Paraoxonase Activity Research Articles

The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1

The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease.

Link Between Metabolic Syndrome, Blood Lipid Markers, Dietary Lipids, and Survival in Women with Early-Stage Breast Cancer

Background/Objectives: Nearly 10% of cancers could be prevented through dietary changes. In addition, breast cancer (BC) is the most common cancer in women worldwide. Inadequate diet may lead to several metabolic abnormalities, including metabolic syndrome (MS). The goal of our study is to evaluate the link between survival after BC and MS, as well as diet lipids and circulating lipids. Methods: This study was performed in an early-stage BC cohort (n = 73): MS, dietary lipids, and circulating biological parameters, including leucocyte expression in cholesterol carriers (ATP-binding cassette transporter ABCA1, ABCG1), were determined before any medication intervention. The data of each patient were analyzed using univariate logistic regression and are expressed by HR, 95%CI [5th–95th]. All these parameters were explored with survival parameters using Cox regression analyses. Results: Overall survival (OS) and invasive disease-free survival (iDFS) were significantly longer for the women without metabolic syndrome with HR 4.7 [1.11–19.92] and p = 0.036, and 3.58 [1.23–10.44] and p = 0.019, respectively. The expression of ABCG1 in peripheral leucocytes, an ATP-binding cassette transporter involved in cholesterol and phospholipid trafficking, is significantly associated with iDFS (1.38 [1.1–1.9], p = 0.0048). MS is associated with more pejorative survival parameters in early-stage breast cancer. Paraoxonase (or PON) activities differ according to PON gene polymorphism, but also diet. A link between PON activities and survival parameters was suggested and needs to be clarified. Conclusions: This study emphasizes the link between survival parameters of early-stage breast cancer, metabolic syndrome, and some parameters related to lipid metabolism.

New strategies to classify canine pleural effusions and the diagnostic value of acute phase proteins, amylase, and adenosine deaminase in pleural exudates.

In dogs, simplified Light's criteria can discriminate transudates from exudates. Other tests used in human medicine are pleural effusion cholesterol (CHOLPE) and butyrylcholinesterase [BChEPE], the pleural effusion/serum ratio of these analytes (CHOLratio and BChEratio), and the serum albumin minus pleural effusion albumin gradient (SEAG). We aimed to assess the diagnostic accuracies of different biomarkers in dogs with pleural effusion in differentiating exudates from transudates. Secondarily, we evaluated the potential diagnostic utility of pleural effusion acute phase proteins, amylase, and adenosine deaminase in discriminating causes of exudative effusions. Cross-sectional study including 68 client-owned dogs with pleural effusion. There were 48 exudates (10 septic, 16 neoplastic, 9 hemorrhagic, and 13 classified as other exudates) and 20 transudates. All the variables analyzed, except SEAG, were significantly different between exudates and transudates. Using the cut-off values adopted in human literature, accuracies for CHOLPE, CHOLratio, BChEPE, and BChEratio were between 82.35% and 85.29%; all values were significantly lower compared with the previously published simplified Light's criteria accuracy (i.e., 98%, p < .001 for all comparisons). We found the accuracy of the simplified Light's criteria to be similar to what has been previously reported (95.59%, p = .238). Paraoxonase-1 (PON-1PE) activity and the pleural effusion/serum paraoxonase-1 ratio (PON-1ratio) were significantly lower in exudative neoplastic effusions than in exudative hemorrhagic (p = .004 and p = .001) and septic (p = .004 and p < .001) effusions. Simplified Light's criteria were the best method for discriminating transudates from exudates, and a low PON-1PE activity and PON-1ratio in exudative effusions may suggest an underlying neoplasia.

Assessment of Paraoxonase 1 and Arylesterase Activities and Lipid Profile in Bodybuilders: A Comparative Study of Physical Activity and Anthropometry on Atherosclerosis.

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.

The Apoptotic, Cytotoxic, and Anti-migration Effects of Sodium Deoxycholate in a Breast Cancer Cell Line and its Modulation on PON1 as a Predictive Risk Marker.

Breast cancer is the most prevalent cancer among women and is usually treated with antineoplastic drugs. The present study examines the influence of sodium deoxycholate on the molecular pathways underlying apoptosis, cytotoxicity, and the modulation of PON1 in the MCF-7 breast cancer cell line. Various doses were administered to test the hypothesis that it could potentially affect cancer cells. The study examined the cytotoxic effect of sodium deoxycholate on MCF-7 cells and human mammary epithelial cells (CRL-4010) using the MTT method to detect its anticancer properties. Subsequently, the efficacy of the active dose on DNA fragmentation and apoptosis was examined using the apoptotic DNA ladder and Western blot methods. Additionally, oxidative stress index and cell migration tests were conducted. Notably, sodium deoxycholate did not cause DNA damage despite demonstrating cytotoxic effects on cells. The study found that sodium deoxycholate increased the levels of several pro-apoptotic proteins, leading to apoptosis. Moreover, it markedly diminishes the activity of paraoxonase and arylesterase of PON1, which are predictive risk markers for cancer. Furthermore, it was found to delay cell migration in a time-dependent manner. These findings suggest that sodium deoxycholate exhibits an antimetastatic effect in breast cancer cells, could be a valuable subject for further cancer research.

Exploring the Relationship between Canine Paraoxonase-1 (PON-1) Serum Activity and Liver Disease Classified by Clinico-Pathological Evaluation.

Paraoxonase-1 (PON-1), a liver-synthesized enzyme, acts as a negative acute-phase reactant during systemic inflammation in dogs. Given the hepatic synthesis of this enzyme, the presence of liver diseases may influence PON-1, thus affecting its reliability as a biomarker for inflammatory/oxidative systemic diseases. The aim of this study is to investigate PON-1 activity variations among dogs suspected of liver injury or failure, evaluating the influence of hepatic diseases on PON-1 activity. A total of one-hundred-sixty dogs were retrospectively enrolled and categorized into three groups based on clinical presentation and laboratory results: control (C = 20), suspected liver injury (INJ = 114), and suspected liver failure (FAIL = 26). The INJ group was further divided into subgroups based on the severity of the alanine aminotransferase (ALT) increase. Both the INJ and FAIL groups were further divided based on serum macroscopic appearance. The PON-1 activity was quantified using a paraoxon-based method, which is already validated in dogs. No significant difference in PON-1 activity was observed between the C and INJ groups, despite a significant increase in the subgroups with moderate and severe elevations of ALT. The dogs with icteric serum exhibited decreased PON-1 activity, while lipemic serum was associated with an increased PON-1 activity. A significant reduction in PON-1 activity was noted in the FAIL group, compared to both C and INJ groups (p < 0.0001), regardless of serum appearance. Given the retrospective nature of this study, additional evaluations (e.g., histopathology, imaging) were not performed. The results obtained here suggest the importance of interpreting PON-1 activity cautiously in dogs with suspected liver disease.

Investigation of the Effect of Omega-3 Fatty Acids on Antioxidant System and Serum Aluminum, Zinc, and Iron Levels in Acute Aluminum Toxicity.

Aluminum (Al), one of the three most prevalent metals in the Earth's crust, adversely impacts all metabolic systems of living organisms due to its extensive utilization by humans. It is known that omega-3 fatty acids (ω-3FA) protect the organism against diseases and have positive effects on the immune system. The aim of the study was to investigate the effect of ω-3FA on 8-OH-2-deoxyguanosine (8-OHdG), glutathione (GSH) levels and adenosine deaminase (ADA), paraoxonase (PON), and catalase (CAT) activities in rats with acute aluminum toxicity. The study also aimed to investigate the antioxidant system, as well as Al, zinc (Zn), and iron (Fe) levels. Forty Sprague-Dawley rats (n = 40) were used in the study and the rats were divided into four equal groups (n = 10). In group I, 0.5mL of 0.9% saline solution (NaCI) was injected intraperitoneally. Group II was injected with 34mg/kg aluminum chloride (AlCI3) intraperitoneally. Group III received 400mg/kg ω-3FA for 7days and group IV received both AlCI3 and 400mg/kg ω-3FA for 7days. At the end of the study, blood samples were obtained by cardiac puncture. The findings showed that Al exposure increased serum 8-OHdG and total oxidant status (TOS) levels, as well as ADA activity, which are markers associated with oxidative damage. Conversely, PON and CAT activities, GSH, and total antioxidant status (TAS) levels decreased compared to the control group. Furthermore, Zn and Fe levels decreased as Al levels increased. In conclusion, Al has the capacity to induce oxidative damage and lipid peroxidation, while ω-3 fatty acids may mitigate this damage through a regulatory mechanism. Moreover, ω-3-FA could be used as a therapeutic agent that reduces Al toxicity.

Paraoxonase-1 as a Cardiovascular Biomarker in Caribbean Hispanic Patients Treated with Clopidogrel: Abundance and Functionality.

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases divided into poor and normal responders) were enrolled, along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet reactivity unit (PRU), PON1 abundance by Western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p > 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; p = 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild types (7.90 µU/mL vs. 22.03 µU/mL; p = 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Role of paraoxonase 1 in organophosphate G-series nerve agent poisoning and future therapeutic strategies.

Chemical warfare nerve agents (CWNA) are neurotoxic chemicals unethically used as agents of mass destruction by terrorist outfits and during war. The available antidote against CWNA-mediated toxicity is not sufficiently effective and possesses several limitations. As a countermeasure, paraoxonase 1 (PON1), a catalytic bioscavenger, is being developed as a prophylactic treatment. However, the catalytic activity and substrate specificity of human PON1 are insufficient to be used as a potential antidote. Several laboratories have made different approaches to enhance the CWNA hydrolytic activity against various nerve agents. This review explores the holistic view of PON1 as a potential prophylactic agent against G-series CWNA poisoning, from its initial development to recent advancements and limitations. Apart from this, the review also provides an overview of all available PON1 variants that could be used as a potential prophylactic agent and discusses several possible ways to counteract immunogenicity.

Disease response in rheumatoid arthritis across four biologic therapies associates with improvement in paraoxonase-1 activity and oxylipins

ObjectiveParaoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme, that has been implicated as a biomarker of cardiovascular risk in patients with rheumatoid arthritis (RA). We aimed to investigate how different...

Favourable HDL composition in endurance athletes is not associated with changes in HDL in vitro antioxidant and endothelial anti-inflammatory function.

Given the failure of high-density lipoprotein (HDL) raising therapies to reduce cardiovascular disease risk, attention has turned towards HDL composition and vascular protective functions. In individuals with insulin resistance, exercise interventions recover HDL function. However, the effect of exercise on HDL in otherwise healthy individuals is unknown. This cross-sectional study aimed to measure HDL composition and antioxidant / endothelial anti-inflammatory function in insulin sensitive endurance athlete and healthy control men. HDL was isolated using density gradient ultracentrifugation. HDL composition was measured using microplate assays for apolipoprotein A-I, total cholesterol content and apolipoprotein M. HDL protein composition was measured using nano-liquid chromatography tandem mass spectrometry. HDL subclass distribution was measured by native gel electrophoresis. HDL in vitro antioxidant function was measured by paraoxonase-1 activity assay and anti-inflammatory function assessed in endothelial cells. Compared to controls, endurance athlete HDL had higher apolipoprotein A-1 (1.65 ± 0.62 mg/mL vs 1.21 ± 0.34 mg/mL, p = 0.028) and higher total cholesterol content (1.54 ± 0.33 mmol/L vs 2.09 ± 0.44 mmol/L, p < 0.001). Proteomics revealed higher apolipoprotein A-II, A-IV and D and transthyretin in endurance athlete HDL versus controls. There was no difference observed in in vitro HDL antioxidant or anti-inflammatory functions between controls and endurance athletes. Despite a more favourable composition, endurance athlete HDL did not have higher in vitro antioxidant or anti-inflammatory function. It is possible that HDL has a ceiling of function, i.e. that healthy HDL function cannot be enhanced by endurance exercise.

Effect of hydroalcoholic extract of Tanacetum parthenium on gene expression and paraoxonase 1 enzyme activity: An experimental and molecular dynamic study

Background and aims: Cardiovascular diseases are among the most common causes of death worldwide. The paraoxonase 1 (PON1) enzyme is a main factor in preventing these diseases. This study investigated the effect of hydroalcoholic extract of Tanacetum parthenium plant on the activity and gene expression of PON1. Methods: Forty male rats were divided into 4 groups: a control group, a hyperlipidemic group, and two hyperlipidemic groups that were treated with 400 and 800 mg/kg of hydroalcoholic extract. Arylesterase activity of PON1 and serum triglyceride and cholesterol levels were measured. Moreover, the gene expression of PON1 in the liver tissue samples was measured using real-time PCR. Finally, molecular dynamics studies of apigenin as a main compound in the plant were performed to investigate the activity of PON1 in the simulated environment. Results: Hydroalcoholic extract of T. parthenium decreased serum triglyceride (from 105.8±10.1 to 60.5±21.5 and 50.9±11.2 mg/dL) and total cholesterol (from 97.5±16.8 to 59.6±8.5 and 52.0±9.6 mg/dL) levels, while it increased the activity of arylesterase paraoxonase1 significantly (P&lt;0.001). It also showed a significant (P&lt;0.001) effect on PON1 gene expression. However, the dose of 800 mg/kg was more effective. The results of simulation and molecular dynamics showed that apigenin binds to PON1 with a high affinity and induces changes in the molecular dynamics parameters. Conclusion: The 800 mg/kg of hydroalcoholic extract of T. parthenium can increase the activity of PON1 and its gene expression. It seems that apigenin as one of the most important antioxidant compounds of this plant can increase the activity of this enzyme by direct binding to PON1.

Relationship of paraoxonase-1 and paraoxonase-3 with routine laboratory tests and oxidative stress in type 2 diabetes mellitus

Abstract Objectives We aimed to investigate the relationship between serum paraoxonase-1 (PON1) and paraoxonase-3 (PON3) levels and activities with hemoglobin A1c (HbA1c), serum fasting blood glucose, lipid profile, and oxidative stress in patients with type 2 diabetes mellitus (T2DM). Also, we aimed to examine PON1 and PON3 levels and activities in these patients according to the HbA1c goal in diabetes treatment and PON1192 phenotypes. Methods One hundred forty-one volunteers diagnosed with T2DM participated in this study. Serum PON1 and PON3 levels and activities, total oxidant status (TOS), and total antioxidant status (TAS) were measured. PON1192 phenotypes were determined by using PON1 activities. Also, HbA1c, serum fasting blood glucose, and lipid profile results, which were measured for routine examination on the same day as sample collection, were used for this study. Results There was a positive relationship between arylesterase and lactonase activities and high-density lipoprotein cholesterol (HDL-C), between lactonase activity and TAS, and a negative relationship between PON1 level and TAS in patients with T2DM. Our study also showed that PON3/HDL-C was higher in patients with HbA1c levels ≥7 %. Lactonase activities were higher in patients with PON1Q192Q and PON1Q192R phenotypes than in patients with PON1R192R phenotypes. Conclusions PON1 and PON3 levels and activities alone could not be associated with immediate or long-term blood glucose levels in patients with T2DM. Higher PON3/HDL-C in patients with HbA1c levels ≥7 % may show a protective role of PON3 in defense against higher glucose levels. Also, we found that the PON1192 phenotype can affect serum lactonase activity.

Investigating the Impact of Hibiscus Extracts on Paraoxonase and Antioxidant Activities in Diabetic Rats

Objective: Diabetes mellitus (DM) accelerates oxidative stress beyond its broad effects on metabolic function, which has been linked to various chronic complications. This study investigated the antioxidative and therapeutic potential of Hibiscus syriacus (HSE) and Hibiscus trionum extracts (HTE), focusing on their effects on paraoxonase (PON) and arylesterase enzymes activity in diabetic rat models. Material and Methods: This study evaluated PON and ARE activities in 36 Wistar albino rats divided into the following groups: control (C), C+HSE, C+HTE, Diabetes (D), D+HSE, and D+HTE. The total phenolic content of HSE and HTE was determined using the Folin- Ciocalteu method, and their antioxidant activities were assessed using DPPH and CUPRAC tests. Results: HSE and HTE extracts have demonstrated significant increases in paraoxonase and arylesterase activities, which are crucial for cardiovascular protection and reducing oxidative stress in diabetes. Conclusions: This study highlights the potential of natural extracts in managing oxidative stress-related complications associated with diabetes and underscores the need to integrate such phytotherapeutic agents into broader diabetes care strategies. Future research should focus on confirming these findings in clinical settings and investigating the molecular processes responsible for the observed effects, potentially paving the way for innovative interventions for diabetes management.

Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice.

Bixin (C25H30O4; 394.51 g/mol) is the main apocarotenoid found in annatto seeds. It has a 25-carbon open chain structure with a methyl ester group and carboxylic acid. Bixin increases the expression of antioxidant enzymes, which may be interesting for counteracting oxidative stress. This study investigated whether bixin-rich annatto extract combined with metformin was able to improve the disturbances observed in high-fat diet (HFD)-induced obesity in mice, with an emphasis on markers of oxidative damage and antioxidant defenses. HFD-fed mice were treated for 8 weeks with metformin (50 mg/kg) plus bixin-rich annatto extract (5.5 and 11 mg/kg). This study assessed glucose tolerance, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma, fluorescent AGEs (advanced glycation end products), TBARSs (thiobarbituric acid-reactive substances), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys. Treatment with bixin plus metformin decreased body weight gain, improved insulin sensitivity, and decreased AGEs and TBARSs in the plasma, liver, and kidneys. Bixin plus metformin increased the activities of PON-1, SOD, CAT, and GSH-Px. Bixin combined with metformin improved the endogenous antioxidant defenses in the obese mice, showing that this combined therapy may have the potential to contrast the metabolic complications resulting from oxidative stress.

Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial

BackgroundCardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM.MethodsBefore the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA.ResultsFollowing the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance.ConclusionsA balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality.Trial registrationThe study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.Graphical

Increased oxidative stress biomarkers in central serous chorioretinopathy

Current data suggest that oxidative stress may play an important role in the occurrence of acute central serous chorioretinopathy (CSC), as chorioretinal integrity may be affected by disruption of the patient’s metabolic redox balance, indicating the need for biomarkers. In addition to oxidative stress, high-density lipoprotein (HDL) dysfunction due to dyslipidemia can also lead to many types of physical discomfort. However, little is known about the pathophysiology of the disease resulting from oxidative stress and HDL dysfunction in CSC. The aim of this study was to investigate whether serum oxidative stress and HDL functionality markers have an impact on CSC disease. The case series of this study included 33 consecutive patients with treatment-naïve acute CSC. Thirty-five healthy volunteers of similar age were included in this study as non-CSC controls. Serum samples of the participants were taken and routine lipid values, serum Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidized Low Density Lipoprotein (ox-LDL), and Paraoxonase (PON1) levels were measured quantitatively. Serum oxidative stress index (OSI) was then calculated. Serum Ox-LDL, TOS and OSI levels in the acute CSC group, consisting of patients who had never been treated before and had no other disease, were statistically significantly higher than the control group. Conversely, serum PON1 and TAS levels were lower in CSC than in the control group. The relationship between CSC and deterioration in serum redox balance and decrease in PON1 activity, an important marker of HDL functionality, was demonstrated for the first time through this study. According to the literature, serum levels of these biomarkers, which identify acute/chronic inflammation and oxidative stress, have not been measured before in CSC disease. Finally, it is conceivable that redox balance and HDL functionality may be important in the diagnosis and treatment of the acute phase of CSC.

Impaired HDL antioxidant and anti-inflammatory functions are linked to increased mortality in acute heart failure patients

AimsAcute heart failure (AHF) is typified by inflammatory and oxidative stress responses, which are associated with unfavorable patient outcomes. Given the anti-inflammatory and antioxidant properties of high-density lipoprotein (HDL), this study sought to examine the relationship between impaired HDL function and mortality in AHF patients. The complex interplay between various HDL-related biomarkers and clinical outcomes remains poorly understood. MethodsHDL subclass distribution was quantified by nuclear magnetic resonance spectroscopy. Lecithin–cholesterol acyltransferase (LCAT) activity, cholesterol ester transfer protein (CETP) activity, and paraoxonase (PON-1) activity were assessed using fluorometric assays. HDL-cholesterol efflux capacity (CEC) was assessed in a validated assay using [3H]-cholesterol-labeled J774 macrophages. ResultsAmong the study participants, 74 (23.5 %) out of 315 died within three months after hospitalization due to AHF. These patients exhibited lower activities of the anti-oxidant enzymes PON1 and LCAT, impaired CEC, and lower concentration of small HDL subclasses, which remained significant after accounting for potential confounding factors. Smaller HDL particles, particularly HDL3 and HDL4, exhibited a strong association with CEC, PON1 activity, and LCAT activity. ConclusionsIn patients with AHF, impaired HDL CEC, HDL antioxidant and anti-inflammatory function, and impaired HDL metabolism are associated with increased mortality. Assessment of HDL function and subclass distribution could provide valuable clinical information and help identify patients at high risk.

The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.

Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity. The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity. The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity. The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.

Serum Paraoxonase Activity and Phenotype Distribution in Covid-19 Patients

Objective: For the phenotype classification, it is important to determine the relationship between enzyme activity and the severity of the COVID-19 disease. Reaching significant differences between healthy and infected individuals in terms of genotype and allele distributions may be a guide in the fight against the COVID-19 pandemic. This study, it was aimed to investigate the relationship between serum arylesterase PON1 enzyme activity and disease severity in COVID-19 patients. Methods: Patients over the age of 18 who applied to the Emergency Service between 01-30 April 2020 and were examined with a preliminary diagnosis of COVID-19 were included in the study. In the study, serum PON1 activity was measured in the venous blood of 56 patients diagnosed with Covid-19 disease by either CT or RT-PCR and who have not received any systemic treatment yet. Results: The Arylesterase (AREase) and Paraoxonase (POase) activity levels of the study and control groups were 131.49 ± 52.75 kU/L 142.29 ± 38.82 kU/L, 276.48 ± 220.4 U/L 505.30 ± 301.4 U/L, respectively. It was found that 64.3 % of those infected with Covid-19 had the low-activity PON1 phenotype (p= 0.007) Conclusion: Genetic variability in PON1 may be associated with exposure to or risk of developing the disease. As a result, vaccination of individuals with low activity phenotype can be given priority at the vaccination stage in order to reduce the mortality rate in the fight against the pandemic. Awareness and protection measures of societies with low activity phenotypes can be increased.