Plasma Paraoxonase Research Articles

Plasma paraoxonase and arylesterase activities in smokers and smokeless tobacco users as Maraş powder

Context: Maraş powder (MP), a different type of smokeless tobacco (ST) prepared from a tobacco called Nicotiana rustica Linn, is widely used in the Southern Turkey. Smoking and ST cause oxidative stress (OS) in the human body. Paraoxonase (PON) and arylesterase (ARE) are antioxidant enzymes.Objective: To investigate the effects of MP on activities of PON, ARE, and malondialdehyde (MDA) levels in plasma and to compare these parameters in smokers and MP users (MPU).Materials and methods: The study consisted of smokers, MPU, and control group (CG) neither smoking nor using MP healthy subjects. PON and ARE activities were measured spectrophotometrically using paraoxon and phenylacetate substrates, respectively.Results: PON and ARE activities were decreased whereas MDA levels were increased in tobacco groups compared to the CG. The differences of ARE and MDA values between the tobacco groups and CG were found statistically significant (p < 0.01). But no significant differences were detected between the groups in the activity of PON (p > 0.05). However, the lowest activities of the enzymes were obtained in MPU.Conclusion: Our results can help to evaluate harmful effects of cigarette and ST as MP. These effects can be attributed to increased OS. Increased plasma MDA levels and decreased ARE activities may be important in assessing oxidant/antioxidant imbalance in MPU as well as smokers. Also, using of MP has harmful effects at least cigarette smoking.

Paraoxonase lactonase activity, inflammation and antioxidant status in plasma of patients with type 1 diabetes mellitus

To investigate paraoxonase-1 (PON1) lactonase activity, myeloperoxidase (MPO) activity (as a marker of inflammation) and antioxidant status in plasma of patients with type 1 diabetes mellitus. Whole blood and plasma samples were collected from patients with diabetes and healthy control subjects. PON1 lactonase and MPO activities and total antioxidant capacity (TEAC) were determined in plasma. Glycosylated haemoglobin (HbA1c) was quantified in whole blood. Plasma PON1 lactonase and MPO activities were significantly higher and TEAC was significantly lower in patients with diabetes (n = 18) compared with healthy control subjects (n = 20). There were significant positive correlations between PON1 lactonase activity and MPO activity and HbA1c level, and plasma MPO and HbA1c. There were significant negative correlations between PON1 lactonase activity and TEAC, and MPO activity and TEAC. Increased lactonase activity may inefficiently compensate for the high level of chronic inflammation and low antioxidant capacity in the plasma of patients with type 1 diabetes mellitus.

Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression and PON1 Q192R gene polymorphism–smoking interactions differentially predict the odds of major depression and bipolar disorder

BackgroundMajor depression and bipolar disorder are accompanied by the activation of immune-inflammatory and Oxidative and Nitrosative Stress (O&NS) pathways and lowered levels of antioxidants. Paraoxonase (PON)1 (EC 3.1.8.1) is an antioxidant bound to High Density Lipoprotein (HDL). Polymorphisms in the PON1 Q192R coding sequence determine three functional genotypes, i.e. 192QQ, 192QR and 192RR. AimsThis study was carried out to delineate the associations of plasma PON1 activity and functional PON1 Q192R genotypes in major depression and bipolar disorder. MethodsPON1 status that is plasma PON1 abundance and three functional PON1 Q192R genotypes were assayed in 91 major depressed and 45 bipolar patients and compared to 199 normal controls. ResultsMajor depression, but not bipolar disorder, was accompanied by lowered PON1 activity. PON1 activity was decreased by smoking and a diagnosis by genotype interaction (i.e. lower PON1 in major depression with the QQ genotype). Logistic regression showed that smoking by QQ genotype significantly increased the odds of bipolar disorder and that major depression was predicted by plasma PON1 activity, serum HDL cholesterol and interactions between genotype×smoking. DiscussionThe results suggest that lowered plasma PON1 activity is a trait marker of major depression and that PONQ192R gene–environment (smoking) interactions differentially predict the odds of depression and bipolar disorder. LimitationsAssociation studies are prone to a risk of false positive findings and replication is essential. ConclusionsThe findings suggest that there are differential PON1 Q192R functional genotype×environment interactions in major depression and bipolar disorder. The effects of lowered PON1 activity may contribute to increased O&NS and immune-inflammatory burden in depression. PON1 status may contribute to the comorbidity between depression and other immune- and O&NS-related disorders, e.g. cardiovascular disorder.

Prediction of hypertension and cardiovascular disease risk in North Indian geriatric population: a conundrum of senescence

Background: Aging has been found to be associated with various sorts of health complications. Therefore, the present study was designed to evaluate the plasma paraoxonase (PON), Nitric Oxide (NO), Total Antioxidant Activity (TAA), lipid peroxidation and serum uric acid levels in the blood samples of different age group subjects and to determine their relation in the prediction of hypertension and cardiovascular disease risk with senescence. Methods: Markers of antioxidant reserves (PON, TAA, and uric acid), lipid peroxidation and endothelial dysfunction were estimated in selected 120 healthy subjects by using standard methods. Out of 120 subjects, 80 individuals were categorized into two groups: group I (40-55 years) and group II (≥56 years) and statistically compared it with that of 40 younger controls (20-30 years). Results: Marked depletion in plasma PON and NO levels were observed in group I and II subjects as compared to healthy controls whereas plasma lipid hydroperoxide (LHP) and erythrocyte malondialdehyde levels (MDA) were increased significantly (P <0.05) in group I and II subjects. However, levels of plasma TAA and uric acid were altered significantly (P <0.05) only in group II subjects. In addition, PON levels were inversely correlated with endothelial dysfunction, lipid peroxidation and uric acid, and positively related with TAA. Conclusions: These findings reflect the importance of assessment of plasma paraoxonase, as excellent marker along with NO in early prediction of hypertension risk and its related cardiovascular complications in elderly. Therefore, antioxidant defence system of body should be boosted up with advancing of age in order to avert future complications.

Age-dependent paraoxonase 1 (PON1) activity and LDL oxidation in Wistar rats during their entire lifespan.

Paraoxonase 1 (PON1) is an HDL bound enzyme which plays a key role in the protection of LDL and HDL from oxidation by hydrolyzing activated phospholipids and lipid peroxide products. Oxidative stress plays a crucial role in the development of atherosclerosis by oxidation of LDL. This study was conducted to determine age-dependent changes in plasma PON1 arylesterase activity and LDL oxidation in rats during their entire lifespan. 48 Wistar strain rats were grouped in six different age groups (1, 4, 8, 12, 18, and 24 months). We observe a significant (P < 0.001) age-dependent decrease in plasma PON1 arylesterase activity correlating with increase in susceptibility of LDL oxidation and increase in plasma MDA level concomitantly with a significant (P < 0.001) decrease in plasma radical scavenging activity after 8 months. The reduction of PON1 and free radical scavenging activity with age could have a considerable impact on the increased incidence of atherosclerosis with age. Our observation of a significant decline in PON1 activity which correlates with increased LDL oxidation after 8 months of age is an interesting observation and needs further investigation.

An assessment of antioxidant status in patients with carbon monoxide poisoning.

Carbon monoxide poisoning (COP) is an important cause of mortality and morbidity worldwide. This study was to investigate the levels of serum paraoxonase (PON), arylesterase (ARYL), ceruloplasmin (Cp), and sulfhydryl (-SH) in the treatment of COP, and to further understand the pathophysiology of COP. This prospective study comprised 107 individuals with COP (group 1) and 50 healthy volunteers (group 2). Serum, plasma, and erythrocyte samples were taken on admission from all participants with COP. This process was repeated in the 90(th) and 180(th) minutes of treatment. Samples were taken from the control group only once. The levels of plasma PON, ARYL, Cp activity and -SH were measured in both groups. Age, gender, and carboxyhemoglobin level were not correlated with PON, ARYL, Cp, and -SH levels. PON, ARYL, and -SH levels were significantly decreased in group 1 compared with group 2. Conversely, Cp was significantly elevated in group 1 in contrast to group 2. Although ARYL was lower on admission in patients with COP than that was observed in the 90(th) and 180(th) minutes (P<0.001), Cp was higher on admission than at the other time points (P<0.001). Participants with COP had decreased levels of antioxidants (PON, ARLY, and -SH). COP represses the antioxidant system.

Oxidative Indices Correlate with Dyslipidemia and Pro-Inflammatory Cytokine Levels in Fluoride-Exposed Rats

The aim of this study was to establish the effects of fluoride on lipid metabolism and attendant inflammatory response by exposing rats to 50 mg L(-1) and 100 mg L(-1) of fluoride through drinking water for seven weeks. Both concentrations led to hypercholesterolemia while the 100 mg L(-1) concentration induced hypertriglyceridaemia. High density lipoprotein (HDL) cholesterol levels dropped in the exposed rats while interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05). Fluoride-exposed rats also had significantly higher levels of liver malondialdehyde (MDA) and plasma lipid hydroperoxide (LOOH) but lower plasma paraoxonase (PON1) activity. Oxidative stress indices correlated with pro-inflammatory cytokines and plasma cholesterol. In contrast, proinflammatory cytokines inversely correlated with plasma triglyceride, HDL cholesterol and PON1. Our results suggest that the association between fluoride exposure with cardiovascular diseases may be related to its ability to disturb lipid homeostasis, and trigger pro-inflammatory cytokines and oxidative stress.

Plasma paraoxonase 1 arylesterase activity in d-galactose-induced aged rat model: correlation with LDL oxidation and redox status

There is much evidence linking the involvement of oxidative stress in the pathogenesis of aging. Paraoxonase 1 (PON1) is an HDL-associated antioxidant enzyme that inhibits the oxidative modification of low-density lipoproteins (LDL). We have investigated the changes in plasma PON1 activity, LDL oxidation, radical scavenging activity and lipid peroxidation in D-galactose-induced aging rat model and also compared the results with 24-month naturally aged rats. Arylesterase activity of PON1, susceptibility of LDL for oxidation, plasma radical scavenging activity and plasma thiobarbituric acid reactive substances (TBARS) were measured in normal control rats (4-months-old control rats subjected to D-galactose-induced experimental aging, and 24-month-old naturally aged rats). There was a significant decrease in plasma PON1 arylesterase activity in both subcutaneous D-galactose-treated groups and 24-month-old aged rats (P < 0.05, for each). TBARS, an oxidative stress marker, was seen to increase in the experimental groups (P < 0.01). In both subcutaneous galactose-treated and naturally aged rats, there was a significant rise in plasma LDL oxidation (P < 0.05, for each). However, radical scavenging activity was decreased significantly (P < 0.01) in both groups, as compared to control. The D-galactose-induced rat model of aging mimics the naturally aged rat with reference to PON1 arylesterase activity and susceptibility to LDL oxidation. The results emphasize the importance of PON1 with respect to aging and its association with redox balance of the body.

Association of Paraoxonase 1 Gene Polymorphism and Enzyme Activity With Carotid Plaque in Rheumatoid Arthritis

To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients. Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P < 0.0001). Compared to patients with either the QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased risk of carotid plaque on multivariate analysis, controlling for traditional CV risk factors, high-sensitivity C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (P < 0.05). Additional multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P < 0.05). The current findings suggest a relationship of the genetic determinants and activity of paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA.

Dietary exposure to silver nanoparticles in Sprague–Dawley rats: Effects on oxidative stress and inflammation

Due to undesirable hazardous interactions with biological systems, we evaluated the effect of silver nanoparticles (AgNPs) intake on oxidative stress and inflammation. Rats received for 81 days a standard diet (Controls) or a standard diet plus 500 mg/d/kg BW AgNPs. We assayed plasma lipids, and oxidative stress was assessed by measuring liver and heart superoxide anion production (O₂°⁻) and liver malondialdehyde levels (MDA). Antioxidant status was appraised using plasma paraoxonase activity (PON), plasma antioxidant capacity (PAC) and liver superoxide dismutase activity (SOD). Liver inflammatory cytokines TNFα and IL-6 levels and plasma alanine aminotransferase (ALT) were assayed. Compared with Controls, AgNPs raised cholesterolemia (9.5%), LDL-cholesterol (30%), and lowered triglycerides (41%). They also increased liver (30%) and cardiac (41%) O₂°⁻ production, reduced PON activity (15%) and raised liver TNFα (9%) and IL-6 (∼12%). Plasma ALT activity rose (12%) after treatment with AgNPs. However, PAC and liver MDA and SOD activity were unchanged. These features indicate that exposure to 500 mg/d/kg BW of AgNPs results in liver damage by a dysregulation of lipid metabolism, highlighting liver and heart as the most sensitive organs to the deleterious effects. Our findings also demonstrate for the first time the oxidative and inflammatory effects of dietary AgNPs.

Susceptibility of knee osteoarthritis patients to develop cardiovascular disease - a clinical study

Background: Osteoarthritis (OA) is a process of progressive destruction of articular cartilage which makes the OA patients physically inactive and increases the probability to develop cardiovascular disease (CVD). Aim: The objectives of present study were to estimate atherogenic index, markers of oxidative stress and inflammation in knee OA patients of different Kellegren- Lawrence (KL) grade and clarify the probability of knee OA patients to develop future CVD risk with disease severity. Methodology: Atherogenic index, plasma paraoxonase, C-reactive protein (CRP) and erythrocyte malondialdehyde (MDA) levels were estimated by using standard methods in 55 - 70 years aged 76 knee OA patients categorized into three groups (on the basis of KL grading scale) and 24 healthy subjects (control group). The obtained values were compared statistically by using student’s t-test. Result: A significant reduction in the plasma paraoxonase and serum HDL cholesterol levels were observed in (p&lt;0.05) Group II &amp; III knee OA patients. Similarly, erythrocyte MDA, Total cholesterol/HDL ratio and plasma CRP levels were increased significantly in (p&lt;0.05) Group II and III knee OA patients. However, these levels were found to be altered insignificantly (p&lt;0.01) in Group I knee OA subjects as compared to controls. Conclusion: Thus, the probability of KL grade III and IV knee OA patients to develop future risk of CVD are more as characterized by elevated antherogenic index, systemic inflammation and oxidative stress and reflect the need of antioxodants supplementation along with drug of choice to reduce CVD risk in knee OA patients. DOI: http://dx.doi.org/10.3126/ajms.v4i3.8169 Asian Journal of Medical Sciences 4(2013) 62-68

Effect of exercise on plasma paraoxonase1 activity in rugby players: Dependance on training experience

ObjectivesThere are conflicting data on the influence of physical activity on paraoxonase1 (PON1) activity. The purpose of this study is to investigate the effect of maximal exercise (ME) on plasma paraoxonase (PON) and arylesterase (ARE) activity in elite rugby players. In addition, the influence of training experience and PON1 Q192R polymorphism on PON1 activity changes at ME was evaluated.MethodsTwenty-five elite rugby players ages 22.0 ± 3.71 years, consisting of 11 juniors – J (2–7 years of training) and 14 seniors – S (8–15 years of training), completed ME on a cycle ergometer. PON and ARE activity, ferric reducing activity of plasma (FRAP), uric acid (UA), and total bilirubin concentration, as well as thiobarbituric acid reactive substances and lipid profile were investigated in the plasma before, at the bout, and 30 minutes after ME.ResultsAt the bout of ME we found an increase in PON1 activities, ARE/high-density lipoprotein C ratio, TBil, and TChol. However, ARE activity changes were not observed in the group of rugby players training for ≤7 years. FRAP and UA increased later – 30 minutes after ME.ConclusionWe conclude that in rugby players PON1 changes during ME depend on age, body composition, and training experience. The influence of PON1 Q192R polymorphism on PON1 changes at ME remains debatable.

Oxidant/Antioxidant Status in Cases of Snake Bite

BackgroundSnake bites are an important cause of mortality and morbidity worldwide, especially in rural areas. ObjectiveThe aim of this study was to investigate serum paraoxonase (PON), arylesterase (ARLY), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity and lipid hydroperoxide (LOOH) and total sulfhydryl group (-SH) levels in patients with snake venom poisoning. MethodsThe study included 49 patients with snake bite envenomation (Group 1) and 39 healthy volunteers as the control group (Group 2). Plasma PON, ARLY, Cp, and MPO activity and LOOH and -SH levels were measured. Laboratory measurements of 20 patients with snake bite envenomation (Group 3) were performed again after treatment. ResultsPON and ARLY activity and -SH levels were significantly decreased in Group 1 compared with those in Group 2. Cp and MPO activity and LOOH levels were significantly elevated in Group 1 compared with those in Group 2. PON and ARLY activity were significantly elevated in Group 3 compared with those in Group 1. Cp and MPO activity and LOOH levels were significantly decreased in Group 3 compared with those in Group 1. ConclusionsPatients with snake bite envenomation had increased oxidants (MPO and LOOH) and decreased antioxidants (PON, ARLY, and -SH). Results obtained in this study demonstrate that snake bites are associated with a shift to oxidative status. Therapy with antioxidants can lead to an increase in the antioxidant defense system, and thus improvements in clinical symptoms.

Aronia melanocarpa (chokeberry) polyphenol–rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice

We hypothesized that a polyphenol-rich chokeberry extract (CBE) would modulate hepatic lipid metabolism and improve antioxidant function in apolipoprotein E knockout (apoE−/−) mice. ApoE−/− mice were fed diets containing 15% fat with 0.2% cholesterol alone or supplemented with 0.005% or 0.05% CBE for 4 weeks. CBE polyphenol content was determined by the total phenols, 4-dimethylaminocinnamaldehyde, and ultra high-performance liquid chromatography-mass spectrometry methods. The 0.05% CBE diet provided mice with mean daily doses of 1.2 mg gallic acid equivalents of total phenols, 0.19 mg anthocyanins, 0.17 mg phenolic acids, 0.06 mg proanthocyanidins (as catechin-equivalents), and 0.02 mg flavonols. The 0.05% CBE group had 12% less plasma total cholesterol concentrations than the control. Despite the hypocholesterolemic effect of CBE, hepatic mRNA levels of low-density lipoprotein receptor, hydroxyl-3-methylglutaryl coenzyme A reductase and cholesterol 7α-hydroxylase in CBE-fed mice were not significantly different from controls. Dietary CBE did not alter hepatic lipid content or the hepatic expression of genes involved in lipogenesis and fatty acid β-oxidation such as fatty acid synthase, carnitine palmitoyltransferase 1 and acyl-CoA oxidase. Plasma paraoxonase and catalase activities were significantly increased in mice fed 0.05% CBE. Both CBE diets increased hepatic glutathione peroxidase (GPx) activity but the 0.05% CBE group had 24% less proximal intestine GPx activity relative to controls. Thus, dietary CBE lowered total cholesterol and improved plasma and hepatic antioxidant function at nutritionally-relevant doses in apoE−/− mice. Furthermore, the CBE cholesterol-lowering mechanism in apoE−/− mice was independent of hepatic expression of genes involved in cholesterol metabolism.

Hepatocyte-specific Dyrk1a gene transfer rescues plasma apolipoprotein A-I levels and aortic Akt/GSK3 pathways in hyperhomocysteinemic mice

Hyperhomocysteinemia, characterized by high plasma homocysteine levels, is recognized as an independent risk factor for cardiovascular diseases. The increased synthesis of homocysteine, a product of methionine metabolism involving B vitamins, and its slower intracellular utilization cause increased flux into the blood. Plasma homocysteine level is an important reflection of hepatic methionine metabolism and the rate of processes modified by B vitamins as well as different enzyme activity. Lowering homocysteine might offer therapeutic benefits. However, approximately 50% of hyperhomocysteinemic patients due to cystathionine-beta-synthase deficiency are biochemically responsive to pharmacological doses of B vitamins. Therefore, effective treatments to reduce homocysteine levels are needed, and gene therapy could provide a novel approach. We recently showed that hepatic expression of DYRK1A, a serine/threonine kinase, is negatively correlated with plasma homocysteine levels in cystathionine-beta-synthase deficient mice, a mouse model of hyperhomocysteinemia. Therefore, Dyrk1a is a good candidate for gene therapy to normalize homocysteine levels. We then used an adenoviral construct designed to restrict expression of DYRK1A to hepatocytes, and found decreased plasma homocysteine levels after hepatocyte-specific Dyrk1a gene transfer in hyperhomocysteinemic mice. The elevation of pyridoxal phosphate was consistent with the increase in cystathionine-beta-synthase activity. Commensurate with the decreased plasma homocysteine levels, targeted hepatic expression of DYRK1A resulted in elevated plasma paraoxonase-1 activity and apolipoprotein A-I levels, and rescued the Akt/GSK3 signaling pathways in aorta of mice, which can prevent homocysteine-induced endothelial dysfunction. These results demonstrate that hepatocyte-restricted Dyrk1a gene transfer can offer a useful therapeutic targets for the development of new selective homocysteine lowering therapy.

Investigation of oxidative and antioxidative status in patients with diabetic cataracts

To investigate the oxidative and antioxidative status in diabetic patients with cataracts and nondiabetic patients with cataracts as compared to controls. Materials and methods: There were 149 subjects included in the present study. Blood was collected from type 2 diabetic patients suffering from cataracts (diabetic cataract; n = 42), senile nondiabetic patients suffering from cataracts (nondiabetic cataracts; n = 60), and healthy subjects of a control group (n = 47). Serum levels of total oxidant status (TOS), total antioxidant status (TAS), total thiol levels (TTLs), and paraoxonase 1 (PON1) were investigated in the samples. Results: TTLs were significantly reduced in diabetic cataract patients (444.8 µmol/L) compared with both nondiabetic cataract patients (525.1 µmol/L) and the control group (569.9 µmol/L). Plasma PON1 levels also were significantly reduced in diabetic cataract patients (241.9 U/L) relative to the control group (178.3 U/L). There were no statistically significant differences between TAS and TOS levels among groups. Conclusion: The present study demonstrates a significant reduction in serum TTLs and serum PON1 activities in diabetic cataract patients compared with controls. These findings represent a failure in the antioxidant system, which may be related to the cataractogenic process.

Plasma Paraoxonase Activity and Oxidative Stress and Their Relationship to Disease Severity in Children with Allergic Rhinitis

Oxidative stress may play a role in the pathophysiology of several diseases including allergic rhinitis (AR). In children with AR an antioxidant enzyme paraoxonase (PON1) has not been previously investigated. The aim of this study was to investigate plasma PON1 activity and plasma total oxidant status (TOS), which are in the form of plasma reactive oxidants, and their association with severity of disease in house-mite-sensitive children with AR. This study included 66 children with persistent AR and 40 healthy controls aged between 7 and 12 years old. Plasma PON1, TOS, and total serum immunoglobulin E (IgE) were measured. The nasal symptom scores and body mass index were evaluated at the time of blood collection. Mean serum PON1 levels were significantly lower and, TOS levels were higher in the patient group than in the control group (p ≤ 0.001 and p ≤ 0.002, respectively). A significant negative correlation was observed between serum levels of PON1 and nasal symptom scores. However, serum levels of TOS were correlated with nasal symptom scores positively. There were no correlations between levels of total IgE and levels of PON1 and TOS levels. Plasma PON1 and TOS levels may serve as predictors of disease severity in children with AR and both of them appear to be attractive candidates for modulating inflammation in AR.

Reduced Paraoxonase 1 Activity as a Marker for Severe Coronary Artery Disease

Paraoxonase-1 (PON1), a high-density-lipoprotein- (HDL-) associated enzyme, has the potential to protect against atherogenesis. We examine the relationships between plasma PON1 activity and the progression of atherosclerosis as well as coronary artery disease (CAD). Fasting blood samples were collected from female apolipoprotein E-deficient (apoE−/−) mice and 149 patients undergoing coronary angiography for the biochemical parameters measurement. The severity of CAD was defined using angiographic Gensini score (GSS). Compared to 3-month-old apoE−/− mice, aged mice had significantly lower PON1 activity, which is negatively correlated with the size of atherosclerotic lesion and plasma interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels. In study patients, PON1 activity was correlated with age, sex, and HDL-cholesterol, apolipoprotein AI, and high-sensitivity C-reactive protein (hs-CRP) levels and was significantly lower in CAD group than that in non-CAD control group. Interestingly, PON1 activity in severe CAD group (GSS > 40) was further significantly reduced compared to those in mild and moderate subgroups (GSS ≤ 40) (P < 0.01). There is a significant correlation between PON1 activity and the severity of CAD as assessed by GSS (r = −0.393, P < 0.001). PON1 activity may be a potential biomarker for the severity of CAD.

Effect of experimental hyperhomocysteinemia on plasma lipid profile, insulin sensitivity and paraoxonase 1 in the rat

Hyperhomocysteinemia (hHcy) is a well-known risk factor of cardiovascular diseases, however, the mechanism of its detrimental effect is incompletely understood. Some studies suggest that, paradoxically, hHcy may promote traditional risk factors such as hyperlipidemia. We examined the effect of experimental hHcy on plasma lipid profile, glucose and insulin concentrations as well as on high-density lipoprotein (HDL)-associated antiatherosclerotic enzyme, paraoxonase 1 (PON1). Hyperhomocysteinemia was induced by feeding male Wistar rats with diet enriched with methionine or diet enriched in methionine and deficient in folate, vitamin B6 and B12 for 8 weeks. These diets resulted in the 3.3- and 9.6-fold elevation of plasma Hcy, respectively. Plasma total and HDL-cholesterol, triglycerides and apolipoprotein A-I were similar in all groups. High-methionine diets had no effect on fasting plasma glucose but significantly increased fasting plasma insulin concentration indicating impaired ability of insulin to suppress hepatic glucose output. PON1 activity was unchanged in high methionine vitamin B-sufficient diet-fed rats, but was decreased by 30-40% toward various substrates in high methionine vitamin B-deficient diet-fed animals. The results indicate that hHcy has no effect on lipid metabolism, however, induces insulin resistance and, above certain Hcy level, PON1 deficiency. Impaired insulin signaling and reduced PON1 activity may contribute to detrimental effects of hHcy. Adipobiology 2012; 4: 77-84.

Vineatrol and Cardiovascular Disease: Beneficial Effects of a Vine-Shoot Phenolic Extract in a Hamster Atherosclerosis Model

We evaluated the effect of the intake of a grapevine-shoot phenolic extract (Vineatrol 30) on early atherosclerosis in hamsters fed a hyperlipidic diet. Golden Syrian hamsters received for 13 weeks either a standard diet, a high-fat (HF) diet, or the HF diet plus Vineatrol 30 at 0.04, 0.2, or 1.0 mg/(kg body weight/d). We measured plasma lipids and glucose, insulin, leptin and adiponectin, as well as liver TNF-α and IL-6 levels. Oxidative stress was assessed by measuring plasma paraoxonase activity (PON) and liver superoxide anion production (O(2)(•-)). The aortic fatty streak area (AFSA) was also determined. In comparison with HF group, we demonstrated that the highest dose of Vineatrol 30 was capable of decreasing AFSA (67%), insulinemia (40%), and leptinemia (8.7%), which were increased by the HF diet. We also showed increased O(2)(•-) production (35%) and a rise in levels of the liver proinflammatory cytokines TNF-α (22%) and IL-6 (21%), accompanied by a fall in PON activity (56%) due to the HF diet versus the standard diet. In contrast, except plasma adiponectin levels that are not changed, Vineatrol 30 treatment lowered AFSA (67%), O(2)(•-) production (36%), insulin resistance (42%), leptinemia (9%), liver TNF-α (18%) and IL-6 (15%), while it rose PON activity (29%). These findings demonstrate the preventive effects of polyphenols present in Vineatrol 30 in managing cardiovascular, metabolic, and inflammatory risk factors.