Serum Paraoxonase Activity Research Articles

Study of Oxidative Stress Marker Serum Paraoxonase in Metabolic Syndrome

Purpose: The metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin that appear to promote development of cardiovascular disease. It has become one of the most important topics for this decade because of marked increase in cardiovascular disease associated with risk factors. Paraoxonase (PON) is a family of three enzymes, PON1, PON2 and PON3, the gene which is located on chromosome 7. This is high-density lipoprotein (HDL)-associated enzyme with antioxidant activity. The objective of the present study aimed at measurement of PON1 activities in patients with MetS, to compare PON1 activities in patients with MetS with those in controls and assess its relationship with the lipoproteins in serum. Material and Method: Cases were included as per the criteria put forth by the International Diabetes Federation. Serum PON1 activities were measured using spectrophotometer. Statistical analysis was done using SPSS 20.0. Result: Serum PON1 arylesterase and lactonase activities were found to be reduced significantly in patients with MetS than in controls. PON1 activities showed a positive correlation with HDL, fasting blood glucose and diastolic blood pressure. Linear regression analysis showed a significant correlation between PON1 activities and body mass index. Discussion: From the present study, it is clear that reduction in PON1 activities in MetS is mainly due either to abnormalities with synthesis or secretion of HDL cholesterol or oxidative stress as a consequence of excess production of the free radicals. This study also iterates that it is the quality and not the quantity of HDL cholesterol is important while studying the pathophysiology of MetS.

Serum Paraoxonase activity in relation to lipid profile in Age-related Macular Degeneration patients

Age-related Macular Degeneration (AMD) is a multifactorial disease causing visual impairment in old age. Oxidative stress is one of the main contributors for the disease progression. Paraoxonase (PON), a HDL-resident antioxidant enzyme which removes oxidized low density lipoprotein (oxLDL), which is not studied much in AMD. This study assesses the PON activities in relation to the lipid status and genetic variants in AMD patients. In this prospective case-control study, a total of 48 AMD patients and 30 unrelated healthy controls were recruited. The serum oxLDL and Plasma Homocysteine (Hcy) levels were estimated by ELISA. Plasma Homocysteine thiolactone (HCTL) was estimated by HPLC. Serum PON activities were estimated by spectrophotometry. PON gene expression was assessed by qPCR and protein expression by western blot, immunofluorescence and FACS analysis. Two known single nucleotide polymorphisms (SNPs) in the coding region of PON1, Q192R and L55M variants were checked in the AMD patients and controls and their association with PON activity and lipid levels were determined. Serum paraoxonase (PONase) and thiolactonase (PON-HCTLase) activities were significantly elevated in AMD patients than in controls apart from elevated serum levels of total cholesterol (TC), triglycerides (TG), oxLDL. While serum LDL levels in AMD patients correlate positively with PON HCTLase activity, the serum high density lipoprotein (HDL) correlates with both PONase and PON-HCTLase activities. However, multiple regression analysis showed that, amongst the parameters, only serum TG was a significant risk factor for AMD, after adjusting for demographic parameters as well as cataract. PON2 was significantly increased at the level of gene expression (p = 0.03) as seen in circulating peripheral blood mononuclear cells (PBMC) of AMD patients possibly mediated by the transcription factor SP1, that showed 2-fold increase. PON1 and 2 protein expressions also showed significant increase in the PBMC of AMD patients. At serum level, PON1 protein was significantly increased in AMD patients. Cholesterol transporters such as CD36, SR-B1 and ABCA1 gene expressions were also found to be higher (1.5, 1.9 and 2.4-fold respectively) in AMD, though not statistically significant. While the wet AMD (CNV) was found to be associated with increase in oxLDL and serum PONase activity, the dry AMD was associated with increased HDL and serum PON-HCTLase activity. The genotype and allele frequencies of Q192R & L55M were not significantly different between AMD patients and controls. However, altered lipid status and PON activities were associated with the genotype in AMD patients. A higher enzyme activity was observed for the RR genotype of Q192R in the cohort, irrespective of case and control. Thus the PON genotype and phenotype seem to play a role in the pathogenesis of AMD.

Antibodies to paraoxonase 1 are associated with oxidant status and endothelial activation in rheumatoid arthritis.

Traditional and non-traditional cardiovascular (CV) risk factors underlie CV disease occurrence in rheumatoid arthritis (RA). Recently, a functional impairment of high-density lipoprotein (HDL) has been observed. Although the actual players are unknown, anti-HDLs were associated with altered lipid profile, decreased paraoxonase 1 (PON1) activity and CV disease in RA. Therefore, we aimed to evaluate whether the presence of antibodies against PON1 may be involved in this scenario. IgG anti-PON1 antibodies were quantified by ELISA in serum samples from 212 RA patients, 175 healthy controls (HC) and 54 subjects with traditional CV risk factors (CVR). A subgroup of 13 RA patients was prospectively followed upon tumour necrosis factor-α (TNFα) blockade. Serum PON1 activity, nitric oxide (NO) and total antioxidant capacity (TAC) were measured. Interferon-γ (IFNγ), interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule (sICAM) and TNFα serum levels were assessed by immunoassays. PON1 rs662 (Q > R) status was studied by reverse transcription (RT)-PCR. IgG anti-PON1 antibodies are increased in RA patients compared with HC (P<0.0001) and CVR subjects (P<0.001), even after correcting for total IgG levels. Although no associations with lipid profile were found, a positive correlation with Health Assessment Questionnaire (HAQ) was observed (r=0.215, P=0.004). Anti-PON1 antibodies were associated with PON1 activity, NO and TAC, a rs662-mediated gene-dosage effect being found. Similarly, anti-PON1 antibodies were associated with sICAM serum levels in univariate and multivariate models. Finally, these antibodies were not affected by TNFα blockade. Anti-PON1 antibodies can be responsible for PON1 impairment in RA patients, with a potential impact on biomarkers of oxidative status and endothelial activation. A gene-environment interaction of rs662 variants is supported.

Relationship between MPV and paraoxonase-1 activity, brachial artery diameter and IMT in patients with diabetes mellitus

Aims: Higher mean platelet volume (MPV) in diabetic patients has been considered as an emerging risk factor for diabetes related micro- and macrovascular complications. Human paraoxonase 1/arylesterase (PON1), which has antioxidant and antiatherogenic properties, is documented in high oxidative stress conditions like uncontrolled diabetes. The present study aimed to evaluate the relationship between mean platelet volume (MPV) and paraoxonase-1 (PON-1) activity, brachial artery diameter (BAd) and intima media thickness (BA-IMT), in diabetic patients with regard to obesity and diabetic complications.Methods: Two-hundred and one diabetic patients (mean age: 52.4 ± 13.4 years, 73.6% females) were grouped according to obesity and diabetic complications (microvascular and macrovascular). Data on demographics, anthropometrics, diabetic complications, MPV levels, BAd and BA-IMT, and serum paraoxonase and arylesterase activities were recorded. The correlation of MPV values to paraoxonase and arylesterase activities, BAd and BA-IMT was evaluated.Results: Paraoxonase and arylesterase values were 119.8 ± 37.5 U/L and 149.0 ± 39.9 U/L, respectively, with no significant difference in respect of obesity and macrovascular complications. Significantly lower values for paraoxonase (107.5 ± 30.7 vs. 123.9 ± 38.8 U/L, p = 0.007) and arylesterase (132.1 ± 30.2 vs. 154.7 ± 41.2, U/L, p = 0.001) were noted in patients with microvascular complications. MPV values were 9.10 ± 0.87 fL, with no significant difference across the groups and no significant correlation with other parameters.Conclusion: In conclusion, PON-1 activity is more significantly decreased in diabetic patients with microvascular than macrovascular complications with no effects on MPV values. On the other hand, no relationship was found between thrombogenic activity and PON-1 activity, BAd and BA-IMT regardless of obesity and diabetic complications.

Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p < 0.001), whereas MDA levels were significantly higher ( p < 0.001). No significant correlation was found between serum paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.

The relationship between serum paraoxonase levels and carotid atherosclerotic plaque formation in Alzheimer's patients

Low paraoxonase 1 (PON1) activity and carotid atherosclerosis have been suggested to be important risk factors for dementia. However, the studies to date could not fully clarify the relationship between PON1, carotid atherosclerosis and dementia. The present study aimed to measure carotid atherosclerosis and PON1 activity in Alzheimer's Disease and to evaluate the relationship between them. The study included 25 Alzheimer's patients and 25 control subjects, for a total of 50 individuals. The study measured the serum PON1 activity and other biochemical parameters and carotid atherosclerotic plaque values of the participants. The mean paraoxonase activity (31.06±2.31U/L) was significantly lower in the Alzheimer's group compared to the control group (59.05±7.05U/L) (P<0.001). Nonetheless, the carotid plaque values were significantly higher in the patient group (3.02±0.52mm) compared to the control group (1.84±0.45mm) (P<0.001). Furthermore, there was a negative correlation (81.0%) between PON1 activity and carotid plaque in the overall study group (P<0.05). Also serum homocystein level was higher in the patient group (22.15±7.05) compared to the control group (13.30±3.32). In conclusion, our findings show inverse association between PON1 activity and carotid atherosclerosis in Alzheimer patients: the lower the PON1 activity the more progressed the atherosclerotic process in AD.

Strenuous physical exercise accelerates the lipid peroxide clearing transport by HDL.

Physical exercise has cardioprotective functions, which have been partly linked to high-density lipoprotein (HDL), and its functions. We studied the effects of endogenous oxidative stress, induced by acute exhaustive physical exercise, on concentration of oxidized HDL lipids. Twenty-four male national top-level endurance runners, 12 middle-distance runners and 12 marathon runners performed a maximal run on a treadmill until exhaustion. We analyzed concentrations of oxidized HDL (oxHDLlipids) and LDL lipids (oxLDLlipids), serum antioxidant potential (TRAP), paraoxonase activity and malondialdehyde. Venous blood samples were taken before, immediately, 15 and 90min after exercise. Immediately after the treadmill run the concentration of oxHDLlipids was increased by 24% (p<0.01). Simultaneously, the ratio of oxHDLlipids to oxLDLlipids increased by 55% and the oxLDLlipids levels decreased by 19% (p<0.001), while serum malondialdehyde and TRAP increased by 54% (p<0.001) and 29% (p<0.01), respectively. After the 90min recovery the concentration of oxHDLlipids was decreased towards the pre-exercise level, but that of oxLDLlipids remained decreased below pre-exercise values (p<0.001). The change in oxLDLlipids after the run correlated positively with VO2max (r=0.67, p<0.001) and negatively with the change in paraoxonase activity (r=-0.47, p<0.05). We conclude that acute exhaustive physical exercise increased the concentration of oxHDLlipids and decreased that of oxLDLlipids and the ratio of oxLDLlipids to oxHDLlipids, which suggests that during physical exercise HDL has an active role in the removal of lipid peroxides.

L'extrait aqueux lyophilisé de Portulaca oleracea prévient contre la peroxydation lipidique en augmentant l'activité de la paraoxonase-1 sérique, chez des rats soumis à un régime enrichi en cholestérol

L'extrait aqueux lyophilisé de Portulaca oleracea prévient contre la peroxydation lipidique en augmentant l'activité de la paraoxonase-1 sérique, chez des rats soumis à un régime enrichi en cholestérol

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria.

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

Decreased arylesterase activity of paraoxonase-1 (PON-1) might be a common denominator of neuroinflammatory and neurodegenerative diseases

High-density lipoprotein (HDL)-bound paraoxonase-1 (PON-1) is mechanistically related to oxidative stress, inflammation and atherosclerosis and this multirole nature positions the enzyme as potential pathogenic player and candidate biomarker for many diseases. Our previous work suggests that decline in serum PON-1 activities, i.e. arylesterase and paraoxonase, might be associated with the occurrence of mild cognitive impairment (MCI) to late onset Alzheimer’s disease (LOAD) or vascular dementia (VAD). The present study aimed to: (1) expand our previous findings in a larger and different population, including patients with LOAD-VAD mixed dementia (MD); (2) explore a possible association between PON-1 and multiple sclerosis (MS); (3) evaluate if cerebrospinal fluid (CSF) levels of PON-1 activities might be useful biomarkers for MS. We found that serum arylesterase, but not paraoxonase, levels of PON-1 were significantly lower in patients affected by MCI (n=232), VAD (n=65), LOAD (n=175), MD (n=88) as well as those with MS (n=104) as compared to healthy controls. Notably, the most pronounced decline in this activity was shown by MD (−18%, p<0.01) and MS (−23%, p<0.001), while the lowest changes were detected in the MCI group (11%, p<0.05). Only arylesterase was detectable in the CSF of MS patients and the levels were not significantly different from those detected in the other two neurological control groups. Overall our data suggest that a depressed arylesterase activity could be a common denominator of different neurological diseases which, independently of their peculiar ethiopathogenesis and pathophysiology, appear to be all characterized by an altered systemic redox balance.

Serum anti-Müllerian hormone levels in euthyroid adolescent girls with Hashimoto's thyroiditis: relationship to antioxidant status

ObjectiveFree radical-mediated oxidative stress has been implicated in the etiopathogenesis of Hashimoto's thyroiditis (HT), which is the most common thyroid disorder in adolescents. HT requires lifelong thyroid surveillance, particularly in women of childbearing age to avoid adverse effects on reproductive function. The aims of this study were to investigate serum concentrations of anti-Müllerian hormone (AMH), a marker of ovarian reserve, in euthyroid adolescent girls with newly diagnosed HT and explore the relationships between AMH levels and biomarkers of antioxidant status. Study designWe recruited 57 non-obese (body mass index [BMI] Z-score<2) adolescent girls with newly diagnosed HT and 50 age- and BMI-matched healthy controls for this case–control study. All participants were euthyroid. Hormonal and metabolic parameters, serum levels of AMH, and antioxidant status [paraoxonase (PON) and arylesterase (ARE) activities] were assessed. ResultsSerum AMH levels were significantly higher and serum PON and ARE activities were significantly lower in adolescents with HT than in the controls (p<0.001 for all). No significant associations were detected between the AMH level and any of the clinical or biochemical parameters in the control group. Serum AMH levels were negatively correlated with PON (r=−0.435, p=0.001) and ARE (r=−0.422, p=0.001) activities in adolescents with HT. ConclusionThe AMH level was significantly higher while the PON and ARE activities were significantly lower in euthyroid adolescent girls with newly diagnosed HT.

Paraoxonase 1 Activity Is Modulated by the rs662 Polymorphism and IgG Anti-High-Density Lipoprotein Antibodies in Patients With Rheumatoid Arthritis: Potential Implications for Cardiovascular Disease.

Paraoxonase 1 (PON-1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme that plays an important role in HDL-mediated cardioprotection. Although genetic polymorphisms are known to modulate PON-1 activity, its involvement in cardiovascular disease (CVD) in rheumatoid arthritis (RA) is controversial, suggesting that other factors may modulate its function. Since anti-HDL antibodies have been found to be related to an impaired lipid profile and occurrence of CVD in RA, this study was undertaken to examine the associations between PON-1 activity, anti-HDL antibodies, and CVD according to PON1 genetic variants in patients with RA. Serum PON-1 activity, using paraoxon as substrate, and IgG anti-HDL antibodies were quantified in 212 RA patients and 110 healthy controls. The PON1 rs662 genotype (Q>R) was determined with TaqMan probes. An additional group of 13 biologics-naive patients with RA was prospectively followed up for 3 months. PON-1 activity was decreased in RA patients compared to healthy controls (P = 0.005), and an effect of the rs662 genotype was noted in both groups, with Q/Q homozygotes exhibiting the lowest PON-1 activity. The distribution of rs662 genotypes did not differ between RA patients and healthy controls (P = 0.215). In patients carrying the Q/Q genotype, anti-HDL antibodies were associated with impaired PON-1 activity (P = 0.010), and levels of anti-HDL antibodies were associated with decreased HDL levels (r = -0.680, P < 0.001) and higher prevalence of cardiovascular events, as determined in univariate and multivariate models. Furthermore, change in anti-HDL antibody levels upon tumor necrosis factor blockade was an independent predictor of improved PON-1 activity (β = -0.369, 95% confidence interval -0.669, -0.069; P = 0.024). PON-1 activity is impaired in RA in association with the rs662 genotype and anti-HDL antibodies, the latter being recognized as a pivotal player in the link between rs662 and CVD in patients with RA.

Relation of mean platelet volume with serum paraoxonase-1 activity and brachial artery diameter and intima media thickness in diabetic patients with respect to obesity and diabetic complications

Relation of mean platelet volume with serum paraoxonase-1 activity and brachial artery diameter and intima media thickness in diabetic patients with respect to obesity and diabetic complications

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia.

Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

Comparison of serum paraoxonase and arylesterase activities between iron deficiency anemia patients and chronic kidney disease patients with anemia

Objective: Altered paraoxonase (PON) and arylesterase (ARE) activities have been shown in anemic chronic kidney disease (CKD) patients and in iron deficiency anemia (IDA) patients. Whether accompanying anemia alone is responsible for this diminished PON and ARE activities in CKD patients or an additive factor for this is not well studied. Therefore, we tried to clarify this issue here. Methods: A total of 82 subjects that consisted of 19 patients with IDA (group 1), 23 anemic CKD patients (group 2), and 40 age and sex matched healthy subjects (group 3) were enrolled. Carotid intima media thickness (CIMT), serum total thiol (–SH), PON, and ARE activities of the participants were analyzed. Results: Group 2 patients had significantly lowest serum levels of Total –SH, PON and ARE. Further comparison showed that total –SH, PON and ARE levels were lower in group 1 than group 3 (p = 0.0001 in both). Regarding comparison of group 1 and 2, only serum ARE levels were significantly lower in group 2 (p = 0.001). PON activity was not different between group 1 and group 2 whereas ARE activity was lower in group 2 than groups 1 and 3. In addition, correlation analysis showed that CIMT was negatively correlated with PON and ARE. Conclusions: This markedly decreased ARE activity in CKD patients, which could not be explained by the anemia alone, may have a role in the pathogenesis of increased atherosclerosis in such patients. Still further studies are needed to certain this.

In vivo effects of curcumin on the paraoxonase, carbonic anhydrase, glucose-6-phosphate dehydrogenase and β-glucosidase enzyme activities in dextran sulphate sodium-induced ulcerative colitis mice

Increases in the risk of infections and malignancy due to immune suppressive therapies of inflammatory bowel diseases (IBDs) have led the researchers to focus on more nontoxic and acceptable natural products like curcumin. Here we investigate whether prophylactic and therapeutic application of the curcumin alters the enzyme activities of paraoxonase (PON), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and cytosolic β-glucosidase in dextran sulphate sodium (DSS)-induced ulcerative colitis mice. Prophylactic application of curcumin resulted in higher MPO activity, less body weight loss and longer colon lengths compared to therapeutic group indicating preventive role of curcumin in IBDs. DSS-induced decrease in liver and serum PON activities were completely recovered by prophylactic administration of curcumin. DSS-induced reduction in liver cytosolic β-glucosidase activity was not affected by curcumin neither in the prophylactic group nor in the therapeutic group. Erythrocyte CA activity was significantly increased in curcumin groups, however no remarkable change in G6PD activity was observed.

Serum 8-isoprostane levels and paraoxonase 1 activity in patients with stage I multiple myeloma

Objective: Multiple myeloma (MM) is a plasma cell malignancy comprising 15% of hematological malignancies. Many studies have assessed the relationship between free radicals and tumor progression or cancer risk. We aimed to evaluate the antioxidant activity of paraoxonase 1 (PON1), arylesterase (ARE), and 8-isoprostane in patients with stage I MM.Materials and methods: Spectrophotometric assays of serum PON1 and ARE activities in addition to serum 8-isoprostane level were performed in 34 patients newly diagnosed with stage I MM as compared to 35 age- and sex-matched individuals who comprised the healthy control group.Results: A significant reduction was found in the activities of PON1 and ARE (for both, P < 0.001) in the patient group. The ratio of PON1/high-density lipoprotein was significantly lower in the MM patient group than in the control group (P < 0.001), while 8-isoprostane levels compared with the control group were significantly higher (P < 0.001), observations that may indicate an increase in oxidative stress in stage I MM patients.Conclusion: A decrease in PON1 activity and increase in 8-isoprostane serum activities in patients may indicate the importance of lipid peroxidation in MM disease. Oxidative stress and especially lipid peroxidation could reduce the antioxidant activity of PON1 and ARE in MM patients and could be considered as factors in the pathogenesis of MM disease.

Vitamin E Improves Serum Paraoxonase-1 Activity and Some Metabolic Factors in Patients with Type 2 Diabetes: No Effects on Nitrite/Nitrate Levels

Objective: It is known that markers of oxidative stress and nitrite/nitrate anion (NOx) increase and activity of antioxidative enzyme paraoxonase-1 decline in type 2 diabetes mellitus (DM). The effects of vitamin E on paraoxonase-1 activity and NOx in patients with type 2 diabetes are not known. The purpose of this study was to examine the hypothesis that vitamin E supplementation would affect paraoxonase-1 activity, metabolic factors, and NOx in patients with DM. Methods: This double-blind, randomized, controlled clinical trial was conducted on 83 patients with DM aged 30–60 years. Forty-two of the subjects had taken 400 IU/day vitamin E and 41 were given placebo over 8 weeks. Fasting blood samples, anthropometric measurements, and dietary intake data were collected at the baseline and at the end of the trial. Results: Vitamin E significantly increased serum vitamin E level, paraoxonase-1 activity, and total antioxidant status (TAS) and decreased fasting blood sugar (FBS) compared to the control group (p < 0.05). Hemoglobin A1c, serum insulin, and insulin resistance significantly decreased in the vitamin E group compared to baseline values (p < 0.05). Alterations in serum levels of malondialdehyde and NOx were not significant in any of groups (p > 0.05). Conclusions: Vitamin E improved serum vitamin E level, paraoxonase-1 activity, TAS, and FBS in patients with type 2 diabetes. Longitudinal studies are warranted to assess the outcome of these results in reducing complications of diabetes in patients with type 2 diabetes.

Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats.

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

Paraoxonase and arylesterase levels in autoimmune thyroid diseases

Objective: The aim of this study was to evaluate serum paraoxonase-1 (PON1) activity and its association with oxidative stress in autoimmune thyroid disease (AITD).Methods: A total of 50 patients with AITD, including 25 with Hashimoto's thyroiditis and 25 with Graves’ disease were enrolled. The control group comprised 27 healthy subjects. Blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment. Serum samples from patients with AITD and the healthy control group were analyzed for basal PON1, salt-stimulated PON1, and arylesterase (ARE) activities, along with lipid hydroperoxide (LOOH) and total free sulfhydryl (–SH) levels.Results: Serum PON1 activities and –SH levels were significantly lower (P < 0.001, for each), whereas LOOH levels were significantly higher (P < 0.001, for each) in patients with AITD, compared to the control group. We observed no significant differences in ARE levels between the patient and healthy control groups (P > 0.05). PON1 activity was positively correlated with –SH (r = 0.522, P < 0.001) and negatively correlated with LOOH (r = −0.487, P < 0.001). PON1 phenotype distribution of the subjects was not significantly different among the three groups (P = 0.961).Conclusions: Serum PON1 activity is decreased in patients with AITD, and correlated positively with –SH, a well-known antioxidant, and negatively with LOOH, an index of lipid oxidation.