PON1 Levels Research Articles

Effect of Inorganic Dietary Selenium Supplementation on Selenoprotein and Lipid Metabolism Gene Expression Patterns in Liver and Loin Muscle of Growing Lambs.

Effect of selenium (Se) supplementation on the selenoprotein and lipid metabolism gene expression patterns in ruminants, especially in lambs is not yet fully understood. The aim of study was to evaluate the effect of Se supplementation on the messenger RNA (mRNA) expression patterns of selected selenoproteins and genes related to lipid metabolism in growing lambs. The experiment was conducted on 48 Polish Merino lambs divided into two groups (n = 24): control (C)—lambs fed with a basal diet (BD) with no Se supplementation, and supplemented (S)—lambs fed with a BD, supplemented with 0.5 mg Se/kg as sodium selenate for 8 weeks. Expression of 12 selenoproteins and six genes related to lipid metabolism was analyzed in the liver and longissimus dorsi (LD) muscle of growing lambs by qPCR. Significant differences were found in the expression of GPX1, GPX2, SEPM, SEPW1, SEP15, SEPGS2, and TXNRD1 in the liver, and GPX1, SEPP1, SEPN1, SEPW1, SEP15, and MSRB1 in the LD muscle between S and C lambs. Se supplementation mainly upregulated SEPW1, SEP15 (P < 0.001; P < 0.01) mRNA expression in the liver, and GPX1, SEPP1, SEPN1, SEPW1 (P < 0.001; P < 0.01) in the muscle of S group. On the other hand, significant decrease in GPX2 (P < 0.01), SEPM (P < 0.001), and SEPHS2 (P < 0.01) mRNA expression levels were observed in the liver of S group of lambs. Se supplementation did not affect PON1, LXRα, and PPARα mRNA expression levels, but a significant increase in mRNA levels of APOE and LPL in the LD muscle (P < 0.05) as well as LPL (P < 0.05) in the liver were noticed in the group of Se supplemented lambs. Our study confirmed that, in lambs, similarly to other species, mRNA expression patterns of several selenoproteins highly depend on dietary Se levels, and their expression is ruled by hierarchical principles and tissue-specific mechanisms. Moreover, the study showed that changes Se intake leads to different levels of genes expression related with lipid metabolism.

The role of PON1 and CYP2D6 genes in susceptibility to organophosphorus chronic intoxication in Egyptian patients

BackgroundParaoxonase-1 (PON1) activity toward organophosphorus(OP) compounds shows inter-individual variations, rendering the identification of individuals’ PON1 allozymes valuable in treating patients suffering from organophosphorus intoxication. One of the most important cytochrome P450 monooxygenases (CYPs) is CYP2D6. The CYP2D6 G1934A polymorphism leads to good, poor or no enzyme activity. Genetic testing helps identification of high risk individuals as well as management of chronic intoxicated patients. Objectiveto investigate a possible association between genetic polymorphisms of PON1 Q192R, and CYP2D6 G1934A as well as PON1 and pseudo-cholinesterase (PChE) enzyme activity levels and chronic organophosphate exposed patients, and hence, susceptibility for organophosphorus chronic poisoning. Design and methodsThirty chronic organophosphate exposed farm workers were compared to 29 healthy controls as regards PON1 Q192R and CYP2D6 G1934A polymorphisms using PCR-RFLP technique. Also serum PON1 and PChE activities were determined spectrophotometrically. ResultsSerum PChE was significantly reduced in chronic intoxicated patients compared to the control group (p=0.02), while PON1 activity was increased, but just failed to reach significance (p=0.06). PON1 192 RR genotype and R allele were significantly increased in chronic OP intoxicated patients (p=0.005 &p=0.002 respectively). CYP2D6 1934A allele was significantly increased in chronic OP patients (p=0.045). combining the two SNPs showed a significant statistical difference between the two groups with PON1QQ and CYP2D6 GG genotypes being more represented in the healthy controls (p=0.001). Fatigue and motor weakness were the most prevalent neurological symptoms seen in chronic cases (56.7%), followed by headache and lacrimation (30% each), depression (23%), tingling and sensory symptoms (20%), sleep disorders and limb pain (13%).The mean duration of environmental exposure to organophosphates was 7.7±5.2years and no association was found between chronic symptoms of intoxication and duration of exposure, provided that all workers were exposed for at least 3 years. ConclusionPON1 192RR genotype and CYP2D6 1934A allele were found to be related to the susceptibility to organophosphate chronic toxicity in Egyptians. Larger scale gene-environmental interaction studies are recommended to confirm results and Genotyping is recommended during selection of agricultural pesticide workers to exclude high risk group.

Paraoxonase-1 in patients with type 2 diabetes mellitus who have had non-Q-myocardial infarction

Objective – to investigate the level of PON-1 in the serum of patients with type 2 DM who have hadnon-Q-MI.Materials and methods. The study involved 49 patients (average age of patients – 61,52 ± 1,41 years), of which 28 – patients with type 2 DM who have had non-Q-MI (main group), 10 patients who have had non-Q-MI without concomitant diabetes (I comparison group) and 11 patients with type 2 DM without a history of MI (II comparison group). The control group consisted of 10 healthy individuals. The concentration of PON-1 in the serum was determined by enzyme immunoassay using the analyzer-photometer iEMS Reader MF (Labsystems, Finland).Results and discussion. According to the results of the study it was revealed a significant increase in the concentration of PON-1 in the main group of patients (p &lt; 0.05) in comparison with CG. Herewith, there was a tendency to a lower concentration of PON-1 in diabetic postinfarction patients (p &lt; 0.2) compared with similar patients without diabetes mellitus. According to correlation analysis it was reverse correlation between the concentration of PON-1 and glycemia (r = –0,44, p&lt;0.02), HOMA index (r = –0.37, p &lt; 0.05), LP (a) – r = –0,48, p &lt; 0.01 and a direct dependence of the concentration of PON-1 from the level of IL-10 (r = 0,59, p &lt; 0.001).Conclusions. Post-MI patients with type 2 DM are characterized by the increased level of PON-1 in the serum. Herewith, the content of PON-1 has the opposite dependence on blood glucose, insulin resistance, concentrations of LP (a) and directly depends on the level of IL-10.

PON1 polymorphisms are predictors of ability to attain HDL-C goals in statin-treated patients

ObjectivesPON1 plays an important role in inhibiting LDL-C oxidation, which reduces atherosclerosis and cardiovascular disease. Elevated PON1 activity or levels may contribute to increased HDL-C levels, but controversy exists over the hypothesis that genetic variation in the PON1 gene locus modulates HDL-C levels and responses to statin treatment. Therefore, the objective of this study was to investigate the association between two polymorphisms in the PON1 gene and statin responses in a south Brazilian population. Design and methodsThe study population included 433 dyslipidemic patients who were prescribed statins. Total cholesterol, triglyceride, HDL-C and LDL-C levels were measured in these patients both before and after approximately 6months of treatment with simvastatin/atorvastatin. Genotypes were assessed by real-time PCR for two PON1 polymorphisms, Q192R (rs662) and L55M (rs854560). ResultsBaseline lipid levels were not associated with Q192R or L55M polymorphisms. For the Q192R (rs662) polymorphism, we observed that HDL-C goals were attained less often in patients with RR homozygosity than in Q allele carriers (χ2 P=0.009, adjusted residual analysis P=0.003). For the L55M (rs854560) polymorphism, LL homozygotes were underrepresented among subjects that achieved the HDL-C goal (χ2 P=0.026, adjusted residual analysis P=0.008). Analysis by univariate logistic regression confirmed that QQ/QR and MM/ML carriers had an increased chance of attaining HDL-C goals (OR=2.41, CI95%=1.32–4.40, P=0.004 and OR=1.68, CI95%=1.15–2.45, P=0.008). In a multivariate logistic analysis used to assess predictors of attaining an HDL-C goal>1.55mmol/L, we observed that gender (OR=1.71, CI95%=1.04–2.83, P=0.036), baseline HDL-C levels (OR=1.13, CI95%=1.10–1.16, P<0.001) and the QQ/QR+MM/ML genotypes increased the chance of achieving HDL-C goals (OR=2.81, CI95%=1.35–5.85, P=0.006). ConclusionsThe results of this study show that the Q192R (rs662) and L55M (rs854560) polymorphisms may play a role in interindividual variation in achievement of HDL-C goals in response to statins.

Lipid, Oxidative and Inflammatory Profile and Alterations in the Enzymes Paraoxonase and Butyrylcholinesterase in Plasma of Patients with Homocystinuria Due CBS Deficiency: The Vitamin B12 and Folic Acid Importance.

Cystathionine-β-synthase (CBS) deficiency is the main cause of homocystinuria. Homocysteine (Hcy), methionine, and other metabolites of Hcy accumulate in the body of affected patients. Despite the fact that thromboembolism represents the major cause of morbidity in CBS-deficient patients, the mechanisms of cardiovascular alterations found in homocystinuria remain unclear. In this work, we evaluated the lipid and inflammatory profile, oxidative protein damage, and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of CBS-deficient patients at diagnosis and during the treatment (protein-restricted diet supplemented with pyridoxine, folic acid, betaine, and vitamin B12). We also investigated the effect of folic acid and vitamin B12 on these parameters. We found a significant decrease in HDL cholesterol and apolipoprotein A1 (ApoA-1) levels, as well as in PON1 activity in both untreated and treated CBS-deficient patients when compared to controls. BuChE activity and IL-6 levels were significantly increased in not treated patients. Furthermore, significant positive correlations between PON1 activity and sulphydryl groups and between IL-6 levels and carbonyl content were verified. Moreover, vitamin B12 was positively correlated with PON1 and ApoA-1 levels, while folic acid was inversely correlated with total Hcy concentration, demonstrating the importance of this treatment. Our results also demonstrated that CBS-deficient patients presented important alterations in biochemical parameters, possibly caused by the metabolites of Hcy, as well as by oxidative stress, and that the adequate adherence to the treatment is essential to revert or prevent these alterations.

A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.

Study of Lipid profile and Paraoxonase-1 Activity in Psoriatic patients

Background: Psoriasis is a common recurrent disease of skin characterised by excessive cell proliferation and incomplete differentiation in lesional epidermis.Aim: The present study was aimed to determine lipid parameters and paraoxonase activity in psoriatic patients. Methods: The study included 100 subjects of age group 30-60 years, out of which 50 were patients of psoriasis (Case group) and rest 50 were normal healthy individuals of same age group (Control group).Result: Our study showed significant increase (p<0.001) in the levels of Cholesterol, Triglyceride, LDL and VLDL in patients of psoriasis as compared to control group. Also, we found significant decreased levels of serum HDL and PON-1 in psoriatic patients as compared to control group.Conclusion: Our study concludes that altered lipid profile and paraoxonase may be responsible for the higher prevalence of systemic complication such as metabolic and cardiovascular diseases.

Determination of PON1 Gene Polymorphisms in Iranian Individuals with High LDL/HDL Ratios

Elevated LDL/HDL ratio is an important risk factor for predicting atherosclerosis. Paraoxonase-1 protects LDLs from oxidative modifications and has a protective effect against atherosclerosis. Two common polymorphisms, Q192R and L55M, in PON1 gene can affect PON1 levels and function. The aim of this study was to evaluate the frequency PON1 polymorphisms in individuals with high and normal LDL/HDL ratios. To evaluate Q192R and L55M polymorphisms in Iranian case group (n = 70) with high LDL/HDL ratio, and control group (n = 80) with normal LDL/HDL ratio, we used PCR–RFLP method. Genotype frequencies for Q192R were 52.2 % for QQ, 46.3 % for QR, and 1.5 % for RR in case group (P = 0.003). However, Genotype frequencies in case group for L55M were 17.5 % LL, 75.3 % LM, and 7.2 % MM (P = 0.001). PON1 L55M polymorphism was associated with high LDL/HDL ratios in case group. So, the L55M polymorphisms can contribute in reducing the antioxidant function and decreasing level of HDL particles. In conclusion, PON1 L55M polymorphism can affect lipid metabolism and may be related to atherosclerosis in Iranian individuals.

Paraoxonase-1 enzyme activity assay for clinical samples: validation and correlation studies.

BackgroundParaoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to numerous pathophysiological disorders. It is a potential biomarker in many pathological conditions such as cardiovascular diseases.Material/MethodsWe conducted several small-scale studies to evaluate PON1 performance as affected by sample types, storage, and interferences. We also carried out short-term studies to compare the performance of the widely used PON1 assay to the similar commercially available PON1 kit assay method; sample size for the method comparison was N=40, and the number varied for other validation experiments.ResultsOur studies using various types of anticoagulants show that samples collected in tubes with NaF, citrate, EDTA, clot activator, and sodium heparin have increased PON1 levels that are 49%, 24.5%, 19.8%, 11.4%, and 8%, respectively, higher compared to serum samples collected in plain tubes. However, samples collected in lithium heparin tubes demonstrated 10.4% lower PON1 levels compared to serum collected in plain tubes. Biological interference such as hemolysis has little effect on PON1 levels; however, samples spiked with lipids have shown 13% lower PON 1 levels. Our studies comparing the PON1 method commonly available for PON1 assay and a similar non-ELISA commercially available PON1 kit method showed a weak Spearman correlation coefficient of R2=0.40 for the range of 104.9–245.6 U/L.ConclusionsThe current study provides new validation data on enzyme PON1 performance. While no appreciable change was seen with storage, samples type affects the enzyme performance. Our results should encourage additional clinical studies to investigate other aspects of factors known to affect PON1 enzyme function and performance.

The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children

Obesity is known to be associated with many diseases in the long and short terms. Elevated oxidative stress contributes to the development of such obesity-related diseases as dyslipidemia, diabetes mellitus and hypertension. Levels of the endogenous antioxidants paraoxonase and arylesterase have been shown to decrease in such diseases. The purpose of this study was to investigate whether or not changes in lifestyle and metformin therapy would affect serum paraoxonase and arylesterase levels. The study was performed with 25 overweight, 26 obese and 25 morbidly obese patients aged 6-15 years as well as 27 healthy children. Serum paraoxonase (PON1) and arylesterase (ARE) activity levels and total cholesterol, triglyceride, low-density protein, high-density protein, very low-density protein, glucose, aspartate amino transferase and alanine amino transferase levels were measured. Enrolled patients were assessed at initial presentation and again at 6 months. No procedure was performed in the control group, while the overweight, obese and morbidly obese groups were recommended diet and exercise and given metformin therapy (insulin-resistant subjects only). Serum PON1 activity levels in patients with metabolic syndrome were significantly lower than those in individuals without metabolic syndrome (p<0.05), while lipid concentrations were significantly higher (p<0.05). Metabolic syndrome patients had higher serum glucose, total cholesterol, low-density protein, very low-density protein and triglyceride values compared to those of the control group but significantly lower high-density protein values (p<0.05). No difference was determined between the groups in terms of PON1 and ARE levels following diet and exercise and metformin therapy. Measurement of PON1 and ARE enzyme levels may be useful in monitoring the effectiveness of treatment aimed at reducing oxidative stress in obese children.

Lack of Association of Paraoxonase 1 Promoter Polymorphisms with Gulf War Illness

Low serum PON1 levels are associated with Gulf War Illness (GWI). We sought to investigate the role of PON1 promoter polymorphisms in defining PON1 levels in GWI. There were no differences in the distribution of the PON1 -108 or PON1 -909 genotypes between the Gulf War Veterans (GWV) and the controls; however, PON1 activity and concentration were significantly lower in the GWV. In the control population, PON1 activity was significantly different between the PON1 -108 genotypes in the order CC>TC>TT (P GC>CC (P<0.001). However, in the GWV, such activity differences between genotypes were not evident. In the GWV PON1 activity was significantly lower in all the PON1 -108 and -909 genotypes compared to controls. There were no differences in PON1 concentration between any of the PON1 -108 or -909 genotypes in either population, however, the concentration was lower in all genotypes in the Veterans compared to the controls. Low serum PON1 levels appear to be related to symptoms of GWI independent of PON1 promoter and coding region polymorphisms. More studies with larger cohorts are required to define a role for PON1 in GWI.

Gender-specific association of oxidative stress and inflammation with cardiovascular risk factors in Arab population.

Background. The impact of gender difference on the association between metabolic stress and cardiovascular disease (CVD) remains unclear. We have investigated, for the first time, the gender effect on the oxidative and inflammatory stress responses and assessed their correlation with classical cardiometabolites in Arab population. Methods. A total of 378 adult Arab participants (193 females) were enrolled in this cross-sectional study. Plasma levels of CRP, IL-6, IL-8, TNF-α, ROS, TBARs, and PON1 were measured and correlated with anthropometric and cardiometabolite parameters of the study population. Results. Compared to females, males had significantly higher FBG, HbA1c, TG, and blood pressure but lower BMI, TC, and HDL (P < 0.05). After adjustment for BMI and WC, females had higher levels of ROS, TBARS, and CRP (P < 0.001) whereas males had increased levels of IL-8, IL-6, and TNF-α (P < 0.05). Moreover, after adjustment for age, BMI, and gender, the levels of TNF-α, IL-6, and ROS were associated with central obesity but not general obesity. Conclusion. Inflammation and oxidative stress contribution to CVD risk in Arab population linked to gender and this risk is better reflected by central obesity. Arab females might be at risk of CVD complications due to increased oxidative stress.

Measurement of activity and concentration of paraoxonase 1 (PON-1) in seminal plasma and identification of PON-2 in the sperm of boar ejaculates.

This study revealed and characterised the presence of the antioxidant enzymes paraoxonase (PON) type 1 (PON-1, extracellular) and type 2 (PON-2, intracellular) in boar semen. To evaluate PON-1, an entire ejaculate from each of ten boars was collected and the seminal plasma was harvested after double centrifugation (1,500g for 10 min). Seminal plasma was analysed for concentration as well as enzymatic activity of PON-1 and total cholesterol levels. Seminal-plasma PON-1 concentration ranged from 0.961 to 1.670 ng/ml while its enzymatic activity ranged from 0.056 to 0.400 IU/ml, which represent individual variance. Seminal-plasma PON-1 concentration and enzymatic activity were negatively correlated (r = -0.763; P < 0.01). The activity of seminal-plasma PON-1 negatively correlated with ejaculate volume (r = -0.726, P < 0.05), but positively correlated with sperm concentration (r = 0.654, P < 0.05). Total seminal-plasma cholesterol concentration positively correlated with PON-1 activity (r = 0.773; P < 0.01), but negatively correlated with PON-1 concentration (r = -0.709; P < 0.05). The presence of intracellular PON-2 was determined via immunocytochemistry in spermatozoa derived from artificial insemination. PON-2 localised to the post-acrosomal area of the sperm head and principal piece of the tail in membrane-intact spermatozoa. In summary, PON is present in boar semen, with PON-1 at low levels in seminal plasma and PON-2 within the spermatozoa. Further studies are needed to characterise the relationship between antioxidant PONs with sperm and other seminal-plasma parameters.

Plasma paraoxonase, oxidative status level, and their relationship with asthma control test in children with asthma

BackgroundAssessment of asthma with a control test has been suggested as a relevant approach in recent years. However, no biomarker of systemic inflammation has been included in the assessment of asthma control. ObjectiveTo evaluate plasma paraoxonase (PON1), total oxidant status (TOS), and total antioxidant status (TAS) levels in children with asthma according to the disease control, and the performance in the identification of uncontrolled patients. MethodsStable asthmatic children (n=85) and healthy controls (n=55) were recruited for this study. Blood samples were collected for plasma PON1, TOS, and TAS measurements. Any contributing factors that may affect plasma PON1, TAS, and TOS levels were excluded from both groups. The diagnostic potential of these measures was evaluated using receiver operating characteristic (ROC) analysis. ResultsComparing the asthmatic children with the control group, plasma TAS and TOS levels were significantly higher (TAS; 6.9±2.1, 1.05±0.32, P<0.001, and TOS; 12.5±3.4, 5.5±3.8, P<0.001, respectively) and PON1 level was significantly lower (156.5±55, 298.6±87.6, respectively, P<0.001) in the asthmatic group than controls. In ROC analysis, PON1 presented an AUC 0.679 and TOS presented an AUC 0.645 for the identification of uncontrolled asthma, respectively. Asthma Control Test (ACT) presented an AUC of 0.972 for the identification of uncontrolled asthma. ConclusionPON1 and TOS levels may be systemic markers of uncontrolled asthma in children. Combined use of these two biomarkers with asthma control test may identify patients with uncontrolled asthma in children.

Decreased level of serum paraoxonase (PON) activity in dogs with dilated cardiomyopathy (DCM)

Serum Paraoxonase (PON1) is a high-density lipoprotein associated esterase capable of hydrolyzing numerous organophosphates and protects low-density lipoprotein against peroxidation. PON1 is believed to play a crucial role in the prevention of cardiovascular disease in animals and PON1 activity has been shown to be low after myocardial infarction, liver disease and during oxidative stress. Here in this article we demonstrated that PON1 level is significantly lowered during the dilated cardiomyopathy (DCM) in dogs. This investigation was carried out on 208 canine serum samples. The serum PON/arylestrase activity was measured in 84 healthy dogs and 124 dogs with dilated cardiomyopathy (DCM) of varying severity. Since heart failure is characterized by oxidative stress, inflammation, deficiency in metabolic substrates and lack of blood supply to heart. Decreased PON activity was significantly observed in advanced stages of DCM. Key words: DCM, Paraoxonase, Phenyl acetate, High-density lipoprotein, NYHA-classification.

Roles for Paraoxonase but not Ceruloplasmin in Peritoneal Washing Fluid in Differential Diagnosis of Gynecologic Pathologies

Intraperitoneal spread of gynecologic cancers is a major cause of mortality and morbidity and often presents with malignant ascites. Microscopic tumor spread can be demonstrated by a peritoneal wash cytology and help assess the prognosis of the disease. In our study, the roles of paraoxonase and ceruloplasmin, measured in peritoneal washing fluid of patients operated for gynecologic pathologies in differential diagnosis was investigated. Patients operated for malign or benign gynecologic pathologies in Antalya Education and Research Hospital Gynecology Clinic between 2010-2012 were included in the study. Samples were obtained during surgery. A statistically significant difference was detected between patients with benign and malign diseases with regards to PON1 levels measured in peritoneal washing fluid (p:0.044), the average values being 64.2±30.8 (Range 10.8-187.2) and 41.4±21.4 (Range 10.4-95.5), respectively. No significant variation was evident for ceruloplasmin. Paraoxonase levels measured in peritoneal washing fluid may contribute to the differentiation of malign-benign diseases in gynecologic pathologies.

Urotensin-II level and its association with oxidative stress in early diabetic nephropathy

ObjectiveDiabetic nephropathy is the most common cause of end stage renal failure. Early treatment of diabetic nephropathy depends on understanding the underlying mechanisms of the disease. In this study we investigated the role of U-II in early nephropathy and ıts association with oxidative stress, paraoxonase (PON)-1 and arylesterase. Research design and methodsTwenty-three diabetic patients with microalbuminuria, 23 diabetic patients with normoalbuminuria and 25 healthy individuals were enrolled in the study. Serum total antioxidant status (TAS), total oxidant status (TOS), PON-1, arylesterase, and urotensin-II (U-II) levels were measured. Oxidative stress index (OSI) percent ratio of TOS to TAS level was accepted as OSI. ResultsSerum U-II levels were higher in the microalbuminuric diabetes group compared to the normoalbuminuric diabetic group and the healthy control group (p=0.009 and p=0.0001, respectively). Normoalbuminuric diabetic group's U-II levels were significantly higher compared to those of the healthy control group (p=0.0001). Correlation analysis yielded that plasma U-II levels are negatively correlated to TAS, arylesterase, and PON-1 levels (r=−0.395, p=0.001; r=−0.291, p=0.014; and r=−0.279, p=0.018, respectively) and that they had a positive correlation with OSI levels (r=0.312, p=0.008). These associations were confirmed in the multiple regression analysis. The results of multiple logistic regression analysis showed that oxidative stress is important in the development of microalbuminuria. ConclusionThe data of this study reveal that increased serum U-II has a role in the development of diabetic nephropathy. This effect of U-II may be related to high levels oxidative stress parameters.

Antioxidant status in blood of obese children: the relation between trace elements, paraoxonase, and arylesterase values.

Obesity is known to lead to complications involving several systems. The basic mechanism in obesity-related complications is chronic inflammation and increased oxidative stress. Trace element levels in obese children may vary due to poor nutritional habits. The purpose of this study was to investigate the relation between serum paraoxonase (PON1) and arylesterase (ARE) levels, markers of the oxidant-antioxidant balance in the body, and serum zinc (Zn), copper (Cu), manganese (Mn), and selenium (Se) concentrations in obese children. Fifty-seven overweight patients aged 6-17 and 48 age- and sex-matched healthy children were included in the study. Serum PON1 and ARE activity levels were measured, together with Cu, Zn, Mn, Se, total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, glucose, aspartate amino transferase, and alanine amino transferase levels. PON1 and ARE activity levels were significantly lower in obese patients compared to those in healthy individuals (P < 0.05). Various changes were determined in Cu, Zn, Mn, and Se levels between the study and control groups (P < 0.05). In terms of the relation between trace elements and PON1 and ARE levels, a significant positive correlation was determined between serum Se and PON1 levels in the study group (P < 0.05, r = 0.31). No significant correlation was determined between other trace element levels and PON1 and ARE levels (P > 0.05). In conclusion, the detection in our study of a positive correlation between Se and PON1 levels in obese children may be significant in terms of showing a relation between Se and antioxidant systems in obese children.

Oxidant and antioxidant parameters in prediabetes and diabetes

The aim of our study was to evaluate serum paraoxonase (PON1), total antioxidant status (TAS), total oxidant status (TOS), and ischemia-modified albumin (IMA) levels in patients with prediabetes, diabetes, and in healthy control subjects. The subjects were aged between 20 and 60 years. Forty diabetic subjects (mean age 46.6 ± 9.7 years), 39 prediabetic subjects (mean age 44.0 ± 9.3 years) and 24 healthy control subjects (mean age 43.7 ± 9.7 years). Lipid profile, PON1, TAS, TOS and IMA levels were measured. The serum TOS and IMA levels in diabetes were significantly higher than those of the control subjects (P = 0.024 and P = 0.012, respectively), while the serum PON1 levels of the diabetes patients were significantly lower than those of the control subjects (P = 0.039). The serum TOS levels of the diabetes patients were significantly higher than those of the subjects with prediabetes (P = 0.013). There were no significant differences between the serum IMA and PON1 levels of the prediabetes and diabetes groups (P = 0.075 and P = 0.110, respectively). The serum TAS levels of the three groups were similar. The present study demonstrated that in diabetes there is greater oxidative stress. Patients with type 2 diabetes had higher TOS and IMA levels, but lower PON1 values, than controls. There were no differences in oxidative stress markers between prediabetic patients and healthy subjects.

Curcumin antagonizes the effects of EPA and DHA supplementation on oxidative stress in dogs (246.7)

In obese dogs, some beneficial effects of PUFAs have been reported. They affect oxidative status as they stimulate endogenous antioxidant system, and are prone to be oxidized. The addition of a polyphenol antioxidant to an EPA+DHA supplement could be useful to better understand their mechanism of action.Our aim was to check the effects of EPA and DHA w/wo curcumin on hepatic gene expression in obese dogs.Animals were given a hyperenergetic diet with EPA+DHA (970 mg EPA/d and 780 mg DHA/d) for 6 wks, then EPA+DHA+curcumin for 6 wks. Liver biopsies were taken before (T0) and at the end of each period. The mRNA levels of antioxidant enzymes (SOD1, PON1, GPx, catalase, NQO1), of nuclear factor Nrf2 and hypoxia marker HIF1 α were assayed by RT‐PCR.At the end of the EPA+DHA supplementation, the mRNA levels of SOD1, Nrf2, PON1, GPx, catalase, NQO1 and Nrf2 were higher than at T0, whereas at the end of the EPA+DHA+curcumin supplementation, the expression was not modified. The expression of HIF1 α was lower at the end of the EPA+DHA supplementation, and unchanged at the end of the EPA+DHA+curcumin supplementation.Our results suggest that the PUFAs effects could be inhibited when curcumin was added. Nevertheless, these results do not permit to conclude if the higher expression of genes involved in antioxidant system reflects a defense against oxidized products, which generation could be avoided by the antioxidant curcumin.