Paraoxonase Enzyme Research Articles

Comparative Study of Human Serum Paraoxonase-1 (PON-1) Activity in Type 2 Diabetes Mellitus: Insights into Oxidative Stress and Antioxidant Defence

Diabetes mellitus is a disease characterized by chronic high blood sugar levels resulting from defects in insulin secretion, insulin action, or both. Prolonged high blood glucose can increase production of reactive oxygen species, leading to elevated oxidative stress. The enzyme paraoxonase-1 (PON1), made in the liver and transported on high-density lipoprotein (HDL), acts as an antioxidant and can counter oxidative stress. This study aimed to compare PON1 activity between healthy controls, obese type 2 diabetics, and non-obese type 2 diabetics. There were 30 healthy controls, 30 obese type 2 diabetics (group I), and 30 non-obese type. Additionally, fasting lipid profiles, fasting plasma glucose, uric acid, albumin, and total bilirubin levels were determined using a clinical chemistry analyzer. The goal was to evaluate differences in PON1 activity as well as metabolic parameters between the three study groups. The results In comparison to the healthy control group, the diabetes group had Significantly higher blood sugar, serum cholesterol, serum triglycerides, serum LDL, and serum uric acid levels, Compared to the healthy control group, PON was Significantly lower in group II patients, Conclusion that Obese type 2 DM patients had significantly lower PON1 and HDL-C levels, which may indicate That the overweight has lessened biochemical functions for these substances. As dyslipidemia, insulin resistance, and high blood pressure are thought to be crucial factors in the cause of metabolic conditions in obese people, the reduced paraoxonase level may increase their likelihood of developing these conditions.

Abstract 4137895: Serum High-density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events after Stent Implantation in Patients with Stable Angina Pectoris

Background: Poor clinical outcomes for patients undergoing hemodialysis (HD) after drug-eluting stent (DES) implantation have been reported. High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease, and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. The aim of this study was to investigate the relationship between plasma MPO and serum PON-1 levels after implantation of DES in patients with stable angina pectoris (SAP) with and without HD. Methods: Serum PON-1 concentrations and PON-arylesterase activity were measured in 183 patients with SAP after DES implantation (HD group, n=37; non-HD group, n=146) with a sandwich ELISA method. Cardiovascular events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction, cerebral infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Serum PON-1 concentrations and PON-arylesterase activity were significantly lower in the HD group than in the non-HD group (PON-1 concentrations, P<0.0001; PON-arylesterase activity, P<0.0001). In addition, plasma MPO in patients undergoing HD were significantly higher than in patients not undergoing HD (P<0.0001). Moreover, plasma MPO showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity (concentration: R= -0.24, P=0.0013; arylesterase-activity: R=-0.24, P=0.0014). Cardiovascular event rates were significantly higher in the HD group than in the non-HD group (67.6% vs. 43.8%, P<0.01). Kaplan-Meier survival analysis showed that the low-PON-1 group (<58.0 mg/mL, median) had a significantly worse outcome than the high-PON-1 group ( P =0.013). Multivariate analysis showed that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.93; 95% confidence interval, 1.10 to 3.40, P =0.024). Conclusions: These findings demonstrate that plasma MPO have a significant inverse correlation with PON-1 in patients undergoing HD and suggest that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression and destabilization of human coronary atherosclerotic lesions in patients with SAP who undergo HD following DES implantation.

Role of Paraoxonase 2 in Airway Epithelial Response to Oxidant Stress.

Asthma is a widespread chronic lung disease characterized by airway inflammation and hyperresponsiveness. This airway inflammation is classified by either the presence (T2-high) or absence (T2-low) of high levels of eosinophils. Because most therapies for asthma target eosinophils and related pathways, treatment options for T2-low disease are limited. New pathophysiologic targets are needed. Oxidant stress is a common feature of T2-low disease. Airway epithelial expression of the antioxidant enzyme Paraoxonase 2 (PON2) is decreased in a well-recognized population of people with T2-low asthma and people with obesity and asthma. As a potential mechanism of increased oxidant stress, we measured the role of PON2 in lung oxidant responses using an environmentally relevant in vivo murine oxidant exposure (i.e., ozone) and in vitro studies with an immortalized human airway epithelial cell line BEAS-2B. Pon2-deficient (Pon2-/-) mice developed increased airway hyper-responsiveness compared to wild-type controls. Despite reduced alveolar macrophage influx, Pon2-/- mice exhibited increased nitrite production. In human airway epithelial cells incubated with hydrogen peroxide, PON2 knockdown (PON2KD) decreased mitochondrial function and inner mitochondrial membrane potential. These findings suggest that PON2 functions in defending against airway epithelial oxidant stress. Further studies are needed to elucidate the mechanisms linking PON2, oxidant stress, and asthma pathogenesis.

Decreased plasma in basal cell cancer

Aim Basal cell carcinoma (BCC) is one of the most common malignant non-melanoma carcinomas and is an important health problem for all countries. There are many studies on the effect of human lipoprotein metabolism and high-density lipoprotein (HDL-C) function on skin cells, but there are no detailed clinical studies on BCC yet. In addition, higher phospholipid and cholesterol content was found in cancerous and precancerous lesions of the skin compared to normal tissue. The aim of our study was to evaluate the lipid profile in patients with BCC and to try to find any relationship between BCC and molecules that have an important place in HDL-C functionality. Methods The patient group consisted of 39 patients who were clinically diagnosed with BCC by biopsy in hospital clinics. The control group (n:44) was randomly selected from patients of the same age group without a diagnosis of BCC who applied to different clinics of the same hospital. Routine lipid level, Apolipoprotein A1 (Apo-A1) level and Paraoxonase (PON- 1) enzyme measurements were made from serum samples taken from the patients and control groups participating in the study. Results The most important findings of this study, a statistically significant decrease in serum Apo-A1 level and a decrease trend in PON-1 enzyme can be considered in BCC patients compared to control groups. Conclusion Lipid metabolism and HDL functionality, may play a role in the development of BCC. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1060-1067

The Effects of PON1 (Q192R, rs662) Gene Polymorphism, Heavy metals and Oxidative Stress on Risk of Recurrent Spontaneous Abortion in Samples of Iraqi Women

Recurrent spontaneous abortion (RSA) is defined as the occurrence of two or more spontaneous pregnancy losses before reaching the midpoint of gestation. Oxidative stress plays a pivotal role in the pathogenesis of RSA, serving as a key factor in its underlying causes. This research aims to investigate the connection between the Q192R polymorphisms identified in the PON1 gene, responsible for encoding an antioxidant enzyme and the vulnerability to RSA. Paraoxonase 1 (PON1) is a critical enzyme in the body's antioxidant defence system, safeguarding cells against damage caused by reactive oxygen species and heavy metal concentrations that affect pregnancy. The most prevalent PON1 polymorphism is Q192R (rs662), known to influence the antioxidant activity and power of the PON1 enzyme. In this research, blood samples were collected from two groups: 50 women with RSA and 50 women who were apparently in good health. Following DNA extraction, high-resolution melting (HRM) analysis was used to identify the studied SNP; Elisa was used to determine DNA damage and MDA concentrations in serum and heavy metals were determined by a Graphite Furnace-Atomic Absorption Spectrophotometer (GFAAS). The results of this study showed significantly higher levels of 8-OHdG, MDA, arsenic and lead in serum in RSA patients than in apparently healthy women. The genotype findings indicated that the prevalence of the QR (AG) genotype in women experiencing recurrent spontaneous abortion was notably greater than that in seemingly healthy women (74% compared to 16%, respectively, with an odds ratio of 27.2). The values of allele frequency for the A allele were 0.76 and 0.51 for apparently healthy women and women with recurrent spontaneous abortion respectively. The G allele frequency was 0.24 and 0.49 for apparently healthy women and women with recurrent spontaneous abortion respectively. The heterozygous QR genotype is related to the risk of RSA and the minor allele (G allele) is increased in women with RSA.

A comprehensive insight from molecular docking and dynamics with clinical investigation on the impact of direct oral anticoagulants on atheroprotective protein in atrial fibrillation

BackgroundDirect oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses.MethodsWe focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration.ResultsOur computational investigation showed rivaroxaban (−4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (−5.97 kcal/mol) and dabigatran (−9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control.ConclusionOverall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.

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

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

Effects of thymoquinone and the curcumin analog EF-24 on the activity of the enzyme paraoxonase-1 in human glioblastoma cells U87MG

The spices and aromatic herbs were used not only in cooking to add flavour and smell to dishes but also for medicinal use. Nigella sativa, also called black cumin, is one of the species that contains an important bioactive component, thymoquinone (TQ), which has antioxidant, anti-inflammatory, antimicrobial, and antidiabetic effects. Curcuma longa, which also includes curcumin, has numerous anti-cancer properties. However, the bioavailability of curcumin is lower than that of its analogs. An analog of curcumin (EF-24), which has better bioavailability than curcumin, is capable of exerting a high anti-cancer effect. In our study, we determined the effects of PON1 enzyme activity on the proliferation and aggressiveness of glioblastoma cancer treated with TQ and EF-24 from lysates of the glioblastoma cell line U87MG. The results were determined as increased PON1 activity after treatment with TQ and EF-24 in the U87MG cell line (p < 0.0001).

Corinthian Currants Promote the Expression of Paraoxonase-1 and Enhance the Antioxidant Status in Serum and Brain of 5xFAD Mouse Model of Alzheimer's Disease.

Paraoxonase-1 (PON1), a serum antioxidant enzyme, has been implicated in Alzheimer's disease (AD) pathogenesis that involves early oxidative damage. Corinthian currants and their components have been shown to display antioxidant and other neuroprotective effects in AD. We evaluated the effect of a Corinthian currant paste-supplemented diet (CurD), provided to 1-month-old 5xFAD mice for 1, 3, and 6 months, on PON1 activity and levels of oxidation markers in serum and the brain of mice as compared to a control diet (ConD) or glucose/fructose-matched diet (GFD). Administration of CurD for 1 month increased PON1 activity and decreased oxidized lipid levels in serum compared to ConD and GFD. Longer-term administration of CurD did not, however, affect serum PON1 activity and oxidized lipid levels. Furthermore, CurD administered for 1 and 3 months, but not for 6 months, increased PON1 activity and decreased free radical levels in the cortex of mice compared to ConD and GFD. To probe the mechanism for the increased PON1 activity in mice, we studied the effect of Corinthian currant polar phenolic extract on PON1 activity secreted by Huh-7 hepatocytes or HEK293 cells transfected with a PON1-expressing plasmid. Incubation of cells with the extract led to a dose-dependent increase of secreted PON1 activity, which was attributed to increased cellular PON1 expression. Collectively, our findings suggest that phenolics in Corinthian currants can increase the hepatic expression and activity of antioxidant enzyme PON1 and that a Corinthian currant-supplemented diet during the early stages of AD in mice reduces brain oxidative stress.

The Role of Polyphenols in Modulating PON1 Activity Regarding Endothelial Dysfunction and Atherosclerosis.

The incidence and prevalence of cardiovascular diseases are still rising. The principal mechanism that drives them is atherosclerosis, an affection given by dyslipidemia and a pro-inflammatory state. Paraoxonase enzymes have a protective role due to their ability to contribute to antioxidant and anti-inflammatory pathways, especially paraoxonase 1 (PON1). PON1 binds with HDL (high-density lipoprotein), and high serum levels lead to a protective state against dyslipidemia, cardiovascular diseases, diabetes, stroke, nonalcoholic fatty liver disease, and many others. Modulating PON1 expression might be a treatment objective with significant results in limiting the prevalence of atherosclerosis. Lifestyle including diet and exercise can raise its levels, and some beneficial plants have been found to influence PON1 levels; therefore, more studies on herbal components are needed. Our purpose is to highlight the principal roles of Praoxonase 1, its implications in dyslipidemia, cardiovascular diseases, stroke, and other diseases, and to emphasize plants that can modulate PON1 expression, targeting the potential of some flavonoids that could be introduced as supplements in our diet and to validate the hypothesis that flavonoids have any effects regarding PON1 function.

Increased oxidative stress in shoe industry workers with low-level exposure to a mixture of volatile organic compounds.

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2 •-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.

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

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

Association of the polymorphism of the Pon-1 locus with the concentration of Paraoxonase-1 and post-thaw sperm viability in pig

The objective of the present work was to correlate the expression of the PON-1 locus polymorphism, the concentration of the enzyme paraoxonase 1 in seminal plasma and the effect on post-thawing sperm viability in the pig. Nine ejaculates from 3 boars were used, to obtain seminal plasma; part of the ejaculates was centrifuged at 800 g/10 min; the material obtained was stored at -20°C until use. To freeze the semen, the samples were diluted 1:1 in commercial diluent (Magapor®) at 37°C and the temperature was gradually lowered to 16°C. They were transported to the laboratory protected from light, and kept at the same temperature in the laboratory for 24 h. After this, they were frozen using the glycerolation technique and a portion was cryopreserved by adding 20% of seminal plasma to the conservation medium and another portion was made without seminal plasma. The concentration of PON-1 was determined by an enzyme-linked immunosorbent assay (ELISA). The functional status of the plasma membrane was evaluated by chlortetracycline staining. The amplification of a fragment of the PON-1 gene was carried out by PCR and the identification of allelic variability by the analysis of Restriction Fragment Length Polymorphism (RFLP), with the enzymes HinfI and FokI, from a DNA sample of each individual. The results were analyzed by analysis of variance (ANOVA) and Spearman correlation, with the use of statistical software (Statistica V10 for Windows). In electrophoresis of enzymatic digestion with the enzyme HinfI All the expected fragments were obtained, with the FokI enzyme a mutation was observed in one individual. No correlation was observed (R=-0.1, P&gt;0.05) between the concentration of the paraoxonase-1 enzyme in seminal plasma and the observed mutations. As well as the concentration of the enzyme paraoxonase-1 in the ejaculates was 1.8 to 2.7 ng/mL and this had no statistically significant difference in the seminal plasma of the ejaculates analyzed (P&gt;0.05). As well as with sperm viability in thawed semen (P&gt;0.05).

Study the effectiveness of paraoxonase-1 and creatine kinase enzymes in acute myocardial infarction patients

Study the effectiveness of paraoxonase-1 and creatine kinase enzymes in acute myocardial infarction patients

Signature of paraoxonases in the altered redox homeostasis in Alzheimer's disease

Paraoxonase (PON) enzymes (PON1, PON2 and PON3) exert antioxidant properties through arylesterase, lactonase and paraoxonase activities. Increasing findings suggested their potential involvement, particularly PON1 and PON2, in Alzheimer's disease (AD), a neurodegenerative pathology characterized by early oxidative stress. Specifically, decreased serum PON1-arylesterase and lactonase activities seem to be associated with an increased brain oxidative damage in early AD, leading to hypothesize that PON activity alterations might be an early event in AD. To address this hypothesis, the levels of 4-hydroxynonenal (4-HNE; i.e. a marker of oxidative stress damage) along with the protein expression and enzymatic activity of PON1 and PON2 have been investigated in the brain and serum of young [Postnatal day (PD)8–10, 20–25 and 60–65] asymptomatic 3xTg-AD female mice, one of the most used transgenic models of AD.At PD 8–10, there were no differences in hippocampus and prefrontal cortex (PFC) 4-HNE expression levels between 3xTg-AD mice compared to controls (Non-Tg mice). On the other hand, significant increased levels of 4-HNE were detected in PD 20–30 3xTg-AD mice hippocampus, while a significant reduction was observed in 3xTg-AD group at PD 60–65. In the PFC, 4-HNE levels were significantly reduced in 3xTg-AD mice brain at PD 20–30, while no differences in 4-HNE levels were detected at PD 60–65.No significant differences in arylesterase and lactonase activities were observed in the plasma of 3xTg-AD and Non-Tg mice at the different considered ages. Compared to Non-Tg mice, a reduction of brain arylesterase activity was found in 3xTg-AD female at PD 20–30 and PD 60–65, but it was significant only in the younger group. Finally, a similar trend was observed also for PON1 and PON2 protein levels, with both significantly, and solely, decreased in 3xTg-AD mice brain at PD 20–30.Overall, these findings suggest that the altered oxidative stress homeostasis in the 3xTg-AD female mice may be related to an early reduction in activity and expression of PONs enzymes most likely via a reduced brain arylesterases activity.

PON1 has palmitoyl-protein thioesterase (PPT) activity, and can affect the presence of SR-B1 on the endothelial cell membrane.

The high-density lipoprotein (HDL)-associated enzyme paraoxonase 1 (PON1) is expressed almost exclusively in the liver and is then transported by HDL to the peripheral tissues. The lipophilic nature of PON1 enables its easy exchange between the lipoprotein and cell membranes in a process that is dependent on the HDL receptor scavenger receptor class B, type 1 (SR-B1). In endothelial cells, PON1 binding to the cell membrane leads to its internalization by endocytosis and subsequent lysosomal degradation. PON1 is a "promiscuous" enzyme with unusually broad substrate specificity in vitro, but its actual function and substrate are still unknown. The enzyme requires a lipid environment and becomes completely inactive upon delipidation. However, when PON1 binds HDL, its active site faces the lipoprotein's core and is inaccessible to external substrates. Hence, the HDL-bound PON1 is inactive toward substrates outside the particle's lipid core and is rapidly degraded and becomes inactive upon internalization. Consequently, the enzyme is only active in the cell membrane during its transit from HDL to the cytoplasm. To assign a function to PON1, we investigated whether it is a palmitoyl-protein thioesterase (PPT) that can hydrolyze the palmitoyl moieties of membrane proteins involved in HDL and cholesterol transport, such as SR-B1, ABCA1, or their neighboring caveola proteins to facilitate the release of HDL or trigger its endocytosis. This study shows that PON1 can hydrolyze palmitoyl-cysteine thioester bonds in vitro, has direct or indirect PPT activity in vivo, and can significantly decrease the presence of SR-B1 in the endothelial membrane.

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

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

Effects of Seven Weeks of Combined Physical Training on High-Density Lipoprotein Functionality in Overweight/Obese Subjects.

Our study aimed to investigate the effects of exercise on HDL composition and functional properties in overweight/obese subjects. Eighteen overweight/obese subjects (nine F and nine M, BMI = 30.3 ± 3 kg/m2) attended supervised training for 7 weeks. The protocol included combined resistance and conditioning training four to five times each week. The activity of the antioxidant enzyme paraoxonase-1 (PON1) associated with HDL was evaluated in all subjects before and after the training intervention. Moreover, myeloperoxidase (MPO) levels and oxidative stress markers (ox-LDLs and total antioxidant capacity) were studied in the serums of the subjects. At the end of the intervention, the activity of PON1 was increased (p < 0.0001), and MPO levels and the MPO/PON1 ratio were decreased (p < 0.0001). In addition, a significant improvement in muscle strength and maximal oxygen uptake (VO2max) (p < 0.0001) and a significant reduction in total and visceral adipose tissue mass (p < 0.001) and waist circumference (p < 0.008), without any significant decrease in body weight, were observed. A significant correlation was established between serum MPO/PON ratios, HDL redox activity and ox-LDLs. In conclusion, our results demonstrate that exercise training, without modifications of dietary habits, improved HDL functionality in overweight/obese adults, without any significant reduction in BMI or modifications of glucose and lipid biochemical parameters.

Evaluation of oxidative stress biomarkers together with myeloperoxidase/paraoxonase-1 and myeloperoxidase/high density lipoprotein cholesterol in ST-elevation myocardial infarction

Abstract Objectives Oxidative stress is closely associated with atherosclerosis and acute coronary syndromes. The purpose of this study was to evaluate well-known and proportional oxidative stress biomarkers in ST-Elevation Myocardial Infarction (STEMI) patients. Methods In this single center, prospective and cross-sectional study, 107 individuals (63 patients) were studied. Total oxidative status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), ischemia modified albumin (IMA), myeloperoxidase (MPO), paraoxonase-1 (PON-1) and arylesterase (AREase) enzyme activities as well as MPO/PON-1, MPO/AREase and MPO/HDL-C ratios were studied. As short-term in-hospital prognosis biomarkers; in-hospital mortality, early systolic dysfunction and spontaneous complete revascularization were investigated. Results Our results indicated that TOS, OSI, IMA, MPO, MPO/PON-1 and MPO/HDL ratios were significantly higher, PON-1 and AREase were significantly lower in STEMI patients compared to the control group. However, in the regression analysis performed by adjusting the differences between the groups, only IMA was found as an independent risk factor (OR=2.711, 95 % CI=1.094–6.719, p=0.031). In terms of in-hospital short-term prognostic biomarkers, a significant relationship was found only between OSI and spontaneous complete revascularization. The OSI value was higher in the group with TIMI grade 3 flow than in the group with TIMI grade 0–2 flow (2.42 [0.81–4.49] vs. 1.63 [0.33–6.07], p=0.016). Conclusions In STEMI patients, both the well-known (TOS, OSI, and MPO) and proportional (MPO/PON-1 and MPO/HDL cholesterol ratios) oxidative stress markers were elevated and can be considered as having a role in the pathogenesis of STEMI.

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

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