Analysis of paraoxonase-1 activity and cupric reducing antioxidant capacity in cerebrospinal fluid of dogs with neurological disorders.

Background: The aim of this pilot study was to assess the potential of cystatin C (Cys C) as a biomarker in NHL and to explore its association with paraoxonase 1 (PON1) activity. Methods: The study included 44 patients with B-cell NHL and 44 healthy subjects. Cys C was measured using the Cobas e 801 analyzer (Roche Diagnostics GmbH, Mannheim, Germany), while PON1and TAS were measured on the ILab 300+ system (Instrumentation Laboratory, Milan, Italy). Results: The serum level of Cys C (mg/L) was significantly higher in NHL patients compared to control subjects :1.03 (0.88–1.24) vs 0.83 (0.78–0.90), P <0.001. The diagnostic performance of Cys C, as assessed by the area under the ROC curve (AUC), was 0.812 (95% CI: 0.732–0.902). The optimal cut-off value for Cys C was 0.870 mg/L with a sensitivity and specificity of 77.1% and 75.6%, respectively. A significant negative correlation was observed between Cys C and PON1 activity (r = –0.42, P = 0.010) in NHL patients. Conclusions: This study underscores the potential of Cys C as a biomarker in NHL. Notably, in the multivariable analysis, Cys C emerged as the only significant predictor of the disease, with each unit increase associated with an approximately threefold higher odds of NHL. Furthermore, the negative correlation between Cys C and PON1, identified for the first time in patients with NHL, may offer valuable insights for future research into the molecular mechanisms underlying this malignancy.

High‐density lipoproteins (HDLs) are deeply implicated in atherosclerosis. HDL, myeloperoxidase (MPO), and paraoxonase‐1 (PON1) form a functional ternary complex where PON1 partially inhibits the MPO activity, and MPO in turn partially inactivates PON1. The activity of MPO is dependent on the concentration of hydrogen peroxide, but the extremely low concentrations of hydrogen peroxide in serums severely constrain MPO activity. PON1 has the activities of organophosphatase, arylesterase, and thiolactonase, but these hydrolase activities are extraneous to antioxidative stress. Thus, we proposed that MPO and PON1 may be involved in atherosclerosis by acting as proteins, rather than enzyme activities. Cholesterol efflux assay, ATP‐binding cassette transporter A1 (ABCA1)–dependent cholesterol efflux, and LCAT activity assay were performed. The effect of MPO, PON1, and serums from the individuals with ASCVD and healthy individuals on cholesterol efflux of human acute monocytic leukemia cell line (THP‐1 cells) was compared. Noncatalytic functions of MPO and PON1 were analyzed using recombinant proteins and neutralizing antibodies. Wound healing assay and tube formation assay were used to analyze noncatalytic functions of MPO and PON1 in modulating the involvement of human umbilical vein endothelial cells (HUVECs). We found that MPO protein decreased the cholesterol efflux; by contrast, PON1 protein increased the cholesterol efflux of THP‐1 cells. Importantly, MPO antibody partially restored cholesterol efflux, but PON1 antibody partially reduced cholesterol efflux of THP‐1 cells. Moreover, ABCA1 was necessary for controlling the involvement of MPO and PON1 in modulating cholesterol efflux of THP‐1 cells. There existed the confrontations between the noncatalytic functions of PON1 and MPO in migration of endothelial cells. Instead, MPO protein enhanced the expression of intercellular adhesion molecule‐1 (ICAM‐1) and E‐selectin of HUVECs; nonetheless, PON1 protein reduced the expression of these adhesion molecules. Of note, PON1 protein was unable to balance out the induction of MPO protein for these adhesion molecules in that the expression of these adhesion molecules generated by the combination of MPO protein and PON1 protein was similar to that of MPO. The activation of THP‐1 cells induced by MPO protein directly impaired in vitro microvascular structure via increasing the expression of IL‐6 and TNFα regulated by NF‐κB p65 of THP‐1 cells. Together, the noncatalytic functions entail MPO and PON in modulating the involvement of monocytes and endothelial cells in atherosclerosis.

Context: Paraoxonase 1 (PON1) is a crucial antioxidant enzyme involved in the hydrolysis of organophosphates and the prevention of oxidative damage to lipoproteins. Objective: This study aimed to purify PON1 using a newly synthesised hydrophobic interaction chromatography gel and to investigate the inhibitory effects of selected emergency cardiac drugs on PON1 activity through in vitro and in silico approaches. Materials and methods: PON1 was purified using a Sepharose-4B-L-tyrosine-6-aminochrysene hydrophobic interaction chromatography gel. The inhibitory effects of deslanoside, digitoxin, esmolol, and adenosine were evaluated via kinetic inhibition assays, molecular docking, molecular dynamics simulations, and MMPBSA calculations. Results: Among the tested compounds, esmolol exhibited the strongest inhibition of PON1 activity (IC50 = 0.131 ± 0.071 μM, Ki = 0.044 ± 0.009 μM) via a competitive mechanism. Molecular docking revealed strong binding affinity of esmolol to the PON1 active site, which was further supported by molecular dynamics simulations over 150 ns. Discussion and conclusion: The findings indicate a potential interaction between commonly used emergency cardiac drugs and PON1, highlighting the importance of evaluating off-target effects on critical metabolic enzymes in cardiovascular therapy.

The increasing elderly population has brought healthy aging into focus. Aging is a multifactorial process characterized by the progressive decline of cellular and tissue functions, largely due to cumulative oxidative stress. Antioxidant-based strategies have therefore gained prominence as potential interventions. This study investigated the protective and therapeutic effects of Squalene (SQ) and Saponin (SP), individually and in combination, on aging-related biomarkers in brain tissue using a D-Galactose (D-Gal)-induced rat model. Forty-eight male Sprague-Dawley rats (200-250g) were randomly divided into eight groups (n = 6). Aging was induced in four groups via intraperitoneal administration of D-Gal (300mg/kg/day) for six weeks. One group received no antioxidants, while others were treated orally with SQ (2.66mL/kg/day), SP (100mg/kg/day), or their combination. Non-aging groups received the same antioxidant treatments without D-Gal. At the end of the intervention, brain tissues were collected for biochemical analysis. Spectrophotometric assessments included Malondialdehyde (MDA), Glutathione (GSH), Nitric oxide derivatives (NOx), Ascorbic acid (AA), and Protein carbonyls (PC). Forkhead Box O3A (FOXO3A), Nuclear factor erythroid 2-related factor 2 (NRF2), Sirtuin 1 (SIRT1), Paraoxonase 1 (PON1), and Klotho were quantified by ELISA. Combined SQ and SP treatment significantly decreased oxidative stress markers (MDA, NOx, PC) and increased antioxidant defenses (GSH, AA) as well as aging-related molecules (FOXO3A, NRF2, SIRT1, PON1, Klotho) (p < 0.05). Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels were also reduced. These findings demonstrate, for the first time, that combined SQ and SP administration can mitigate aging-related oxidative stress and molecular alterations in brain tissue.

Paraoxonase-1 (PON1) is considered a liver-derived antioxidant enzyme circulating bound to high-density lipoproteins, with limited evidence of protein expression in human urothelial tissue. Its role in bladder cancer remains unexplored. Methylthioadenosine phosphorylase (MTAP), an enzyme related to tumor aggressiveness, may interact with oxidative and metabolic stress pathways relevant to tumor progression. We conducted an exploratory study integrating immunohistochemistry, serum biochemistry, and PON1 genotyping in 39 patients with low-grade (LGUC) or high-grade urothelial carcinoma (HGUC). Both PON1 and MTAP showed reduced expression in high-grade tumors, with MTAP reduction being more pronounced and consistent than that of PON1. Serum PON1 concentrations and activities were slightly reduced in HGUC compared with LGUC and controls. Genotype frequencies were similar between patients and controls, and polymorphisms influenced serum enzymatic activity similarly in both groups. Correlations between tissue and serum PON1 did not reach significance, although descriptively low tissue expression aligned with low serum levels. This study provides initial evidence of intratumoral PON1 expression in bladder cancer and suggests that combined PON1/MTAP immunohistochemical assessment may reflect tumor grade and biological behavior. Larger functional studies are needed to clarify their mechanistic and clinical relevance.

Metabolic and functional aspects of high-density lipoproteins (HDL) in familial hypercholesterolemia with or without subclinical coronary atherosclerosis.

Background and Objectives: This narrative review evaluates the potential of Tetranectin (TN) and Paraoxonase-1 (PON1) to bridge the gap between biological pathology and clinical risk stratification by mapping the "Fibrosis-Oxidative Axis". Materials and Methods: A targeted literature search was conducted using Scopus, PubMed, and Google Scholar to identify studies examining the diagnostic and prognostic value of TN and PON1 in heart failure (HF). Evidence was synthesized qualitatively to analyze their roles in structural fibrosis and oxidative defense. Results: Tetranectin functions as a structural indicator, where its dynamics reflect fibroblast activation, extracellular matrix (ECM) deposition, and protein sequestration during tissue remodeling. On the other hand, PON1 serves as a functional metabolic barometer; its reduced activity correlates with systemic oxidative burden, loss of endothelial protection, and pro-inflammatory signaling. These markers capture a bidirectional pathology where oxidative injury drives fibrotic remodeling, which subsequently continue metabolic dysfunction. A dual-biomarker profile is proposed to stratify disease activity: early-stage metabolic stress (reduced PON1) precedes structural changes, while progressive HF involves active fibrosis (altered TN) alongside persistent oxidative injury. Conclusions: The combined assessment of TN and PON1 offers a complementary approach to HF profiling, potentially refining risk stratification beyond hemodynamic parameters. However, clinical implementation requires large-scale validation to address standardization issues and specificity limitations regarding multimorbidity.

Hyperhomocysteinemia is a risk factor of cardiovascular disease (CVD). High-density lipoprotein (HDL) plays an important role in anti-atherosclerosis, with its anti-atherogenic function attributed to HDL-associated proteins such as apolipoprotein A-I (apoA-I) and paraoxonase 1 (PON1). Homocysteine (Hcy) thiolactone modifies lysine residues in proteins, thereby altering their function. Although dysfunction of apoA-I and PON1 has been reported, the precise modification sites and underlying mechanisms have remained unclear. In this study, we aimed to identify Hcy-thiolactone modification sites on apoA-I and PON1. In addition, we sought to clarify the effects of Hcy-thiolactone on PON1 activity and its distribution. Modification sites were analyzed using MALDI-TOF MS. The effects of Hcy-thiolactone on various specimens, including purified proteins, reconstituted HDL (rHDL), HDL collected by ultracentrifugation, and serum samples, were characterized using enzymatic assays measuring three major PON1 activities (arylesterase, paraoxonase, and lactonase) and Western blotting. Our results demonstrated that while some Hcy-thiolactone modification sites were detected on apoA-I, PON1 itself was not directly modified by Hcy-thiolactone. Thiolactonase activity was reduced by Hcy-thiolactone in large HDL particles. Furthermore, a general reduction of PON1 activity and changes in HDL remodeling and distribution were observed in serum samples treated with Hcy-thiolactone. These findings suggest that PON1 dysfunction induced by Hcy-thiolactone is influenced by alterations in HDL remodeling and the enzyme’s distribution on HDL particles. Analysis of PON1’s distribution dynamics under pathological conditions may provide crucial insights into the mechanism of HDL function decline in CVD.

The quality of high-density lipoproteins (HDLs) is characterized by lipid and protein composition, oxidation and glycation extent, and particle size, while the quantity of HDL-C is just the cholesterol amount in HDL. The inverse association between HDL-C and cardiovascular disease (CVD) and hypertension has been well established; however, the U-shaped mortality risk observed from HDL-C underscores that HDL quality and function are equally important. The present cross-sectional study assessed the correlations of serum lipid and glucose profiles, and low-density lipoprotein (LDL) and HDL characteristics, with blood pressure (BP) distribution in ordinary middle-aged Korean participants (n = 50; mean age 47.0 ± 11.7 years; males: n = 25, 49.2.0 ± 11.7 years; females: n = 25, 44.8 ± 11.5 years), with particular focus on HDL quality and its antioxidant capacity. This study observed that serum elevated triglyceride (TG) and glucose levels were directly proportional to elevated systolic BP (SBP) and diastolic BP (DBP), whereas serum total cholesterol (TC), LDL-C, and HDL-C were not correlated with BP. However, HDL-C/TC (%) was negatively associated with SBP (p = 0.036), while TG/HDL-C and glucose/HDL-C ratios were positively associated with both SBP and DBP, suggesting that TG and glucose proportions relative to HDL-C are probable predictors of hypertension. Elevations of TG, oxidation, and glycation in LDL were positively associated with elevations of BP, whereas LDL particle size was negatively correlated with BP. Similarly, elevations of TG and glycation in HDL2 and HDL3 were positively correlated with elevations of BP, while the particle size of HDL2 was negatively correlated with BP. The heightened HDL2-associated paraoxonase (PON) activity and ferric ion reduction ability (FRA) negatively correlated with LDL oxidation and particle size, whereas elevated HDL3-associated PON and FRA activities were inversely related to LDL glycation. An enhanced glycation in HDL2 was negatively correlated with HDL2-associated PON activity and FRA, while an increase in HDL2 particle size was only dependent on the associated PON activity but not on FRA. In conclusion, observational outcomes demonstrated that improved HDL quality and functionality (characterized by large particle size, reduced glycation, and higher FRA and PON activities) were inversely correlated with LDL oxidation, glycation, particle shrinkage, and the risk of hypertension.

Intrinsic Factors Influencing Simvastatin and Simvastatin Acid Pharmacokinetics: Age‐Related Studies in Thai Adults and Cross‐Population Comparisons

Introduction Oxidative stress is a key component of maternal–fetal physiology and varies with the mode of delivery. Labor induces hypoxia–reoxygenation cycles that elevate reactive oxygen species, whereas elective cesarean section (CS) occurs in a controlled metabolic environment. Emergency CS combines labor-related hypoxia with acute surgical stress. Comprehensive comparisons of maternal and cord oxidative profiles across all delivery modes remain limited. Methods This prospective observational study included 126 term singleton pregnancies categorized as elective CS (n = 46), emergency CS (n = 39), or vaginal delivery (n = 41). Maternal blood was collected immediately before delivery and cord blood after birth. Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and paraoxonase-1 (PON-1) activity were measured using automated RelAssay methods; OSI was calculated as (TOS/TAS)×100. Neonatal outcomes included Apgar scores and NICU admission. Group comparisons used ANOVA, Kruskal–Wallis, and chi-square tests, with ANCOVA adjusting for gestational age, maternal weight, diabetes, hypothyroidism, preeclampsia, and ASA use. Results Baseline characteristics were comparable. Emergency CS had lower Apgar-1 scores and higher NICU admission. Maternal OSI (p = 0.002) and PON-1 (p = 0.004) differed significantly, with elective CS showing the most favorable profile. Cord TOS (p < 0.001), OSI (p < 0.001), and PON-1 (p = 0.001) were also highest in emergency CS. Delivery mode independently predicted maternal OSI and PON-1, and cord TOS, OSI, and PON-1 (all p < 0.01). Discussion The pronounced oxidative shifts observed in emergency CS likely reflect the cumulative impact of prolonged labor, fetal distress, and abrupt surgical intervention. Elective CS, by avoiding labor-induced hypoxia and metabolic exhaustion, preserves a more balanced maternal–fetal redox environment. The parallel maternal and cord responses underscore the sensitivity of the fetoplacental unit to intrapartum oxidative changes. These findings clarify mechanistic differences between delivery modes and highlight redox status as a potential peripartum biomarker. Conclusion Elective CS preserves maternal–fetal redox homeostasis, whereas emergency CS results in significant oxidative disruption and poorer neonatal adaptation. These findings support the potential use of oxidative stress markers as adjunct indicators of acute intrapartum stress when interpreted alongside established clinical parameters.

ObjectiveTo investigate the effects of combined oral contraceptives (COCs) and metformin treatment on the lactonase activity and status of paraoxonase 1 (PON1), and oxidative stress levels in patients with polycystic ovary syndrome (PCOS) and insulin resistance (IR).DesignA prospective, self-controlled study.MethodsSixty patients diagnosed with PCOS and IR underwent three months of comprehensive therapy, including lifestyle modification, oral metformin (1000–1500 mg/day), and a COC (3 mg drospirenone and 20 µg ethinyl estradiol). Clinical data and blood samples were collected at baseline and after three months of treatment. PON1 levels, lactonase activity, and normalized lactonase activity (NLA), along with PON1 Q192R and C-108T genetic polymorphisms, oxidative stress markers, hormonal profiles, and metabolic parameters, were analyzed.ResultsAfter treatment, significant decreases were observed in body mass index (BMI), Global Acne Grading System scores, androstenedione, fasting insulin, the homeostasis model assessment of insulin resistance index, and total antioxidant capacity (P < 0.05). In contrast, serum PON1 lactonase activity, apolipoprotein (apo)A1, triglycerides, and 2-h glucose levels were significantly increased (P < 0.05). Spearman’s correlation analysis showed that lactonase activity and PON1 status were correlated with serum apoA1, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total oxidant status, and the oxidative stress index (P < 0.05). Moreover, the group with improved NLA showed higher PON1 lactonase activity and HDL-C levels, whereas the group without improved NLA showed higher PON1 levels after treatment.ConclusionTreatment with COCs and metformin enhanced the antioxidant capacity of circulating HDL and improved BMI, glycolipid metabolism, IR, and hyperandrogenism in patients with PCOS and IR.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.html?proj=152682, identifier ChiCTR2200057114.

Mastitis remains a prevalent and economically detrimental disease within the dairy industry, profoundly affecting animal welfare, milk quality, and overall production output. Nowadays, Somatic Cell Count (SCC) is widely recognized as the gold-standard indicator for the detection of mastitis; however, its limitations in pathogens discrimination and the lack of early-stage characterization of mastitis highlight the need for complementary diagnostic approaches. This review synthesizes recent research into the development and validation of novel biomarkers for the early and accurate identification of mastitis in dairy cows. The investigation encompasses a range of biological molecules for improving mastitis diagnosis. Biomarkers such as lactoferrin (LTF), β-defensin 4 (DEFB4), vitronectin, paraoxonase 1 (PON1), and N-acetyl-β-D-glucosaminidase (NAGase) show promise in distinguishing between cows not susceptible and cows susceptible to mastitis. Concurrently, nucleic acid-based biomarkers are emerging as a particularly promising frontier. While mitochondrial DNA (mtDNA) has demonstrated insufficient specificity, microRNAs (miRNAs) are gaining attention as highly stable and sensitive indicators of intramammary inflammation, potentially enabling the detection of subclinical infections before they become clinically apparent. Despite these advances, significant challenges related to specificity, reliability, and cost-effectiveness currently hinder the widespread practical application of any single biomarker. Therefore, future research should be directed towards the validation of a synergistic panel of multiple biomarkers to improve mastitis management in dairy cow farms.

To compare the systemic inflammatory and oxidative stress responses after elective ovariectomy via open surgery (OPEN) or laparoscopy (LAP) in anestrus bitches. Prospective, blinded, randomized clinical trial. Animals A total of 26 healthy bitches. A total of 26 healthy bitches in anestrus were randomly assigned to undergo either LAP or OPEN ovariectomy (n = 13 per group). Blood samples were collected at four timepoints (preoperative-Tpre, 2 h-T2, 24 h-T24, and 7 days postoperative-T7) for quantification of interleukin-6 (IL-6) and paraoxonase-1 (PON-1), biological antioxidant potential (BAP), and reactive oxygen metabolites (d-ROMs). IL-6 levels were higher in the OPEN group at Tpre, T24 and T7, while the LAP group exhibited a transient peak at T2 with a return to baseline by T7. PON-1 levels decreased in both groups at T2 but remained lower in the LAP group at T24 and T7. d-ROM levels were higher in the OPEN group, with an increase through T7, whereas the LAP group showed only a transient peak at T24. BAP levels increased in the OPEN group, but not in the LAP group by T7. LAP ovariectomy induced a milder and more transient inflammatory and oxidative response compared to OPEN surgery in bitches, likely due to reduced surgical trauma. This study included only animals in anestrus. This is the first application of both canine-specific biomarkers of inflammation and canine-validated biomarkers of oxidative stress to compare techniques of elective canine spaying. These findings suggest that minimally invasive ovariectomy attenuates inflammatory and oxidative stress responses compared to OPEN technique in dogs.

Disruption of HDL antioxidant properties in children and adolescents with obesity.

Anti-biofilm efficiency and substrate specificity of recombinantly produced human paraoxonases.

Protective effects of oleuropein isolated from Olea europaea L. on renal ischemia/reperfusion injury in rats: Insights into antioxidant, and anti-apoptotic pathways.

Residual cardiovascular risk is tracked by apolipoprotein B in coronary patients with elevated serum triglyceride levels: the ESC EORP EUROASPIRE IV survey.

Diabetes mellitus (DM) leads to renal damage through oxidative stress. Carvacrol (CAR), a monoterpenoid phenol, possesses anti-inflammatory and antioxidant properties. We investigated the potential effects of CAR on histological, gene expression, and biochemical parameters in a rat model of DM. Four groups were created: group 1, control; group 2 (n = 9), DM; group 3 (n = 9), DM + dimethyl sulfoxide (DMSO); and group 4 (n = 9), DM + CAR. DM was created by injecting streptozotocin (STZ). CAR (20 mg/kg) was prepared through dissolution in 0.1% DMSO. CAR and 0.1% DMSO were administered daily for 4 weeks to groups 4 and 3, respectively. At the end of this study, urea, creatinine, paraoxonase-1 (PON-1), and arylesterase (ARES) were measured in serum samples. Histopathological changes and expression of Nuclear factor erythroid 2–related factor 2 (Nrf-2) in renal tissues were assessed. Immunohistochemical(ihc) staining and RT-qPCR analysis were performed to evaluate apoptosis, focusing on Bax and Bcl-2gene expression. Masson’s trichrome(MT) staining and RT-qPCR analysis of COL1A1 and COL3A1 mRNA levels were used to assess fibrosis. Increased urea and creatinine levels in DM were significantly decreased after CAR administration. CAR application also improved reduced levels of PON 1 and ARES, which are associated with diabetes. Both immunohistochemistry and RT-qPCR analyses revealed that CAR therapy mitigated the diabetes-induced elevation in Bax and reduction in Bcl-2 expression. CAR treatment improved histopathological findings and renal Nrf-2 immunofluorescence(if) intensity. Furthermore, gene expression analysis demonstrated that COL1A1 and COL3A1 were upregulated in DM, while CAR administration downregulated them. In conclusion, CAR has a protective role in decreasing renal impairment linked to DM by regulating Bax and Bcl-2 levels and rectifying histological damage.