Antioxidant Paraoxonase Research Articles

A review on oxidative stress in organophosphate-induced neurotoxicity.

Acetylcholinesterase inhibition, the principal mechanism of acute organophosphorus compound toxicity, cannot explain neuropsychiatric symptoms occurring after exposure to low organophosphate concentrations causing no cholinergic symptoms. Organophosphate-triggered oxidative stress has increasingly come into focus, occurring when the action of reactive oxygen species, generated from free radicals, is not compensated by antioxidant free radical scavengers. Being nucleophilic, organophosphates can easily accept an electron, thereby generating free radicals. Organophosphates inhibit the antioxidant paraoxonase, and reactive oxygen species are produced during organophosphate metabolism. Organophosphates disrupt the function of mitochondria, the principal source of free radicals. Organophosphates also induce neuroinflammation, which generates reactive oxygen species, and reactive oxygen species in turn stimulate neuroinflammation. Markers of reactive oxygen species are elevated in vitro and in vivo after exposure to organophosphates and in individuals professionally exposed to organophosphates. This most probably contributes to the pathogenesis of the intermediate syndrome and chronic organophosphate-induced neuropsychiatric disorders occurring in patients after organophosphate exposure. Evidence for beneficial effects of antioxidants in organophosphate poisoning is discussed.

Obeticholic acid's effect on HDL function in MASH varies by diabetic status.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL-the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.

Potential biomarkers of ASD a target for future treatments: oxidative stress, chemokines, apoptotic, and methylation capacity.

The study aimed to assess the effect of these biomarkers on a sample of children with autism spectrum disorder (ASD) to help in early diagnosis and intervention. A total of 71 autistic patients and 65 normal controls were enrolled in this study. Their ages ranged from 5 to 11 years (mean±SD 7.47±3.81). Childhood Autism Rating Scale (CARS) was assessed for all patients and controls. Assessment of oxidative stress, monocyte chemoattractant protein-1, B-cell lymphoma 2, S-adenosylhomocysteine (SAH), and apelin was performed. Oxidative stress (oxidized low-density lipoprotein and malonaldehyde) increased while antioxidant paraoxonase (PON) decreased. Monocyte chemoattractant protein-1, B-cell lymphoma 2, and S-adenosylhomocysteine (SAH) were all elevated whereas, apelin was downregulated. It is important to note that many factors that may contribute to ASD including genetic factors. To open the door for novel treatment strategies, it is still necessary to precisely understand how oxidative stress, chemokines, apoptosis, and methylation capability affect the metabolism of people with ASD.

Relationship between blood antioxidant paraoxonase-1 and the offspring yield in Hair goats

Relationship between blood antioxidant paraoxonase-1 and the offspring yield in Hair goats

Effect of Sphingomyelinase-Treated LDLs on HUVECs.

Low-density lipoproteins (LDLs) exert a key role in the transport of esterified cholesterol to tissues. Among the atherogenic modifications of LDLs, the oxidative modification has been mainly investigated as a major risk factor for accelerating atherogenesis. Since LDL sphingolipids are also emerging as important regulators of the atherogenic process, increasing attention is devoted to the effects of sphingomyelinase (SMase) on LDL structural and atherogenic properties. The aims of the study were to investigate the effect of SMase treatment on the physical-chemical properties of LDLs. Moreover, we evaluated cell viability, apoptosis, and oxidative and inflammatory status in human umbilical vein endothelial cells (HUVECs) treated with either ox-LDLs or SMase-treated LDLs (SMase-LDLs). Both treatments were associated with the accrual of the intracellular ROS and upregulation of the antioxidant Paraoxonase 2 (PON2), while only SMase-LDLs induced an increase of superoxide dismutase 2 (SOD2), suggesting the activation of a feedback loop to restrain the detrimental effects of ROS. The increased caspase-3 activity and reduced viability observed in cells treated with SMase-LDLs and ox-LDLs suggest a pro-apoptotic effect of these modified lipoproteins on endothelial cells. Moreover, a strong proinflammatory effect of SMase-LDLs compared to ox-LDLs was confirmed by an increased activation of NF-κB and consequent increased expression of its downstream cytokines IL-8 and IL-6 in HUVECs.

Serum Paraoxonase-1 Activity in Prostate Cancer Patients Treated with Brachytherapy as a Measure of Irradiation Efficacy

We investigated changes in the activity of antioxidant paraoxonase-1 (PON1) in patients with prostate cancer (PCa) undergoing radiotherapy (RT), as well as the relationship of the PON1 activity with the degree of PCa advancement. We included 84 men with PCa. Blood samples were obtained before irradiation and after the completion of RT. The control group was composed of 60 healthy men. There was no significant difference in the PON1 activity between the control group and patients pre-radiotherapy. Irradiation was associated with a significant decrease in the PON1 activity; thus, it could be a measure of the efficacy of RT. No significant correlations between the PON1 activity and Gleason score, prostate volume, BMI (body mass index), or adipose tissue thickness were found. However, there was a positive correlation between the PON1 activity and the PSA concentration in the group of PCa patients.

Associations between myeloperoxidase and paraoxonase-1 and type 2 diabetes in patients with ischemic heart disease

BackgroundThe phrase “dysfunctional high-density lipoprotein” has been developed in the literature to describe the particle which loses its basic role- anti-oxidative and anti-inflammatory activity. In this porcess, the significance of enzymes- pro-oxidant myeloperoxidase (MPO) and antioxidant paraoxonase-1 (PON-1) from the perspective of HDL-C function has been noted.AimsThe objective of this study was to analyze the associations between two enzymes –MPO and PON-1 and type 2 diabetes (T2DM) in patients with ischemic heart disease (IHD).MethodsAn observational cross-sectional study including 70 patients with IHD of whom 35 had also T2DM, and 35 had no T2DM. Laboratory tests (MPO, PON-1, fasting glucose, glycated hemoglobin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and high-sensitivity C-reactive protein) were performed.ResultsThe study revealed a significant difference in the serum concentration of the enzymes between patients with IHD with and without T2DM. Our results showed increased MPO concentration levels in diabetic patients. The analysis also revealed that T2DM is independently associated with an increase in MPO levels. Simultaneously, a decrease in PON-1 levels was observed in patients with T2DM. The study also revealed that T2DM is independently associated with a decrease in PON-1 levels.ConclusionsIn patients with type 2 diabetes the profile of enzymes involved in high-density lipoprotein metabolism in patients with IHD is worse than in patients without T2DM. The increase in the levels of MPO, an enzyme with oxidative and atherogenic properties and on a decrease in PON-1 levels, an enzyme with antioxidant and atheroprotective properties is observed.

Evaluation of paraoxonase activity and association with serum advanced glycation end products as reliable markers of oxidative stress in Hashimoto's thyroiditis.

Oxidative stress has been implicated in the pathogenesis of autoimmune thyroiditis, also referred to as Hashimoto's thyroiditis (HT), and several biomarkers have been measured to evaluate the impact and clinical relevance of oxidative stress in this setting. Recently, advanced glycation end products (AGEs) have been proposed as reliable markers of oxidative stress in HT. In the present study, we investigated the relationship of AGEs with antioxidant paraoxonase (PON-1) activity as potential combined markers of oxidative stress. We measured the levels of AGEs, and advanced oxidation protein products (AOPPs) and PON-1 activity by spectrophotometric methods, in the serum of 40 HT patients (36 F; mean age 35.4 ± 11.5 yr) and 38 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy. Serum levels of AGEs were significantly higher (median 378 vs 290 AU/g protein; P<0.001), while PON1 activity was significantly lower (median 165 vs 201 U/L; P<0.05) in HT patients compared to controls: the two parameters were inversely correlated (P<0.01), clearly indicating a pro-oxidant imbalance in HT patients. At stepwise regression analysis, TPOAb positivity was an independent predictor of both PON-1 activity (P = 0.002) and AGEs levels (P = 0.000). Increased formation and accumulation of AGEs contribute to enhanced oxidative stress, along with a decrease in PON-1 activity in HT. As a consequence, AGEs levels and alteration in PON 1 may serve as useful markers for monitoring the levels of oxidative stress in this disorder.

The effect of Paraoxonase gene polymorphisms and paraoxonase enzyme activity on Non-Hodgkin lymphoma

Non-Hodgkin Lymphoma (NHL) is a malignant lymphoproliferative disease. Antioxidant paraoxonase enzyme (PON1) has a vital role in the elimination of potential carcinogenic organophosphate molecules. The polymorphisms in the PON1 gene, especially Q192R and L55M, may affect negatively the activity and synthesis of PON1 enzyme. The aim of this study was to evaluate the effect of these polymorphisms together with PON1 enzyme activity on NHL. We surveyed these polymorphisms together with PON1 enzyme activity in 93 patients with NHL and in 93 healthy individuals by real-time polymerase chain reaction (RT-PCR) and spectrophotometer. Although carrying the M and R alleles of L55M and Q192R polymorphisms increases the risk of NHL, they were not significant. Furthermore, the NHL patients carrying 192 R allele had significantly lower enzyme activity than controls having same allele (P = 0.025). This research is the first study worldwide investigating the effect of Q192R and L55M polymorphisms on PON1 enzyme activity in NHL disease. The risk of developing NHL may be further increased in individuals with low enzyme activity having R risk allele of the Q192R polymorphism. The present study suggests that these polymorphisms in NHL disease should be analyzed together with PON1 enzyme activity in larger populations. Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2022.2052315 .

Evaluation of Oxidative Stress and Inflammatory Biomarkers Pre and Post-Treatment in New Diagnosed Atherosclerotic Patients

ABSTRACT Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. It is characterized by lipid accumulation in the arterial wall, increased hyperlipidemia, oxidative stress, lipid peroxidation, and protein oxidation. Our study included 45 patients ages of 40–60 and 45 healthy volunteers with similar demographic characteristics without any chronic disease as well. Fasting plasma glucose, BUN, creatinine, LDL-cholesterol, HDL-cholesterol, triglyceride, total cholesterol, HbA1c, and C-reactive protein (CRP) levels were measured using commercial kits by autoanalyzer. The oxidative stress biomarkers total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), native thiol (NT), catalase (CAT), paraoxonase (PON1), and arylesterase (ARES) enzyme activities were measured using photometric methods. The inflammatory biomarkers interleukin 1 beta (IL-1β), tumor necrosis factor-α (TNF-α), presepsin (PSPN), and raftlin (RFTN1) levels were measured with ELISA Kits. Oxidative stress index (OSI) and disulfide (DIS) were calculated. The clinical, biochemical biomarkers such as BUN, creatinine, HDL, LDL, total cholesterol, triglyceride, and CRP levels were found to be higher than the control group and lower post-treatment compared to the pre-treatment group (p <0.001). The oxidative stress parameters, TOS, OSI, and DIS levels were found to be higher than the control group, and the levels before the treatment were statistically significantly higher than after the treatment (p < 0.001).Antioxidant biomarkers TAS, TT, and NT levels were low in the patient group. Inflammatory biomarkers were highest before treatment and decreased with treatment. Oxidative stress and inflammation, which increased in atherosclerosis patients may guide disease prognosis and treatment strategies.

Serum Paraoxonase-1 Activity and the Risk of Prostate Cancer Recurrence in Patients Treated with Radiotherapy.

The antioxidant paraoxonase-1 (PON1) may be involved in the response to radiation-induced oxidative stress and possibly prevent cell apoptosis. The correlation of PON1 with the risk of cancer recurrence after radiotherapy (RT) is not yet explored. We investigated changes in the activity of PON1 in patients with prostate cancer (PCa) undergoing RT, and the relation of PON1 activity to the risk of recurrence after RT. We included 56 men with PCa. Blood samples were obtained before irradiation and after the completion of RT. Patients were followed for an average of 51.2 months. Each case of biochemical recurrence was confirmed with biopsy. The control group was composed of 60 healthy men. There was no significant difference in PON1 activity between the control group and patients pre-radiotherapy. Irradiation was associated with a significant decrease in PON1 activity. Patients with PCa recurrence had significantly higher serum PON1 activity than those recurrence-free, both before and after RT. PON1 activity was a predictor of PCa recurrence, with sensitivity over 80% and specificity over 64%. Our results suggest that PON1 activity may be a predictor of PCa recurrence risk after RT. Studies with a larger number of patients and longer follow-up are needed to confirm this hypothesis.

Deep Sea Water-Dissolved Organic Matter Intake Improves Hyperlipidemia and Inhibits Thrombus Formation and Vascular Inflammation in High-Fat Diet Hamsters.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by oxidative stress, inflammation and lipid deposition within liver cells, and is subsequently contributing to cardiovascular diseases such as atherosclerosis. Deep sea water (DSW) is characterized by its clearance and abundant nutrients with antioxidant and anti-inflammatory activity to confer therapeutic potential. We aimed to explore the therapeutic capability of our prepared multi-filtration DSW-dissolved organic matter (DSW-DOM) on high-fat diet-induced hyperlipidemia and endothelial dysfunction in hamsters. A high-fat/high-cholesterol diet led to increased oxidative stress, including blood reactive oxygen species (ROS), plasma malondialdehyde (MDA) and hepatic CYP2E1 expression; an increased hyperlipidemic profile and SREBP 1-mediated fatty liver; promoted NFκB p65-mediated hepatic inflammation; triggered PARP-mediated hepatic apoptosis; and enhanced endothelial intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (VWF)-mediated atherosclerosis associated with the depressed hepatic antioxidant Paraoxonase 1 (PON1) expression. The DSW-DOM-enriched 1295 fraction, with strong H2O2 scavenging activity, efficiently reduced several oxidative stress parameters, the lipid profile, inflammation, and apoptosis, possibly through the PON1-mediated antioxidant capability. Furthermore, DSW-DOM treatment significantly decreased the endothelial ICAM-1 and VWF expression, subsequently leading to the elongation of time to occlusion of FeCl3-induced arterial thrombosis and to the inhibition of FeCl3-induced fluorescent platelet adhesion to mesentery arterioles in the high-fat diet. Based on the above results, our data suggest that DSW-DOM intake via antioxidant defense mechanisms confers protective effects against high-fat diet-enhanced, oxidative stress-mediated hyperlipidemia, and endothelial dysfunction evoked atherosclerosis by downregulating oxidative injury, lipogenesis, inflammation and apoptosis.

Evidence of Paraoxonases 1, 2, and 3 Expression in Human Ovarian Granulosa Cells.

Increasing evidence suggests that the antioxidant paraoxonase proteins, PON1, PON2, and PON3, have a role in reproduction and may be synthesized by ovarian cells. The aim of this work was to investigate whether human ovarian granulosa cells (GC) express paraoxonases 1, 2, and 3 (PON1, PON2, and PON3) at both the transcriptional and protein levels. Cells were purified from follicle samples of women undergoing ovarian stimulation at oocyte retrieval. We analyzed mRNA by polymerase chain reaction using specific primers for the different variants and quantified the proteins by Western blot using commercially available human recombinant PON proteins as standards. The protein subcellular distribution was determined by immunofluorescence and confocal microscopy and the cell cycles by flow cytometry. Thymidine was used for cellular synchronization at G1/S. Human hepatoma HepG2 and immortalized granulosa COV434 cell lines were used to optimize methodologies. mRNAs from PON1, the two variants of PON2, and PON3 were detected in GC. The cells actively secreted PON1 and PON3, as evidenced by the protein detection in the incubation medium. PON1 and PON3 were mainly distributed in the cytoplasm and notably in the nucleus, while PON2 colocalized with mitochondria. Subcellular nucleo-cytoplasmic distribution of PON1 was associated with the cell cycle. This is the first evidence describing the presence of mRNAs and proteins of the three members of the PON family in human ovarian GC. This study provides the basis of further research to understand the role of these proteins in GC, which will contribute to a better understanding of the reproduction process.

Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis.

Background Long-term hematopoietic stem cells (LT-HSCs) reside in bone marrow niches with tightly controlled reactive oxygen species (ROS) levels. ROS increase results into LT-HSC differentiation and stem cell exhaustion. Paraoxonase 2 (PON2) has been shown to be important for ROS control. Objectives We investigate the effects of inactivation of the PON2 gene on hematopoietic cell differentiation and activity. Methods and Results In young mice with inactivated Pon2 gene (Pon2−/−, <3 months), we observed an increase of LT-HSCs and a reduced frequency of progenitor cells. In competitive transplantations, young Pon2−/− BM outcompeted WT BM at early time points. ROS levels were significantly increased in Pon2−/− whole BM, but not in Pon2−/− LT-HSCs. In more differentiated stages of hematopoiesis, Pon2 deficiency led to a misbalanced erythropoiesis both in physiologic and stress conditions. In older mice (>9 months), Pon2 depletion caused an increase in LT-HSCs as well as increased levels of granulocyte/macrophage progenitors (GMPs) and myeloid skewing, indicating a premature aging phenotype. No significant changes in ROS levels in old Pon2−/− LT- and short-term (ST-) HSCs were observed, but a significant reduction of spontaneous apoptotic cell death was measured. RNA-seq analysis in Pon2−/− LT-HSCs identified overrepresentation of genes involved in the C-X-C chemokine receptor type 4 (Cxcr4) signaling, suggesting compensatory mechanisms to overcome ROS-mediated accelerated aging in hematopoietic progenitor cells. Conclusions In summary, our current data indicate that PON2 is involved in the regulation of HSC functions.

Antioxidant paraoxonase 1 activity in children with celiac disease. Impact of gluten free diet

Background and Aims: There is evidence, that celiac disease (CD) could be associated with non-traditional atherogenic risk factors. High density lipoproteins (HDL) constitute the only antiatherogenic fraction, being the inhibition of low density lipoprotein (LDL) oxidation one of its main functions. This capacity depends on different HDL-associated components, such as the antioxidant enzyme paraoxonase (PON1). To assess the relationship between CD and the activity of PON1 in recently diagnosed children compared to healthy controls, and the effect of gluten-free diet (GFD).

An Increased Plasma Level of ApoCIII-Rich Electronegative High-Density Lipoprotein May Contribute to Cognitive Impairment in Alzheimer's Disease.

High-density lipoprotein (HDL) plays a vital role in lipid metabolism and anti-inflammatory activities; a dysfunctional HDL impairs cholesterol efflux pathways. To understand HDL’s role in patients with Alzheimer’s disease (AD), we analyzed the chemical properties and function. HDL from AD patients (AD-HDL) was separated into five subfractions, H1–H5, using fast-protein liquid chromatography equipped with an anion-exchange column. Subfraction H5, defined as the most electronegative HDL, was increased 5.5-fold in AD-HDL (23.48 ± 17.83%) in comparison with the control HDL (4.24 ± 3.22%). By liquid chromatography mass spectrometry (LC/MSE), AD-HDL showed that the level of apolipoprotein (apo)CIII was elevated but sphingosine-1-phosphate (S1P)-associated apoM and anti-oxidative paraoxonase 1 (PON1) were reduced. AD-HDL showed a lower cholesterol efflux capacity that was associated with the post-translational oxidation of apoAI. Exposure of murine macrophage cell line, RAW 264.7, to AD-HDL induced a vibrant expression of ganglioside GM1 in colocalization with apoCIII on lipid rafts alongside a concomitant increase of tumor necrosis factor-α (TNF-α) detectable in the cultured medium. In conclusion, AD-HDL had a higher proportion of H5, an apoCIII-rich electronegative HDL subfraction. The associated increase in pro-inflammatory (apoCIII, TNF-α) components might favor Amyloid β assembly and neural inflammation. A compromised cholesterol efflux capacity of AD-HDL may also contribute to cognitive impairment.

Do PON1–Q192R and PON1–L55M polymorphisms modify the effects of hypoxic training on paraoxonase and arylesterase activity?

BackgroundLow levels of antioxidant paraoxonase 1 (PON1) enzyme activity, PON1–Q192R polymorphism (a glutamine (Q) to arginine (R) substitution at position 192), PON1–L55M polymorphism (a leucine (L) to methionine (M) substitution at position 55), and oxidized low-density lipoprotein (oxLDL) are risk factors for coronary heart disease. Aerobic exercise improves PON1 activity, but the effects of hypoxic exercise are yet unclear. The aim of this study was to determine the effects of hypoxic underwater rugby training on PON1 activity and oxLDL levels and the role of the mentioned polymorphisms. MethodsSerum PON1 and arylesterase activities (ARE), PON1, PON3, and oxLDL protein levels (by using the enzyme-linked immunosorbent assays) were determined in an athletic group (42 trained male underwater rugby players; age = 21.7 ± 4.2 years, mean ± SD) and a control group (43 sedentary men; age = 23.9 ± 3.2 years). The polymorphisms were determined from genomic DNA samples. ResultsPON1 activity (25.1%, p = 0.052), PON3 (p < 0.001), and oxLDL (p < 0.001) of the athletic group, including most genotype groups, were higher than those of the control group. In comparison to the controls, PON1 activity levels (p = 0.005) of the PON1–Q192R homozygote QQ genotype group and PON1 activity levels (30%, p = 0.116) of the PON1–L55M homozygote LL genotype group were higher, whereas ARE activity values of athletic R allele carrier (Rc = QR + RR) (p = 0.005) and LL group (p = 0.002) were lower than the control genotype groups related to their polymorphisms. ConclusionHypoxic training can cause (1) significant oxidative stress, including oxLDL, and an antioxidant response (increase in PON1 activity and PON3), (2) differences in the activity of PON1 and ARE, which are modified by PON1–Q192R and PON1–L55M polymorphisms, respectively, and (3) improvements in PON1 activity of QQ and LL groups. However, hypoxic training can cause a disadvantage of LL and Rc groups for ARE.

Arylesterase Activity of HDL Associated Paraoxonase as a Potential Prognostic Marker in Patients With Sepsis and Septic Shock-A Prospective Pilot Study.

Background: High-density lipoprotein (HDL) plays an essential role in the immune system and shows effective antioxidative properties. We investigated correlations of lipid parameters with the sequential organ failure assessment (SOFA) score and the prognostic association with mortality in sepsis patients admitted to intensive care unit (ICU).Methods: We prospectively recruited consecutive adult patients with sepsis and septic shock, according to sepsis-3 criteria as well as non-sepsis ICU controls.Results: Fifty-three patients with sepsis (49% with septic shock) and 25 ICU controls without sepsis were enrolled. Dyslipidemia (HDL-C < 40 mg/l) was more common in sepsis compared to non-sepsis patients (85 vs. 52%, p = 0.002). Septic patients compared to controls had reduced HDL-C (14 vs. 39 mg/l, p < 0.0001), lower arylesterase activity of the antioxidative paraoxonase of HDL (AEA) (67 vs. 111 mM/min/ml serum, p < 0.0001), and a non-significant trend toward reduced cholesterol efflux capacity (9 vs. 10%, p = 0.091). We observed a strong association between higher AEA and lower risk of 28-day [per 10 mM/min/ml serum increase in AEA: odds ratio (OR) = 0.76; 95% CI, 0.61–0.94; p = 0.01) and ICU mortality (per 10 mM/min/ml serum increase in AEA: OR = 0.71, 95% CI, 0.56–0.90, p = 0.004) in the sepsis cohort in univariable logistic regression analysis. AEA was confirmed as an independent predictor of 28-day and ICU mortality in multivariable analyses. AEA discriminated well-regarding 28-day/ICU mortality in area under the receiver operating characteristic curve (AUROC) analyses. In survival analysis, 28-day mortality estimates were 40 and 69% with AEA ≥/< the 25th percentile of AEA's distribution, respectively (log-rank p = 0.0035).Conclusions: Both compositional and functional HDL parameters are profoundly altered during sepsis. In particular, the functionality parameter AEA shows promising prognostic potential in sepsis patients.

Evaluation of paraoxonase-1 enzyme activity and oxidative stress relations in malignant mesothelioma cases

BACKGROUND: Malignant pleural mesothelioma (MPM) is the most common cancer in the pleura and highly aggressive with a very poor prognosis. Asbestos, known as a carcinogenic mineral with fiber structures, is the main cause of MPM formation. Exposure to asbestos causes an increase in reactive oxygen species, deficiency of antioxidant enzyme levels, and DNA damage. As a result of asbestos pathogenesis, all of these changes cause pulmonary fibrosis, pleural diseases, and malignancies. The endogenous antioxidant paraoxonase-1 (PON-1) is a calcium-dependent esterase involved in the hydrolysis of lipid peroxides, and PON-1 has been shown to have protective properties in oxidative stress and inflammatory diseases in various studies. OBJECTIVE: The study aimed to examine the relationship of MPM with PON-1 enzyme activity and oxidative status using total oxidant status (TOS) and total antioxidant status (TAS). MATERIALS AND METHODS: The study population was formed of 33 retrospectively examined mesothelioma patients as MPM group and 33 age- and sex-matched healthy individuals as controls. PON-1 activity was measured spectrophotometrically by enzyme-linked immunosorbent assay method. Total antioxidant and oxidant status was determined using Rel Assay Diagnostics kit. Oxidative stress index (OSI) was estimated as the ratio of the TOS to the TAS levels. RESULTS: In the present study, PON-1, TOS, TAS, and OSI levels were adjusted by comorbidity and smoking. The results indicated that TOS and OSI of MPM patients increased compared to healthy controls (P CONCLUSION: These results suggested that oxidative stress occurring as a result of inhalation of asbestos fibers may reduce the level of PON-1.

Ovarian stimulated cycles reduce protection of follicular fluid against free radicals

Controlled ovarian hyperstimulation cycle with exogenous gonadotropins (COH) is associated with clinical complications. The aim of this work was to determine whether COH alters the physiological antioxidant status of follicular fluid in women with no reproductive dysfunction, compared to the natural cycle (NC). In this longitudinal study, forty-one women (oocyte donors) consecutively underwent NC and COH. Follicular fluid was collected at oocyte retrieval and different redox biomarkers were determined: total antioxidant activity (TAA), oxygen radical absorbance capacity (ORAC), nitric oxide, α- and γ-tocopherol, the fatty acid composition, activities of superoxide dismutase, catalase, total and Se-dependent glutathione peroxidases, and the antioxidant paraoxonase (PON) family. Results showed that TAA (1.70 ± 0.03 mM versus 1.86 ± 0.03 mM, p < 0.05), α-tocopherol (4.37 ± 0.26 μM versus 5.74 ± 0.30 μM, p < 0.05), PON1 paraoxonase (245 ± 24 nmol/min/ml versus 272 ± 27 nmol/min/ml, p < 0.05), PON1 arylesterase (87.2 ± 4.6 μmol/min/ml versus 99.3 ± 4.8 μmol/min/ml, p < 0.05), and PON3 simvastatinase (13.48 ± 0.52 nmol/min/ml versus 16.29 ± 0.72 nmol/min/ml, p < 0.001) were significantly lower in COH versus NC. Fatty acids from COH were more saturated, increasing palmitate and decreasing the n-6 and total polyunsaturated fatty acids (PUFAs). Docosahexaenoic acid also increased (p < 0.05). Results suggest that COH could lead to premature ovarian aging and provide new insights into the possible prevention of the adverse effects of ovarian hyperstimulation by directing therapeutic applications to the maintenance of the redox balance and fatty acid status, with special attention to paraoxonase proteins and docosahexaenoic acid.