC6 Conductance and Is Protective in Adriamycin-Induced Nephropathy and Diabetic Glomerulopathy.

Reactive oxygen species (ROS), which excessively arise in diabetes and systemic inflammatory diseases, modify cellular lipids and cellular lipid composition leading to altered biophysical properties of cellular membranes. The impact of lipid peroxidation on transmembrane signaling routes is not yet well studied. The canonical transient receptor potential channel 6 (TRPC6) is implicated in the pathogenesis of several forms of glomerular diseases. TRPC6 is sensitive to membrane stretch and relies on a distinct lipid environment. This study investigates the effect of oxidative alterations to plasma membrane lipids on TRPC6 activity and the function of the glomerular filter. Knockout of the anti-oxidative, lipid modifying enzyme paraoxonase 2 (PON2) leads to altered biophysical properties of glomerular epithelial cells, which are called podocytes. Cortical stiffness, quantified by atomic force microscopy, was largely increased in PON2-deficient cultured podocytes. PON2 deficiency markedly enhanced TRPC6 channel currents and channel recovery. Treatment with the amphiphilic substance capsazepine in micromolar doses reduced cortical stiffness and abrogated TRPC6 conductance. In in vivo studies, capsazepine reduced the glomerular phenotype in the model of adriamycin-induced nephropathy in PON2 knockout mice and wildtype littermates. In diabetic AKITA mice, the progression of albuminuria and diabetic kidney disease was delayed. In summary, we provide evidence that the modification of membrane characteristics affects TRPC6 signaling. These results could spur future research to investigate modification of the direct lipid environment of TRPC6 as a future therapeutic strategy in glomerular disease.

High density lipoprotein heterogeneity & function among Indians with coronary artery disease.

Impaired high density lipoprotein (HDL) functionality has been shown to be associated with cardiovascular disease risk. The study was aimed to identify the alterations in HDL function [antioxidative activity (AOA)] and subfraction distribution between acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) individuals and analysing the accuracy of HDL parameters to discriminate between the groups. HDL subfraction distribution analysis was performed in 200 coronary artery disease patients (ACS and SCAD) and 60 control individuals using dextran sulphate, heparin and manganese chloride precipitation method. In terms of HDL function, AOA was evaluated by dihydrorhodamine-based fluorescent cell-free assay and paraoxonase (PON1) enzyme paraoxonase and arylesterase activity. We found that higher AOA [odds ratio (95% confidence interval {CI})]: 0.09 (0.02-0.44), P<0.01 for SCAD; 0.008 (0.001-0.07), P<0.001 for ACS and higher PON1 activity [0.22 (0.8-0.59), P<0.01 for SCAD; 0.16 (0.06-0.4), P<0.001 for ACS] were associated with a lower odds of developing coronary artery disease (CAD). AOA of apoB-depleted serum was significantly correlated with HDL2-C/HDL3-C (HDL-cholesterol) ratio in controls (r=-0.31, P=0.01) and ACS (r=-0.18, P=0.04). It was observed that AOA and HDL subfraction distribution together could discriminate between the two groups of CAD with an accuracy of 72.8 per cent (P=0.004). Impaired AOA and altered subfraction distribution of HDL may be responsible for its diminished anti-athero protective activity and can discriminate between the two groups of CAD individuals.

Gestational Hypertension and High-Density Lipoprotein Function: An Explorative Study in Overweight/Obese Women of the DALI Cohort.

Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspring. We studied functional parameters of maternal and neonatal HDL in 192 obese women (pre-pregnancy BMI ≥ 29), who were at high risk for GHTN. Maternal blood samples were collected longitudinally at &lt;20 weeks, at 24-28 and 35-37 weeks of gestation. Venous cord blood was collected immediately after birth. Maternal and cord blood were used to determine functional parameters of HDL, such as HDL cholesterol efflux capacity, activity of the vaso-protective HDL-associated enzyme paraoxonase-1, and levels of the HDL-associated anti-inflammatory apolipoprotein (apo)M. In addition, we determined serum anti-oxidative capacity. Thirteen percent of the women were diagnosed with GHTN. While we found no changes in measures of HDL function in mothers with GHTN, we observed impaired HDL cholesterol efflux capacity and paraoxonase-1 activity in cord blood, while serum antioxidant capacity was increased. Of particular interest, increased maternal paraoxonase-1 activity and apoM levels in early pregnancy were associated with the risk of developing GHTN. GHTN significantly impairs HDL cholesterol efflux capacity as well as HDL PON1 activity in cord blood and could affect vascular health in offspring. Maternal paraoxonase-1 activity and apoM levels in early pregnancy associate with the risk of developing GHTN.

Combined Effects of Lycopene and Metformin on Decreasing Oxidative Stress by Triggering Endogenous Antioxidant Defenses in Diet-Induced Obese Mice

Since lycopene has antioxidant activity, its combination with metformin may be useful to contrast diabetic complications related to oxidative stress. This study aimed to investigate the effects of metformin combined with lycopene on high-fat diet (HFD)-induced obese mice. Seventy-two C57BL-6J mice were divided into six groups: C (control diet-fed mice), H (HFD-fed mice for 17 weeks), H-V (HFD-fed mice treated with vehicle), H-M (HFD-fed mice treated with 50 mg/kg metformin), H-L (HFD-fed mice treated with 45 mg/kg lycopene), and H-ML (HFD-fed mice treated with 50 mg/kg metformin + 45 mg/kg lycopene). Treatments were administered for 8 weeks. Glucose tolerance, insulin sensitivity, fluorescent AGEs (advanced glycation end products), TBARS (thiobarbituric acid-reactive substances), and activities of antioxidant enzymes paraoxonase-1 (PON-1; plasma), superoxide dismutase, catalase and glutathione peroxidase (liver and kidneys) were determined. Metformin plus lycopene reduced body weight; improved insulin sensitivity and glucose tolerance; and decreased AGEs and TBARS in plasma, liver and kidneys. Combined therapy significantly increased the activities of antioxidant enzymes, mainly PON-1. Lycopene combined with metformin improved insulin resistance and glucose tolerance, and caused further increases in endogenous antioxidant defenses, arising as a promising therapeutic strategy for combating diabetic complications resulting from glycoxidative stress.

Gradient Boosting Machine Identified Predictive Variables for Breast Cancer Patients Pre- and Post-Radiotherapy: Preliminary Results of an 8-Year Follow-Up Study.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Role of Paraoxonase-1 Enzyme in Prediction of Severity and Outcome of Acute Organophosphorus Poisoning: A Prospective Study

Role of Paraoxonase-1 Enzyme in Prediction of Severity and Outcome of Acute Organophosphorus Poisoning: A Prospective Study

Does oxidative stress promote the effect of the paraoxonase enzyme family (PON) on cancer? A review study to clarify this relationship by PONs

Cancer development and progression are associated with oxidative stress. Oxidative stress can favor high concentrations of reactive oxygen species (ROS), and free radicals are associated with antioxidant metabolism. The human enzyme paraoxonase (PON) contributes to antioxidant metabolism and decreased antioxidant levels. This leads to a high-risk factor for coronary heart disease. This review focuses on specific changes that affect the DNA molecule, and signaling pathways, and regulate the various cancers through the attraction of PON, an enzyme for degrading lipid peroxides within the cell as well as lipoproteins in the bloodstream.

Study of the diagnostic utility of paraoxonase enzyme in serum and bronchoalveolar lavage in patients with lung cancer

Backgrounds PON1 plays a main role in preventing oxidative stress, and also it is important in removal of carcinogenic lipid-soluble radicals caused by lipid peroxidation. Bronchoalveolar lavage (BAL) is a sampling technique used in flexible bronchoscopy that can detect several biochemical agents that could be used as possible lung cancer biomarkers. Objectives To investigate the diagnostic utility of serum and BAL levels of paraoxonase enzyme in patients with lung cancer. Patients and methods The study included two groups: group I consisted of 25 patients diagnosed as having lung cancer, and group II consisted of 15 healthy volunteers. Clinical history taking, physical examination, radiological investigations such as chest radiograph and computed tomography, and routine laboratory tests were done for all studied cases. Serum and BAL samples were collected from all studied cases to evaluate PON1 enzyme activity by ELISA test. Results Paraoxonase enzyme was significantly lower in serum and BAL fluid samples in lung cancer cases compared with healthy persons. A significant positive correlation between PON1 levels was found in BAL and serum, and also there were significant positive correlations comparing PON1 enzymatic activity and lipid parameters (high-density lipoprotein, low-density lipoprotein, and cholesterol). Conclusion Levels of PON1 and its related variables could be used as good biomarkers for assessing patients with lung cancer.

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

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

Suppressed paraoxonase-1 activity associates with elevated oxylipins and the presence of small airways disease in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA)-associated lung disease (LD) associates with significantly increased morbidity and mortality. Although oxidative stress plays an important role in the inflammatory responses in other forms of lung disease, minimal work has evaluated its role in RA-LD. The current work examines the relationship between the anti-oxidant HDL-associated enzyme paraoxonase-1 (PON1), the PON1 Q192R polymorphism, and a targeted oxylipin panel with RA-LD.MethodsThis study was conducted as a retrospective chart review of a longitudinal single-center cohort of 250 RA patients. CT scans of the chest were reviewed by the interpreting radiologist and classified as small airways disease (SAD), interstitial lung disease (ILD), and bronchiectasis. PON1 activity was measured by its lactonase, arylesterase, and paraoxonase functions. The PON1 Q192R polymorphism and a targeted lipidomics panel were performed as previously reported.Results43.2% of the 250 RA patient cohort (n = 108) had available CT scans, including 48 patients (44.4%) with SAD, 27 patients (25.0%) with bronchiectasis, and 16 patients (14.8%) with ILD. Patients with SAD had significantly lower baseline PON1 activity by its arylesterase, and lactonase functions, as well as higher 15-HETE, LTB4, and PGE2 levels compared to those without SAD. These predictors of SAD remained significant after multivariate analysis including known risk factors for RA-LD. Suppressed PON1 activity also correlated with higher levels of 15-HETE and 12-HETE.ConclusionIn a single-center RA cohort, suppressed baseline PON1 activity and elevation in the oxylipins 15-HETE, LTB4, and PGE2 predicted the presence of RA-SAD in longitudinal follow-up.Key Points• Small airways disease (SAD) was present in 44.4% of this rheumatoid arthritis (RA) cohort.• Patients with SAD had significantly lower baseline PON1 activity, as well as higher levels of the oxylipins 15-HETE, LTB4, and PGE2 levels compared to those without SAD.• Further work is warranted to confirm these findings and further define the role of PON1 and lipid oxidation in RA lung disease.

Oxidative stress and PON1 (T172A/L55M) polymorphism: potential risk factors for Osteoarthritis

Objective: To investigate the role of oxidative stress in the progression of osteoarthritis with the genetic determinant of paraoxonase-1 enzyme L55M in osteoarthritis patients. Method: The case control study was carried out at the University of Karachi from April to November 2020, and comprised blood samples of female osteoarthritis patients aged &gt;50 years and healthy controls matched for age and gender. Oxidative stress was assessed by measuring lipid peroxidation product and protein carbonyl content. Activities of paraoxonase-1 paraoxonase and arylesterase were evaluated in the subjects. Protein expression of paraoxonase-1 was also analysed using western blot method. Paraoxonase-1 L55M (rs854560) polymorphism was determined using tetra-amplification-refractory mutation system polymerase chain reaction. Data was analysed using SPSS® Statistics 20.0. Results: Of the 103 subjects, 50(48.5%) were patients and 53(51.5%) were controls. The overall age range was 50-70 years. The extent of malondialdehyde (p&lt;0.001) and protein carbonyl content (p&lt;0.05) were increased significantly in the patients compared to the controls. Activity of paraoxonase and arylesterase was found decreased (p&lt;0.001) in patients compared to the controls. The prevalence of genotype MM was higher in the patients than the controls(p=0.001). L55M was more pronounced in patients suffering than the controls (p=0.01). Conclusion: The elevated levels of malondialdehyde and cabonylated protein content might be associated with osteoarthritis progression. Decreased serum paraoxonase-1 activity with L55M was the major consequence of oxidative stress in female osteoarthritis patients. Key Words: Osteoarthritis, Oxidative stress, Paraoxonase, Polymorphism.

The mechanistic basis for the toxicity difference between juvenile rats and mice following exposure to the agricultural insecticide chlorpyrifos

At high exposure levels, organophosphorus insecticides (OPs) exert their toxicity in mammals through the inhibition of brain acetylcholinesterase (AChE) leading to the accumulation of acetylcholine in cholinergic synapses and hyperactivity of the nervous system. Currently, there is a concern that low-level exposure to OPs induces negative impacts in developing children and the chemical most linked to these issues is chlorpyrifos (CPF). Our laboratory has observed that a difference in the susceptibility to repeated exposure to CPF exists between juvenile mice and rats with respect to the inhibition of brain AChE. The basis for this difference is unknown but differences in the levels of the detoxification mechanisms could play a role. To investigate this, 10-day old rat and mice pups were exposed daily for 7 days to either corn oil or a range of dosages of CPF via oral gavage. Four hours following the last administration of CPF on day 16, brain, blood, and liver were collected. The inhibition of brain AChE activity was higher in juvenile rats as compared to juvenile mice. The levels of activity of the detoxification enzymes and the impact of CPF exposure on their activity were determined in the two species at this age. In blood and liver, the enzyme paraoxonase-1 (PON1) hydrolyzes the active metabolite of CPF (CPF-oxon), and the enzymes carboxylesterase (CES) and cholinesterase (ChE) act as alternative binding sites for CPF-oxon removing it from circulation and providing protection. Both species had similar levels of PON1 activity in the liver and serum. Mice had higher ChE activity in liver and serum than rats but, following CPF exposure, the percentage inhibition was similar between species at an equivalent dosage. Even though rats had slightly higher liver CES activity than mice, the level of inhibition following exposure was higher in rats. In serum, juvenile mice had an 8-fold higher CES activity than rats, and exposure to a CPF dosage that almost eliminated CES activity in rats only resulted in 22% inhibition in mice suggesting that the high serum CES activity in mice as compared to rats is a key component in this species difference. In addition, there was a species difference in the sensitivity of CES to inhibition by CPF-oxon with rats having a lower IC50 in both liver and serum as compared to mice. This greater enzyme sensitivity suggests that saturation of CES would occur more rapidly in juvenile rats than in mice, resulting in more CPF reaching the brain to inhibit AChE in rats.

Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development.

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

Diyabetik Sıçanlarda Vaccinium myrtillus'un Paraoksonaz Aktivitesi, Bazı Biyokimyasal Parametreler ve Pankreas Fonksiyonları Üzerindeki Koruyucu Etkisi

Objective: Diabetes is one of the biggest problems in the field of public health in the world. Vaccinium myrtillus L. extract, among the medicinal plants, has powerful antioxidant activity. For this aim, the possible effects of Vacillus myrtillus extract on serum paraoxonase (PON1), pancreatic enzyme levels, and lipid levels in experimental diabetic rats were investigated.&#x0D; Material and Method: A total of 32 male rats (Wistar albino) were used in this study and divided into four groups. Control (C), diabetic (D), Vaccinium myrtillus (VM), diabetes plus Vaccinium myrtillus (DVM) groups. In D and DVM groups, experimental diabetes was induced using a single dose of intraperitoneal 45 mg/kg streptozotocin. Vaccinium myrtillus extract was administered as 1.2 mg/kg/21 days by oral gavage in VM and DVM groups. At the end of the study; serum HbA1c, lipid parameters, amylase, lipase, and paraoxonase (PON1) enzymes were analyzed.&#x0D; Results: HbA1c was significantly reduced in diabetic groups treated with VM (VM and DVM). Cholesterol, LDL-C, and VLDL-C levels were significantly reduced after VM was administered to diabetic subjects, while other lipids were found to decrease insignificantly. Vaccinium myrtillus extract caused a slight decrease in pancreatic enzymes and a statistically significant increase in paraoxonase enzyme in the DVM group compared to group D.&#x0D; Conclusion: The obtained data support that Vaccinium myrtillus extract may play a potential protective role in preventing diabetes-associated complications.

Phytochemicals as Modulators of Paraoxonase-1 in Health and Diseases

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

Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia.

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-β1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-β1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-β1 concentrations at 24 h.