Serum Paraoxonase Activity Research Articles

Assessment of Neutrophil-to-Lymphocyte Ratio, Platelet-toLymphocyte Ratio,Oxidative Stress and Anti Oxidants levels in Polycystic Ovary Syndrome Patients with Low-Grade Chronic Inflammation

Background: The ratio of neutrophils to lymphocytes (NLR) and the ratio of platelets to lymphocytes(PLR)are prognostic factors in many diseases such as inflammatory diseases, cardiovascular diseases andcancer. However, racing NLR and PLR are important, it is important to establish reference values for NLRand PLR in polycystic ovary syndrome (PCOS) patients with mild chronic inflammation.Objective: To determine the neutrophil-lymphocyte ratio (NLR)and platelet-lymphocyte ratio (PLR), andthe relationship between oxidative stress markers and anti oxidants markers in PCOS patients with lowgrade chronic Inflammation. Methodology. The study included 92 patients with PCOS and 46 control. SerumPON1, XO, SOD activities, 8-OHdG and NO levels were measured using enzyme linked immunosorbentassay (ELISA) kits.Results: Concentration of TNF-?, IL-6, IL-8, IL-10 and CRP were significantly higher in PCOS patientscompared with control (P<0.001). Significant increases were recorded in WBC, ANC, PLT, NLR, PLR,and ESR values. A significant decrease in ALC and MPV values in PCOS patients compared with control(P<0.01). Serum XO, SOD activities and NOlevels were higher in PCOS patients than in the control(p<0.001). Serum 8-OHdG levels and PON1 activities were lower in PCOS patients than in the control(p<0.001). Serum CRP values is positively correlated with XO, NO, 8-OHdG and PON1 activity (r=0.377,p<0.008; r=0.560, p<0.007; r=0.387, p<0.006; r=0.481, p<0.009), respectively. Serum CRP values isnegatively correlated with SOD activity in PCOS patients (r=?0.444, p<0.004).Serum XO activities werenegatively correlated with serum PON1 and SOD. Serum XO activities were Positively correlated withserum NO and 8-OHdG levels.Conclusion: Inflammation stimulates the oxidation process and reduces the ability of cellular antioxidantsin PCOS patients. NLR and PLR are good markers of inflammation, their highest values indicate theseverity of the disease and an imbalance between neutrophils and lymphocytes can be linked to cancer andits development.

Evaluation of the relationship between serum paraoxonase-1 activity and superovulation response/embryo yield in Holstein cows.

In this study, the effect of serum paraoxonase-1 (PON-1) activity on superovulation response and embryo yield was evaluated. The study material comprised 50 Holstein cows aged 3–4 years on postpartum day 90–120 with a body condition score of 3–3.25. A progesterone-based estrus synchronization protocol was initially administered to the selected donors. For this purpose, progesterone source was inserted intravaginally (day 0) and gonadotropin-releasing hormone injection was performed (day 6). Seven days after the insertion of progesterone device, follicle-stimulating hormone injections (total dose of 500 µg in decreasing doses for 4 days) were administered for superovulation. On the morning of the ninth day, prostaglandin (PG) F2α was administered, and the progesterone device was removed from the vagina in the evening on the same day. Two days after PGF2α administration, fixed-time artificial insemination was performed in the morning and in the evening. On the day of artificial insemination, blood samples were taken from the donors to determine the serum PON-1 activity. Uterine flushing was performed seven days after insemination. The results revealed that the serum PON-1 activity (mean ± SD, 562.71 ± 140.23 U/l) of the cows that responded to superovulation (donors with total corpus luteum count of ≥3 in both ovaries) was higher than those (389.91 ± 80.51 U/l) that did not (P<0.05). On the day of insemination, a positive correlation was determined between serum PON-1 activity and the counts of total corpus luteum (r=0.398), total oocyte/embryo (r=0.468), transferable embryo (r=0.453), and Code I embryos (r=0.315, P<0.05). Unlike the Code I embryos, there was no significant correlation between serum PON-1 activity and the number of Code III embryos. Moreover, no significant difference in the number of Code III embryos between the two PON-1 groups was observed. However, embryo yield and quality were found to have increased with increased PON-1 activity. Therefore, it was concluded that serum PON-1 activity may be associated with superovulation response, embryo yield and quality in donor cows.

The Antioxidant Enzyme PON1: A Potential Prognostic Predictor of Acute Ischemic Stroke.

Objective Paraoxonase 1 (PON1) is an antioxidant enzyme, which has been proved to be involved in the pathophysiological process of oxidative stress and various neurological diseases in recent years. Although reduced PON1 activity has been reported in patients with acute ischemic stroke (AIS), the prognostic value of PON1 in AIS has not been clearly established. The purpose of this study was to determine whether the baseline serum PON1 activity level is related to the functional outcome of AIS patients. Methods From July 2017 to June 2020, AIS patients within 3 days of symptom onset were continuously prospectively included in the study. On admission, clinical and laboratory data were recorded, and serum PON1 activity was tested. The National Institute of Health Stroke Scale (NIHSS) score was used to evaluate the initial neurologic deficit at admission, and the modified Rankin scale (mRS) was used to evaluate the functional outcome at 3 months. A multiple logistic regression model was used to analyze the relationship between the baseline PON1 activity level and the prognosis of AIS. Results A total of 336 AIS patients were finally included in this study. The serum PON1 activity of AIS patients with good outcomes was significantly higher than that of patients with poor outcomes (193.4 ± 16.3 U/mL vs. 127.2 ± 14.9 U/mL, p < 0.001). However, the comparison of other clinical and laboratory data between AIS patients with good and poor outcomes was not significant (p > 0.05). There was a significant decrease in the mRS score in patients with AIS across serum PON1 quartiles (3.0 ± 1.6, 2.6 ± 1.5, 2.4 ± 1.4, and 2.4 ± 1.3, p = 0.007). Multivariate logistic regression analysis showed that the 3-month functional outcome of AIS patients was significantly correlated with the quartile of serum PON1 activity. Conclusions This study suggests that the serum PON1 activity may be an independent predictor of the functional outcome of AIS patients.

Serum Paraoxonase-1 Activity and Paraoxonase Q192 Gene Polymorphism in a Young, Healthy Population

Serum Paraoxonase-1 Activity and Paraoxonase Q192 Gene Polymorphism in a Young, Healthy Population

Serum paraoxonase-1 levels as an indicator of oxidative stress in patients with vitiligo

ObjectiveTo evaluate the use of serum paraoxonase-1 (PON1) activity as an indicator of oxidative stress in patients with active generalized vitiligo.BackgroundVitiligo is an acquired cutaneous disorder of pigmentation, characterized by destruction of melanocytes. One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. In patients with vitiligo, lower levels of PON1 prevent lipoprotein peroxidation and oxidation of low-density lipoprotein and cholesterol.Patients and methodsA case–control study was conducted on 40 patients: 20 patients with recent active generalized vitiligo and 20 age-matched and sex-matched healthy volunteers served as controls. All the included patients underwent full history taking, full examination, routine laboratory investigations, and assessment of serum PON1.ResultsThe serum PON1 level in patient group A (101.64 ± 25.48) was significantly lower than that in the control group B (181.88 ± 95.12) (P < 0.001). There was a significant negative correlation between serum PON1 level and vitiligo area severity index score (r = −0.780, P < 0.001).ConclusionVitiligo is probably mediated through a process of oxidative stress and imbalance of oxidant–antioxidant system. Oxidative stress present in vitiligo disease can be determined by measurement of serum PON1 in these patients.

The association between serum cortisol, thyroid profile, paraoxonase activity, arylesterase activity and anthropometric parameters of undergraduate students under examination stress

Stress caused due to examinations during any degree program and at any educational level has been observed at all levels so the present study was conducted to investigate the stress related to final examination in undergraduate students with reference to their academic performance. Fifty-four volunteers were divided into three groups, ( n = 18), according to their academic performance, that is, Group A with low CGPA (⩽2.99), Group B with average CGPA (⩾3.00–3.59) and Group C with high CGPA (⩾3.60) and blood samples (3 ml) were taken at three-time intervals, that is, pre-examination, during examination and post examination time interval, at the Department of Physiology, Government College University, Faisalabad. Anthropometric parameters like height, weight, blood pressure, heart rate and body mass index (BMI) were also determined. Blood cortisol and thyroid hormones (triiodothyronine, T3; thyroxine, T4) and thyroid stimulating hormone (TSH)) were measured using ELISA based technique. Arylesterase activity (ARE) and paraoxonase activity (PON-1) were also measured using colorimetric method. The results showed that overall cortisol level was increased at pre-examination and during examination time intervals as compared to the post examination time interval while PON-1 and ARE were significantly ( p &lt; 0.05) decreased. With regards to T4 and TSH, a non-significant ( p &lt; 0.05) difference was observed in pre and post examination time interval. It could be concluded from the current study that semester system examinations significantly ( p &lt; 0.05) imposed stress in all students group at pre-examination interval as compare to post examination interval and this examination related stress was find more in the students already obtained low CGPA as compared to the other studied groups. Although, a correlation between academic performance and examinations stress in semester system was found but a large scale trial in multiple institutions throughout the Pakistan is required to exclude any socioeconomic factors because Pakistan belongs to developing country.

Desmodium gyrans dc modulates lipid trafficking in cultured macrophages and improves functional high-density lipoprotein in male wistar rats.

OBJECTIVE:High-density lipoprotein (HDL) cholesterol-mediated atherosclerotic plaque regression has gained wide therapeutic attention. The whole plant methanolic extract of the medicinal plant Desmodium gyrans Methanolic Extract (DGM) has shown to mitigate hyperlipidemia in high fat- and-cholesterol fed rats and rabbits with significant HDL enhancing property. The study aimed to assess the functionality and mechanistic basis of HDL promoting effect of DGM.MATERIALS AND METHODS:Macrophage cholesterol efflux and foam cell formation assays were performed in THP-1 macrophages. Male Wistar rats were given DGM extract over 1 month and assessed the serum HDL, Apolipoprotein A1 (Apo-A1), and paraoxonase activity. Quantitative Polymerase chain reaction was carried out to assess the expression level of Apo-A1, SR-B1 (Scavenger receptor B1), and Cholesteryl ester transfer protein (CETP) on cDNA of HepG2 cells exposed to DGM.RESULTS:Pretreatment of DGM inhibited uptake of oxidized lipids and enhanced the lipid efflux by THP-1-derived macrophages. Oral administration of DGM (100 and 250 mg/kg) progressively enhanced the serum HDL, Apo-A1 level, and associated paraoxonase activity in normal male Wistar rats. In support to this, DGM exposed HepG2 cells documented dose-dependent increase in the expression of SR-B1 and Apo-A1 mRNA, while reduced the CETP expression.CONCLUSION:Overall the results indicated that DGM modulates lipid trafficking and possesses functional HDL enhancing potential through increased Apo-A1 levels and paraoxonase activity. Further, reduced CETP expression and increased expression of SR-B1 suggest the reverse cholesterol transport promoting role of DGM.

Moringa (Moringa oleifera) leaves aqueous extract enhances fibronectin type III domain-containing protein 5 gene expression and serum irisin liberation in an obesity model

Background Obesity, a risk agent for many chronic diseases, leads to increased mortality and poses one of the major public health problems. Objective This study aimed to investigate the thermogenic and antiobese efficiency of Moringa aqueous extract (MAE) on obese-modeled rats. Materials and methods Adult male rats (150–170 g) were randomly divided into four groups, with 10 animals each, as follows: (a) healthy rats served as control, (b) healthy rats administrated with MAE (400 mg/kg/day), (c) obese-modeled rats, and (d) obese-modeled rats treated with MAE. Results After 30 consecutive days of treatment, the obtained results declared that MAE possessed antiobesity, thermogenic, antilipidemic, and antiinflammatory potential. MAE succeeded significantly in reduction of the BMI and serum leptin level coupled with up-regulation of fibronectin type III domain-containing protein 5 gene mRNA expression and serum irisin level. It clearly increased serum paraoxonase-1 activity and improved lipid profile values. Moreover, it markedly reduced serum tumor necrosis factor α and increased antioxidant activity, which was achieved from the marked improvement in malondialdehyde, nitric oxide, catalase, superoxide dismutase, and glutathione values in cardio-hepatic tissues. These findings were confirmed by the regeneration of the hepatic histopathological structure. Conclusion MAE, as a food supplement, could play a beneficial role in management of obesity and restoring its complications. This could be exhibited through multiple pathways, mainly via upregulation of fibronectin type III domain-containing protein 5 gene expression and production of the soluble myokine ‘irisin,’ which is responsible for browning of white adipose tissue as well as increment of total body energy expenditure.

In vivo/in silico insight into the effect of titanium dioxide nanoparticle on serum paraoxonase 1 activity in rat

Serum paraoxonase1 (PON1) has special function in human body organism including the antioxidant and anti-atherogenic properties. In the present study, the effect of TiO2 nanoparticles on the activity and structure of the PON1 has been evaluated through in vivo and in silico methods. After treatments of the rats with different doses of TiO2 NPs, blood samples were collected and serum PON1 activity was measured by phenylacetate and paraoxon as substrate. In addition, the effects of TiO2 NP on enzyme structure were analyzed through Molecular dynamic (MD) simulation via Gromacs software package to obtain RMSD, RMSF, Rg, SASA, and secondary structures values. A significant reduction (p < 0.05) in arylesterase & paraoxonase activities of serum PON1 were monitored in Spectrometric assays when rats were treated with 150 and 200 mg/kg doses of TiO2 NPs. RMSD, RG, RMSF, and SASA values in the presence of TiO2 have been increased while RMSF values of the L1 and L2 loops (gate of the catalytic site) have been reduced. Moreover, Hydrogen bonds and secondary structure values of the enzyme decreased in the presence of TiO2 NP. All of these MD simulation results could indicate the instability of the PON1 structure bounded to TiO2 NP. TiO2 NP could cause a disturbance in the enzyme structure and function of PON1 based on the results. PON1 prevents oxidation of LDL and can delay atherosclerosis progression while in the presence of TiO2 NP these protective effects could be endangered. Communicated by Ramaswamy H. Sarma

Pullu sazan (Cyprinus carpio L) paraoksonaz ve arilesteraz enzim aktivitelerine curcuminin etkisi

In this study, the effect of curcumin on paraoxonase and arylesterase enzyme activities in scaly carp (Cyprinus carpio) were examined. For this purpose, curcumin was added into the feed during 21 days with 10, 20 and 40 mg/kg doses. At the end of this period, serum, liver and kidney samples were taken from the fish and changes in paraoxonase and arylesterase enzyme activities were investigated. The serum and liver paraoxonase and arylesterase enzyme activities of the curcumin treated groups showed significant increases compared to the control group. The increase in kidney paraoxonase and arylesterase enzyme activities was statistically insignificant.

The Study of Serum Asymmetric Dimethylarginine Concentrations in the Different Paraoxonase Phenotypes of Exudative Age-related Macular Degeneration Disease

Background and Aims: Age-related macular degeneration (ARMD) is a degenerative retinal disorder that causes progressive loss of central vision in older adults. The study aimed to determine the effect of asymmetric dimethylarginine (ADMA) as oxidizing metabolite and paraoxonase (PON1) activity within its phenotypes as an antioxidant agent in the development of such multifactorial disease. Materials and methods: Forty-five exudative ARMD (E-ARMD) patients and 45 healthy controls were enrolled for this case-control study. Serum PON1 activity was measured using paraoxon and phenylacetate as substrates. PON1 phenotype was determined using the double-substrate method. The ADMA and oxidized LDL (OX-LDL) levels were determined by enzyme-linked immunosorbent assay method. Blood lipid profile was measured, and nontraditional lipid indexes were calculated. Results: Three phenotypes were determined for PON1 among the participants in the study, including AA, AB, and BB phenotypes with low, moderate, and high activity, respectively. AA phenotype was more frequent among E-ARMD, while AB and BB phenotypes were more common among healthy subjects. The mean ADMA and OX-LDL levels were significantly higher in the patients comparing to the controls (p=0.02 and p=0.01, respectively). No significant differences were found in ADMA and OX-LDL levels between phenotypes in each group and also among similar phenotypes. LDL, cholesterol, and even all comprehensive lipid indexes except (atherogenic index of plasma) were higher in E-ARMD patients compared with the healthy group. Conclusions: It was concluded that high-risk individuals could be identified by evaluating the blood factors involved in oxidative stress, and antioxidant therapies may reduce the incidence and progression of the disease.

The effect of thyroid hormone status on selected antioxidant parameters in patients with Graves' disease and active thyroid-associated orbitopathy.

Oxidative stress has been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO) in patients with Graves' disease (GD). This study assessed the effect of thyroid hormone abnormalities on selected antioxidant parameters in patients with active TAO. The study group consisted of 56 patients with GD and active TAO treated with antithyroid medication. Depending on the thyroid hormone level, they were subdivided into two groups: Group 1 - hyperthyroid patients (n = 34) and Group 2 - euthyroid patients (n = 22). The total oxidant status expressed as the ferric reducing ability of plasma (FRAP) as well as selected enzymatic and nonenzymatic components of the antioxidant system, including the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and paraoxonase 1 (PON-1), as well as the levels of vitamin C, uric acid, and lipid peroxidation products: malondialdehyde (MDA) and conjugated dienes (CD) were assessed in all enrolled participants. The FRAP values in Group 1 were significantly higher than in controls. The FRAP values in Group 2 were lower than in Group 1 and higher than in controls. However, the differences were not significant. In Group 1, the activity of SOD and GPx, as well as serum levels of uric acid, MDA, and CD, were significantly higher than in controls. At the same time, serum PON-1 activity and vitamin C levels were significantly lower in Group 1 than in controls. In Group 2, the SOD activity as well as MDA and CD levels were non-significantly lower than in Group 1 and non-significantly higher than in controls. The activity of GPx in euthyroid patients with TAO was significantly higher than in controls. Hyperthyroidism is a significant contributor to oxidative stress in patients with active TAO, which manifests as upregulated lipid peroxidation and antioxidant system activation. Euthyroid state restoration leads to a relative reduction in activity and levels of most studied antioxidant parameters, which still remain above the normal values. The autoimmune inflammation of the orbital tissue seems to be a thyroid hormone status-independent modifier of oxidative stress.

Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in murine inflammatory arthritis. K/BxN serum transfer (STIA) or collagen antibody transfer (CAIA) was used for arthritis induction in B6 mice homozygous for the PON1 human transgene [PON1Tg], PON1 knock-out mice [PON1KO], and wild type littermate control mice [WT]. Experiments were also performed in K/BxN mice with chronic arthritis, and in RA patients and healthy controls. Arthritis activity in K/BxN mice was associated with a marked dyslipidemia, lower PON1 activity and higher bioactive lipid mediators (BLM), as well as a dysregulated hepatic lipid gene expression profile. Higher serum PON1 activity correlated with lower BLM and lower arthritis activity in both K/BxN mice and RA patients. Overexpression of the human PON1 transgene was associated with reduced inflammatory arthritis, which correlated strongly with higher circulating PON1 activity, upregulation of the hepatic glutathione pathway, and reduction of circulating BLM. These results implicate PON1 as a potential novel therapeutic target for joint disease in RA with potential for vascular benefit, which warrants further investigation.

Serum paraoxonase 1 activity in cats: analytical validation, reference intervals, and correlation with serum amyloid A and alpha-1-acid glycoprotein

Paraoxonase 1 (PON1) is an inflammation marker associated with lipid oxidation and is used as a diagnostic marker in people. There is no information about the suitable substrate and analytic performance in cats, or its biological behavior compared with other inflammation markers. Our aims were to validate a paraoxon-based method to measure PON1 activity in feline serum, to assess stability of PON1 under different storage conditions and the impact of interfering elements, to determine a reference interval (RI) for healthy cats, and to correlate PON1 activity with 2 major acute-phase proteins. Intra- and inter-assay precision, accuracy, and RI were assessed using fresh serum. The same specimens were stored at room temperature, refrigerated, or frozen, and retested at defined intervals. Hemolysis, lipemia, and icterus were simulated to study interferences. PON1 results were compared to serum amyloid A (SAA) and alpha-1-acid glycoprotein (AGP) results. Analytical validation yielded precise and accurate results. PON1 activity is stable for up to 24 h at room temperature and up to 48 h at 4°C. Freezing at -20°C results in an increase after 72 h, with return to baseline values after 1 wk, that again increases after 6 mo. Only hyperlipemia interfered with PON1 activity. The RI based on 71 healthy cats was 58-154 U/L. PON1 activity was negatively correlated with AGP, but not with SAA. Serum PON1 activity can be measured accurately in cats, and it acts as a negative acute-phase protein.

Paraoxonase 1 gene polymorphisms concerning non-insulin-dependent diabetes mellitus nephropathy in hemodialysis patients

AimsData on involvement of paraoxonase 1 gene (PON1) in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy are scarce. We investigated PON1 polymorphisms concerning end-stage NIDDM nephropathy and atherosclerotic complications in NIDDM nephropathy patients treated with hemodialysis (HD). MethodsIn NIDDM nephropathy (n = 402) and non-diabetic (n = 998) HD subjects, we obtained PON1 polymorphisms by HRM analysis (rs662) or predesigned TaqMan SNV Genotyping Assay (rs854560, rs705379). ResultsOnly PON1 rs705379 was associated with end-stage NIDDM nephropathy in the recessive (OR 1.451, 95% CI 1.104–1.906, P = 0.009) and additive (OR 1.398, 95%CI 1.009–1.936, P = 0.046) inheritance modes. NIDDM nephropathy patients bearing the rs854560 T allele were at higher risk for ischemic cerebral stroke (OR 2.087, 95%CI 1.145–3.801, P = 0.016). In non-diabetic patients but not NIDDM nephropathy subjects, atherogenic dyslipidemia corresponded with PON1 rs662 A allele and PON1 rs854560 TT homozygosity. ConclusionsIn HD patients, NIDDM nephropathy correlates with the TT genotype of PON1 rs705379. The rs854560 T allele indicates a higher risk for atherosclerotic diseases in NIDDM nephropathy subjects. The T alleles of both PON1 SNVs are known as low expression variants downregulated serum PON1 activity. An increase of diminished PON1 activity may be a target in the prevention of NIDDM nephropathy and NIDDM atherosclerotic complications.

Paraoxonase Activity and Phenotype Distribution in Patients with Chronic Obstructive Pulmonary Disease.

Paraoxonase 1 (PON1) and arylesterase (ARE) enzymes have an important role in the prevention of oxidative stress which is related to the pathogenesis of chronic obstructive pulmonary disease (COPD). PON1 levels vary widely among individuals and ethnic groups, which is in part associated with polymorphisms. We investigated PON1 and ARE activity and phenotype distribution in COPD patients and healthy individuals. Sixty six COPD patients and 59 control subjects were involved in the study. Serum PON1 and ARE activities were detected by spectrophotometric method. The ratio of salt-induced PON1 to ARE activity was used to determine phenotypes as QQ, QR, and RR. COPD patients exhibited higher PON1 activity (199.1 vs 129.2, p=0.002) but lower ARE activity compared to control (21.3 vs 33.5, p=0.021). There was a significant difference between COPD and control group with respect to PON1 phenotype characteristics. RR phenotypic distribution was more common in the COPD group than in control (60.6% [95% CI: 48.8 - 72.3] versus 22.0 % [95% CI: 12.0 - 31.9], p=0.001). We also found that smoking (95.0% CI: 0.001-0.036, p<0.001) and RR phenotype (95.0% CI: 0.006 - 0.59, p=0.016) are independent determinants in COPD. We found that RR phenotype was more common in COPD patients compared to control. Smoking and RR phenotype may be defined as independent factors associated with COPD.

P1275PARAOXONASE 1 (PON1) GENE POLYMORPHISMS, PON1 EXPRESSION IN PBMCS, AND SERUM PON1 ACTIVITY CONCERNING DYSLIPIDEMIA AND RELATED COMORBIDITIES IN HEMODIALYSIS (HD) PATIENTS

Abstract Background and Aims PON1 may prevent atherosclerosis influencing lipid metabolism and exerting antioxidant and anti-inflammatory activities. We focused on serum PON1 activity in HD patients concerning dyslipidemia, coronary heart disease (CHD), myocardial infarction (MI), and cerebral stroke (CS). PON1 activity was related to PON1 polymorphisms, PON1 expression in PBMCs, and demographic, clinical, and laboratory data. Method In 93 HD patients (men 55, age 66.7, 18.3 – 86.2 years, renal replacement therapy duration 3.9, 0.2 – 22.3 years, CHD 25, MI 15, CS 9), dyslipidemia was diagnosed by K/DOQI guidelines. The TG/HDL-cholesterol ratio of ≥3.8 indicated atherogenic dyslipidemia. Standard diagnostic rules were applied for CHD, MI, and CS recognition. PON1 activity was measured in serum using an automated PON1 assay kit. PON1 polymorphisms were genotyped by high-resolution melting curve analysis (rs662) or using predesigned TaqMan SNV Genotyping Assay (rs854560 and rs705379). In 46 subjects, the relative PON1 transcript level was determined in PBMCs using reverse transcription-quantitative polymerase chain reaction analysis. Results In univariate analyses, the lower serum PON1 activity the higher frequency of mixed dyslipidemia (LDL ≥ 100 mg/dL, TG ≥ 200 mg/dL, non-HDL ≥ 130 mg/dl; β ± SE: -21.4 ± 10.0, P = 0.035) and the higher serum TG levels (β ± SE: -1.06 ± 0.49, P = 0.034). Normalized serum PON1 activity (the PON1/HDL ratio) correlated positively with male sex (β ± SE: 0.56 ± 0.25, P = 0.029), atherogenic dyslipidemia (β ± SE: 0.67 ± 0.25, P = 0.008), and cigarette smoking (β ± SE: 0.86 ± 0.42, P = 0.043). After adjustment for gender, cigarette smoking, urine output, living in rural area, and serum phosphorus, significance was maintained between normalized serum PON1 activity and atherogenic dyslipidemia (β ± SE: 0.54 ± 0.24, P = 0.028), male sex (β ± SE: 0.51 ± 0.24, P = 0.037) and cigarette smoking (β ± SE: 0.93±0.41, P = 0.024) as well as revealed for living in rural area (β ± SE: 0.55 ± 0.26, P = 0.039), urine output (β ± SE: -0.14 ± 0.07, P = 0.046), and zinc supplementation (β ± SE: 1.5 ± 0.67, P = 0.029). PON1 activity (101, 27.7 – 213 U/L) and normalized PON1 activity (2.27, 0.57 – 7.10) were not influenced by PON1 polymorphisms and did not yield differences in patients stratified by CHD, MI, CS, and dyslipidemic patterns except atherogenic dyslipidemia. The latter relationship was caused by a correlation between serum PON1 activity and TG (r = -0.220, P = 0.034). PON1 transcript was detected in PBMCs of 9 subjects. They showed a higher prevalence of the AG + GG genotypes of PON1 rs662 (77.8% vs. 34.3%, P = 0.027), a higher serum CRP level (7.8, 2.8 – 46.8 mg/L vs. 3.9, 0.4 – 23.0 mg/L, P = 0.042), and a lower albumin (3.9, 2.6 – 4.5 g/dL vs. 4.2, 3.2 – 4.6 g/dL, P = 0.025) compared with the results of 37 subjects without the PON1 expression. The relative PON1 transcript level did not correlate with serum PON1 activity (r = 0.042, P = 0.915). Conclusion In HD patients, serum PON1 activity is associated with atherogenic dyslipidemia but not with already developed CHD and history of MI or CS, even after adjustment for several confounding variables. Illegitimate PON1 transcription occurs in uremic PBMCs at very low level and is influenced by PON1 rs662 polymorphism and upregulated by inflammation. PON1 could be considered as a therapeutic target in prevention of atherosclerosis and its complications in uremic patients.

Comparison of Oxidant and Antioxidant Parameters in Patients with Sjögren’s Syndrome and Healthy Subjects

Abstract Objective Oxidative stress may have an effect on the pathogenesis of diseases, including autoimmune rheumatic diseases. We aimed to investigate the serum paraoxonase activity and other oxidant/antioxidant parameters in patients with Sjögren’s syndrome (SS) and healthy controls. Methods 85 patients with SS and 65 healthy subjects were included in the study. Groups were age and gender-matched and had no liver disease. Serum paraoxonase (PON)-1 activity, stimulated paraoxonase (SPON), PON-1 phenotypes that represent polymorphism (Q192R; QQ, QR, RR), arylesterase (ARE), total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), advanced oxidative protein products (AOPP), total thioles (TTL) and ischaemia-modified albumin (IMA) were measured in all study participants. Results Statistically significant differences were found in the QQ and QR+RR phenotype of PON-1 for TAC, TOS and TTL (p&lt;0.001) between SS and healthy groups. The other parameters were statistically insignificant. Conclusion Antioxidant parameters were lower in SS patients compared with healthy controls. Conversely, oxidant parameters were higher. This imbalance may play a role in SS pathogenesis.

Paraoxonase-1 Enzyme Activity and Oxidative Status in Pulmonary Hypertension Original Article

Objective: Oxidative stress has been considered to be one of the main causes for the development of pulmonary hypertension (PH) via leading alteration of pulmonary vasomotor tone induced by hypoxia. The aim of this study is to determine the serum paraoxonase-1 enzyme (PON-1) activity, arylesterase activity, the antioxidant-oxidant status in patients with PH and to compare with healthy controls.&#x0D; Material and Methods: Thirty five healthy ındividuals (mean age 45.7±5.9 years) as a control group and thirty eight patients (mean age 46.5±12.6 years) with a diagnosis of PH wereincluded in thestudy. Serum PON-1 and arylesterase activity, the total antioxidative capacity of plasma (TAC) and total oxidantstatus (TOS) were measured by using colorimetric methods. The Oxidative Stress Index (OSI) wascalculated as TOS/ TACX100.&#x0D; Results: Serum PON1 activity is significantly lower in PH patients when compared with healthy controls (p=0.001). The serum arylesterase activity and TAC, TOS and OSI status were similarin bothgroups. There is inverse correlation between serum PON1 activityand NYHA functionalcapacity (r:-0.649 p=0.001). Furthermore, PON1 activity of study patients are similarin the PH subgroups. Serum activity of PON1 wasfoundto bethe only independent parameter for the presence of PH in binary logistic regression analysis (OR 0.984, 95 % CI 0.977-0.992, p=0.001). Eight patients died follow up period (27.6±14.5 months) and none of theparametersincluding PON1 were associated with mortality.&#x0D; Conclusion: Serum PON1 activity of PH patients is lowerthanhealthypopulation, but does not predictmortality.&#x0D; Bangladesh Journal of Medical Science Vol.19(4) 2020 p.652-658

Cladribine Treatment Improved Homocysteine Metabolism and Increased Total Serum Antioxidant Activity in Secondary Progressive Multiple Sclerosis Patients.

Hyperhomocysteinemia plays a crucial role in the pathogenesis of many diseases of the central nervous system (CNS). The nervous system is particularly sensitive to high homocysteine (Hcy) level mainly due to its prooxidative and cytotoxic effects. Cladribine, a drug recently registered for the treatment of multiple sclerosis (MS), possesses additionally neuroprotective effects which are independent of its peripheral immunosuppressant action. Accumulating evidence suggests that oxidative stress and homocysteine thiolactone-mediated protein homocysteinylation play a causal role in MS. Both of these processes may be attenuated by paraoxonase 1 (PON1). Therefore, in the present study, we aimed to examine whether the beneficial effects of the drug in MS patients with a secondary progressive (SP) clinical course, treated with cladribine subcutaneously (s.c.), may be related to its ability to modify serum PON1 activity, Hcy concentration, and protein homocysteinylation, as well as to correct total antioxidant status. A total of 118 subjects were enrolled into the study: (1) patients with a SP type of MS, SP-MS (n = 40); (2) patients with a relapsing-remitting (RR) type of MS, RR-MS (n = 30); and (3) healthy people (n = 48). Patients with SP-MS were treated with cladribine. The drug was given in SP-SM patients s.c. six times every 6 weeks up to a total mean cumulative dose of 1.8 mg/kg. PON1 activity was assessed spectrophotometrically. The level of Hcy, homocysteine thiolactone (HTL) attached to plasma proteins (N-Hcy-protein), and antibodies against homocysteinylated proteins was assessed with an enzyme immunoassay. The total antioxidant activity of the serum was assessed with the ferric-reducing activity of plasma (FRAP) method. Basically, there was no difference in PON1 activity between untreated SP-MS, RR-MS, and control subjects. Serum Hcy was significantly higher in RR-MS patients (p < 0.001) and in SP-MS patients (p < 0.01) compared to the control group. The N-Hcy protein level was higher in RR-MS patients (p < 0.05) in comparison to the control group. Moreover, the elevated level of antibodies against homocysteinylated proteins was observed in the serum of patients with SP-MS. The total antioxidant capacity of serum was lower in MS patients vs. the control group (p < 0.001). After cladribine treatment, the activity of PON1 did not change in SP-MS patients, whereas cladribine treatment decreased the level of total Hcy (p < 0.05). Treatment with cladribine increased the total serum antioxidant activity in SP-MS patients (p < 0.01). The Expanded Disability Status Scale (EDSS) score did not change in SP-MS patients. Cladribine treatment in the SP-MS group attenuates hyperhomocysteinemia-induced protein homocysteinylation (n.s.). It also stabilises the neurological condition of SP-MS patients. The stabilisation of a neurological condition observed in SP-MS patients after cladribine treatment may be partially related to its ability to reduce elevated Hcy level and to improve serum antioxidant potential.