Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment.

BACKGROUND: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer's disease. OBJECTIVE: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI). METHODS: Individuals with MCI (n = 196, 76.8-years-old, 60% women) participating in a randomized, double-blind placebo-controlled trial (VITACOG) were assigned to receive a daily dose of folic acid (0.8 mg), vitamin B12 (0.5 mg) and B6 (20 mg) (n = 95) or placebo (n = 101) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of participants (n = 168) by MRI. PON1 status, including PON1 Q192R genotype, was determined by quantifying enzymatic activity of PON1 using paraoxon and phenyl acetate as substrates. RESULTS: In the placebo group, baseline phenylacetate hydrolase (PhAcase) activity of PON1 (but not paraoxonase activity or PON1 Q192R genotype) was significantly associated with global cognition (Mini-Mental State Examination, MMSE; Telephone Inventory for Cognitive Status-modified, TICS-m), verbal episodic memory (Hopkins Verbal Learning Test-revised: Total Recall, HVLT-TR; Delayed Recall, HVLT-DR), and attention/processing speed (Trail Making A and Symbol Digits Modalities Test, SDMT) at the end of study. In addition to PhAcase, baseline iron and triglycerides predicted MMSE, baseline fatty acids predicted SDMT, baseline anti-N-Hcy-protein autoantibodies predicted TICS-m, SDMT, Trail Making A, while BDNF V66M genotype predicted HVLT-TR and HVLT-DR scores at the end of study. B-vitamins abrogated associations of PON1 and other variables with cognition. CONCLUSION: PON1 is a new factor associated with impaired cognition that can be ameliorated by B-vitamins in individuals with MCI.

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study.

Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time-condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.

Microencapsulated Pomegranate Reverts High-Density Lipoprotein (HDL)-Induced Endothelial Dysfunction and Reduces Postprandial Triglyceridemia in Women with Acute Coronary Syndrome.

(1) Background: the composition of high-density lipoproteins (HDL) becomes altered during the postprandial state, probably affecting their functionality vis-à-vis the endothelium. Since acute coronary syndrome (ACS) in women is frequently associated with endothelial dysfunction, it is likely that HDL are unable to improve artery vasodilation in these patients. Therefore, we characterized HDL from women with ACS in fasting and postprandial conditions. We also determined whether microencapsulated pomegranate (MiPo) reverts the HDL abnormalities, since previous studies have suggested that this fruit improves HDL functionality. (2) Methods: Eleven women with a history of ACS were supplemented daily with 20 g of MiPo, for 30 days. Plasma samples were obtained during fasting and at different times, after a lipid load test to determine the lipid profile and paraoxonase-1 (PON1) activity. HDL were isolated by sequential ultracentrifugation to determine their size distribution and to assess their effect on endothelial function, by using an in vitro model of rat aorta rings. (3) Results: MiPo improved the lipid profile and increased PON1 activity, as previously reported, with fresh pomegranate juice. After supplementation with MiPo, the incremental area under the curve of triglycerides decreased to half of the initial values. The HDL distribution shifted from large HDL to intermediate and small-size particles during the postprandial period in the basal conditions, whereas such a shift was no longer observed after MiPo supplementation. Consistently, HDL isolated from postprandial plasma samples hindered the vasodilation of aorta rings, and this endothelial dysfunction was reverted after MiPo consumption. (4) Conclusions: MiPo exhibited the same beneficial effects on the lipid profile and PON1 activity as the previously reported fresh pomegranate. In addition, MiPo supplementation reverted the negative effects of HDL on endothelial function generated during the postprandial period in women with ACS.

Effect of yerba mate and green tea on paraoxonase and leptin levels in patients affected by overweight or obesity and dyslipidemia: a randomized clinical trial.

BACKGROUND: This study aimed to evaluate the effect of the intake of yerba mate (YM) and green tea (GT) on serum levels of leptin and paraoxonase-1 (PON-1), compared to control. METHODS: Controlled, randomized clinical trial (RCT) that evaluated 142 men and women affected by overweight or obesity aged 35-60 years, untreated dyslipidemia and no history of coronary artery disease. Participants were randomized to ingest 1000 mL GT, YM or apple tea (AT, control group) daily, during eight weeks. Serum PON-1 and leptin levels were analyzed by ELISA immunoassay at the beginning (baseline) and after eight weeks of intervention. RESULTS: The intake of 1 l of YM/day resulted in significant increase in serum levels of PON-1 (9.7%; p = 0.005). The consumption of GT induced no significant difference in the levels of PON-1 (p = 0.154) and leptin (p = 0.783). Intergroup analysis showed a significant difference (p = 0.036) in the variation of PON-1 levels in the YM group when compared to GT and AT groups. In addition, the increase in PON-1 levels in the YM group was significantly associated with increased HDL-c (p = 0.004). CONCLUSIONS: The intake of yerba mate increased the antioxidant capacity by increasing serum levels of PON-1 and was positively associated with increased HDL-c, stressing the protective role of this beverage against atherosclerotic diseases. GT intake had no significant effect on serum levels of PON-1 and leptin. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov under protocol number NCT00933647.

Effect of combined vitamin D administration plus dietary intervention on oxidative stress markers in patients with metabolic syndrome: A pilot randomized study.

BACKGROUND: Metabolic syndrome (MetS) patients can have low 25-hydroxyvitamin D 25(OH)VitD levels, which may be associated with increased oxidative stress. There is little data on the effect of 25(OH)VitD administration plus dietary intervention on oxidative stress markers in these patients. AIM: To study the effect of 25(OH)VitD administration plus dietary intervention on oxidative stress markers in MetS patients. METHODS: This is a pre-specified analysis of a previously published study (NCT01237769 ClinicalTrials.gov). MetS participants (n = 50, 52 ± 10 years) were given dietary instructions and were randomized to 25(OH)VitD 2.000 IU/day p.o. (Suppl group) or no supplementation (No-Suppl group). Serum 25(OH)VitD, oxidized LDL (ox-LDL), paraoxonase activity (PON-1), arylesterase activity (ARYL) and urine 8-isoprostane (8-iso-PGF2a) levels were measured at baseline and after 3 months. RESULTS: MetS patients had low baseline 25(OH)VitD levels, which increased by 90% in the Suppl group [from 16.1 (3.3-35.1) to 30.6 (8.4-67.6) ng/mL, p = 0.001] and by 33.3% in the No-Suppl group [from 9.9 (4.0-39.6) to 13.2 (3.5-36.8) ng/mL, p = NS] after intervention. Ox-LDL, PON-1 and ARYL did not change significantly at follow-up in both groups, except for urine 8-iso-PGF2a levels that decreased by 22.7% in the Suppl group [from 48.8 (26.8-137.1) to 37.7 (12.3-99.0) ng/mmol creatinine, p = 0.015] and by 14.4% in No-Suppl group [from 45.8 (16.6-99.3) to 39.2 (13.3-120.1) ng/mmol creatinine, p = NS]. The reduction in 8-iso-PGF2a levels did not differ significantly between the 2 groups. CONCLUSION: The administration of 25(OH)VitD plus dietary intervention in patients with MetS was not associated with meaningful reductions in oxidative stress markers compared with dietary intervention alone.

Effects of Freeze-Dried Grape Powder on High-Density Lipoprotein Function in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Study.

BACKGROUND: High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. METHODS: Twenty adults (age: 32-70 years; body mass index: 25.3-45.4 kg/m2) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. RESULTS: After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo (P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. CONCLUSIONS: Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.

The barberry juice effects on metabolic factors and oxidative stress in patients with type 2 diabetes: A randomized clinical trial.

AIM: The aim of this study was to investigate the effect of barberry juice (BJ) on cardiovascular risk factors in patients with type 2 diabetes (T2DM). METHODS: 46 diabetic Patients were randomly allocated to either the BJ group (n = 23) who consumed 200 ml of BJ daily for eight weeks, or the control group (n = 23) with no intervention. At the baseline and the end of 8-week intervention, blood pressure and biochemical markers were measured. RESULTS: forty-two Patients completed the study. After intervention systolic blood pressure (SBP), diastolic blood pressure (DBP), Fasting Blood Sugar (FBS) Total Cholesterol significantly decreased (P < 0.05 for treatment effect) also Triglyceride (TG) decrease significantly in BJ group. Paraoxonase-1(PON1) concentrations significantly increased in Bj group and have a significant difference (P < 0.0001 for treatment effect) compared with control group. CONCLUSIONS: This study revealed that BJ might decrease the risk of cardiovascular diseases in patients with diabetes.

Daily supplementation with fresh pomegranate juice increases paraoxonase 1 expression and activity in mice fed a high-fat diet.

PURPOSE: Studies have found that pomegranate juice (PJ) consumption increases the binding of high-density lipoproteins (HDL) to paraoxonase 1 (PON1), thus increasing the catalytic activity of this enzyme. PON1 is an antioxidant arylesterase synthesized in the liver and transported in plasma in association with HDL. Decreased levels of PON1 are associated with higher levels of cholesterol. We determined the effects of PJ on body weight, cholesterol, and triacylglycerols through 5 months of supplementation. In addition, the effect of PJ on pon1 gene expression in the liver was also measured by RT-qPCR as well as the activity in serum by a semiautomated method using paraoxon as a substrate. METHODS: CD-1 mice were either fed a control diet or were fed a high-fat diet 1.25% (wt/wt) cholesterol, 0.5% (wt/wt) sodium cholate, and 15% (wt/wt) saturated fat. 300 µL of PJ containing 0.35 mmol total polyphenols was administered by oral gavage to half of the high fat mice daily. The rest of the high fat mice and the control mice were administered with 300 µL of water. RESULTS: PJ-supplemented animals had significantly higher levels of expression of pon1 compared to the unsupplemented group. PJ-supplemented animals had twice the PON1 activity of the unsupplemented group. In addition, PJ-supplemented animals had the lowest body weight and significantly reduced cholesterol and triacylglycerol levels, although the tricylglycerol levels were not consistently decreased. CONCLUSIONS: These results suggest that PJ protects against the effects of a high-fat diet in body weight, and cholesterol levels.

The Effect of Eicosapentaenoic Acid on the Serum Levels and Enzymatic Activity of Paraoxonase 1 in the Patients With Type 2 Diabetes Mellitus.

Paraoxonase 1 is known as one of the most important ant oxidative enzymes associated with HDL-c, and because of its antioxidant and antiinflammatory activities. EPA has the antioxidant, anti inflammatory, antithrombogenic, and antiarteriosclerotic properties. Therefore, we investigated the effect of EPA supplementation on the serum levels and activity of PON1 in type 2 diabetic patients. This study was designed as a randomized, double-blind, and placebo-controlled clinical trial. Thirty-six patients with type 2 diabetes were given written; informed consent randomly was classified into 2 groups. They were supplemented with 2 g/day of the capsules of EPA or placebo for eight weeks. Blood sample was given for measurement of the serum levels of lipids, the activity of PON1, FBS and HbA1c. The patients supplemented with EPA showed a significant increase in the serum levels and activity of PON1 and the serum ratio of PON1/HDL-c. There were no significant differences between the two groups regarding any demographic, clinical or biochemical data, total energy intake, and macronutrient intake at the baseline during the intervention, except for a significant increase of protein intake and the levels of HbA1c in the placebo group, and a significant increase of HDL-c, as well as a slight reduction of total cholesterol, LDL-c, TG and FBS in the supplement group. EPA is atheroprotective via increase in the serum levels and activity of PON1, as well as change in the serum levels of lipids, FBS and HbA1c.

The effects of green cardamom on blood glucose indices, lipids, inflammatory factors, paraxonase-1, sirtuin-1, and irisin in patients with nonalcoholic fatty liver disease and obesity: study protocol for a randomized controlled trial.

BACKGROUND: The relationship between dietary components and nonalcoholic fatty liver disease (NAFLD) needs to be further investigated. The potential health benefits of cardamom have been found in some studies. Cardamom showed beneficial effect on hepatomegaly, dyslipidemia, and fasting hyperglycemia in animals. However, some adverse effects of cardamom have been reported in animals. No previous human study had been conducted on the effects of cardamom in NAFLD. This study aims to determine the effects of green cardamom (Elettaria cardamomum) supplementation on blood glucose indices, lipids, inflammatory profiles, and liver function, especially by examining irisin, paraxonase-1 (PON1) and sirtuin-1 (Sirt1) in obese patients with NAFLD. METHODS: This trial is to be conducted at the polyclinic of the National Iranian Oil Company (NIOC) Central Hospital, Tehran. Eighty obese patients with NAFLD will be selected according to the eligibility criteria. The NAFLD diagnosis method is ultrasonography. Patients will be randomly divided into two groups by a random-number table (cardamom and placebo groups, two 500-mg capsules, three times/day, taken with meals for 3 months, follow-up monthly). General characteristics, dietary intakes (at the beginning, middle, and end), and physical activity (at the beginning and end) will be assessed using a general, 24-h food recall, and short-form International Physical Activity Questionnaires (IPAQ), respectively. Lifestyle advice will be presented to both groups identically. At the beginning and the end, anthropometrics (weight, height, and waist circumference), blood pressure, extent of fatty liver, and blood biomarkers, including serum glucose indices (fasting blood sugar (FBS)) and insulin (FBI), homeostasis model assessment-insulin resistance (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)), lipids (triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), total cholesterol (TC)), inflammatory markers (highly sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)), liver enzymes (alanine transaminase (ALT), aspartate transaminase (AST)), irisin, PON1, and Sirt1, will be determined. DISCUSSION: This trial would be the first to assess the effects of green cardamom on several blood factors, including glucose indices, lipids, inflammatory markers, liver enzymes, irisin, PON1, and Sirt1, and blood pressure and anthropometry in obese patients with NAFLD. Further study of cardamom's potential in improving NAFLD is suggested. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), ID number: IRCT2015121317254N4 . Registered on 27 December 2015.

Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats.

Combination therapy using natural antioxidants to manage diabetes mellitus and its complications is an emerging trend. The aim of this study was to investigate the changes promoted by treatment of streptozotocin (STZ)-diabetic rats with yoghurt enriched with the bioactives curcumin, lycopene, or bixin (the latter two being carotenoids). Antioxidants were administered individually, or as mixtures, and biomarkers of metabolic and oxidative disturbances, particularly those associated with cardiovascular risk, were assessed. Treatment of STZ-diabetic rats with natural products individually decreased glycemia, triacylglycerol, total-cholesterol, oxidative stress biomarkers, including oxidized low-density lipoprotein (ox-LDL), and increased the activities of antioxidant enzymes. Individual carotenoids increased both high-density lipoprotein (HDL) and paraoxonase levels, whereas curcumin increased only paraoxonase. Treatments with mixtures of curcumin and lycopene or bixin had combined effects, decreasing biomarkers of carbohydrate and lipid disturbances (curcumin effect), increasing the HDL levels (carotenoids effects) and mitigating oxidative stress (curcumin and carotenoids effects). The combined effects also led to prevention of the LDL oxidation, thereby mitigating the cardiovascular risk in diabetes. These findings provide evidence for the beneficial effect of curcumin and carotenoid mixtures as a supplementation having antioxidant and antiatherogenic potentials, thus appearing as an interesting strategy to be studied as a complementary therapy for diabetic complications.

The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases.

Low levels of paraoxonase 1 (PON1) have been associated with the development of several pathological conditions, whereas high levels have been shown to be anti-atherosclerotic in mouse models. These findings suggest that PON1 could be a good surrogate biomarker. The other members of the family, namely PON2 and PON3, the role of which has been much less studied, deserve more attention. This paper provides a systematic review of current evidence concerning dietary supplements in that regard. Preliminary studies indicate that the response to dietary supplements may have a nutrigenetic aspect that will need to be considered in large population studies or in clinical trials. A wide range of plant preparations have been found to have a positive action, with pomegranate and some of its components being the best characterized and Aronia melanocarpa one of the most active. Flavonoids are found in the composition of all active extracts, with catechins and genistein being the most promising agents for increasing PON1 activity. However, some caveats regarding the dose, length of treatment, bioavailability, and stability of these compounds in formulations still need to be addressed. Once these issues have been resolved, these compounds could be included as nutraceuticals and functional foods capable of increasing PON1 activity, thereby helping with the long-term prevention of atherosclerosis and other chronic ailments.

Comparison of Pure Palm Olein Oil, Hydrogenated Oil-Containing Palm, and Canola on Serum Lipids and Lipid Oxidation Rate in Rats Fed with these Oils.

BACKGROUND: Due to increased consumption of canola oil and hydrogenated oil containing palm and palm olein, and their possible effects on serum lipoproteins, the present study was conducted to determine the effects of these oils on lipids and lipid oxidation level. METHODS: In this experimental study, 88 Wistar rats were randomly assigned to four groups. Control group (A) was on a normal diet. Groups B, C, and D, in addition to normal diet, were fed with hydrogenated oil-contained palm oil, pure palm olein oil, and canola oil, respectively for 4 weeks. Serum Biochemical factors [total cholesterol (TC), triglyceride (TG), LDL, HDL, LDL/HDL ratio, oxLDL, paraoxanase-1 (PON1), and malondialdehyde (MDA)] were measured. RESULTS: The lowest mean serum TC was seen in the control group and the highest in the group B. There were differences in TC, TG, HDL, MDA, and PON1 between the control group and other groups (P<0.001). The lowest and highest LDL/HDL ratios were observed in the group C and the control group, respectively. Significant differences were seen in OxLDL and PON1 between the control group and other three groups (P<0.05), while there were no significant differences in oxLDL and PON1 among the other three groups (P>0.05). MDA was higher in groups C and D. CONCLUSION: Canola oil, hydrogenated oil-containing palm and palm olein may increase atherosclerosis risk through decreasing PON1 activity and elevating oxLDL. Palm olein oils in rats' diets cause a considerable decrease in LDL and help to increase HDL.

Protective effects of Xiongshao Capsule () on anti-inflammatory function of high-density lipoprotein in an atherosclerosis rabbit model.

OBJECTIVE: To observe the effects of Xiongshao Capsule (, XSC) on anti-inflflammatory properties of high-density lipoprotein (HDL), myeloperoxidase (MPO) and paraoxonase 1 (PON1) in serum of atherosclerosis (AS) rabbit model and explore the anti-inflflammatory protective effects of XSC on HDL. METHODS: Sixty rabbits were randomized into the control, the model, XSC low-, medium- and high-dose (Rhizoma Chuanxiong + Radix Paeoniae rubra: 0.6+0.3, 1.2+0.6, 2.4+1.2g·kg-1·day-1, respectively), and simvastatin (1g·kg-1·day-1) groups. The model rabbits were fed with high-fat diet and drugs for 15 weeks. The blood and thoracic aortas samples were collected at the end of 15 weeks. The levels of serum MPO and PON1 as well as total cholesterol (TC) and free cholesterol (FC) in aorta wall cells were tested by enzyme linked immunosorbent assay. RESULTS: TC and FC in the model group were significantly higher than those in the control group (P<0.01). Compared with the model group, TC and FC in the XSC groups were signifificantly lower (P<0.05 or P<0.01), so was simvastatin group (P<0.01). There was no signifificant difference in PON1 level between groups (P>0.05), even between model and control groups (P>0.05). The serum MPO level in the model group was signifificantly higher than that in the control group (P<0.05), which was signifificantly lower in XSC groups as well as simvastatin group (P<0.05 or P<0.01), and no difference was found between XSC groups and simvastatin group (P>0.05). CONCLUSIONS: XSC can reduce the serum MPO level in AS rabbits to protect the anti-inflammatory function of HDL, maintaining the normal lipid transport function. TC and FC levels in aorta cells decline, and this process initiated by XSC plays an anti-AS role.

Reduction in serum paraoxonase level in newborns with hyperbilirubinemia as a marker of oxidative stress.

OBJECTIVE: Indirect bilirubin exerts an antioxidant effect when increased mildly. This study aimed to investigate whether increased bilirubin levels lead to an oxidant effect in newborns with hyperbilirubinemia requiring phototherapy. PATIENTS AND METHODS: The study included 30 term newborn infants aged 0-7 days with indirect hyperbilirubinemia requiring phototherapy and no comorbid disease as the study group. In addition, 30 term healthy newborn infants aged 0-7 days without indirect hyperbilirubinemia were employed as a control group. Serum triglyceride, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), serum paraoxonase (PON) levels and malondialdehyde (MDA) levels were compared between the groups. RESULTS: Serum MDA, total bilirubin, and LDL and HDL levels were significantly higher and the serum PON level was significantly lower, in the study group compared with the controls (p < 0.05). CONCLUSION: In newborns with hyperbilirubinemia requiring phototherapy, an increased bilirubin level causes oxidative stress by decreasing the level of serum PON and increasing the level of MDA.

Rumen-protected methionine compared with rumen-protected choline improves immunometabolic status in dairy cows during the peripartal period.

The immunometabolic status of peripartal cows is altered due to changes in liver function, inflammation, and oxidative stress. Nutritional management during this physiological state can affect the biological components of immunometabolism. The objectives of this study were to measure concentrations of biomarkers in plasma, liver tissue, and milk, and also polymorphonuclear leukocyte function to assess the immunometabolic status of cows supplemented with rumen-protected methionine (Met) or choline (CHOL). Forty-eight multiparous Holstein cows were used in a randomized complete block design with 2×2 factorial arrangement of Met (Smartamine M, Adisseo NA, Alpharetta, GA) and CHOL (ReaShure, Balchem Inc., New Hampton, NY) level (with or without). Treatments (12 cows each) were control (CON), no Met or CHOL; CON and Met (SMA); CON and CHOL (REA); and CON and Met and CHOL (MIX). From -50 to -21d before expected calving, all cows received the same diet [1.40Mcal of net energy for lactation (NEL)/kg of DM] with no Met or CHOL. From -21d to calving, cows received the same close-up diet (1.52Mcal of NEL/kg of DM) and were assigned randomly to each treatment. From calving to 30d, cows were on the same postpartal diet (1.71Mcal of NEL/kg of DM) and continued to receive the same treatments until 30d. The Met supplementation was adjusted daily at 0.08% DM of diet, and CHOL was supplemented at 60g/cow per day. Liver (-10, 7, 21, and 30d) and blood (-10, 4, 8, 20, and 30d) samples were harvested for biomarker analyses. Neutrophil and monocyte phagocytosis and oxidative burst were assessed at d 1, 4, 14, and 28d. The Met-supplemented cows tended to have greater plasma paraoxonase. Greater plasma albumin and IL-6 as well as a tendency for lower haptoglobin were detected in Met- but not CHOL-supplemented cows. Similarly, cows fed Met compared with CHOL had greater concentrations of total and reduced glutathione (a potent intracellular antioxidant) in liver tissue. Upon a pathogen challenge in vitro, blood polymorphonuclear leukocyte phagocytosis capacity and oxidative burst activity were greater in Met-supplemented cows. Overall, liver and blood biomarker analyses revealed favorable changes in liver function, inflammation status, and immune response in Met-supplemented cows.

Açai (Euterpe oleracea Mart.) Upregulates Paraoxonase 1 Gene Expression and Activity with Concomitant Reduction of Hepatic Steatosis in High-Fat Diet-Fed Rats.

Açai (Euterpe oleracea Mart.), a fruit from the Amazon region, has emerged as a promising source of polyphenols. Açai consumption has been increasing owing to ascribed health benefits and antioxidant properties; however, its effects on hepatic injury are limited. In this study, we evaluated the antioxidant effect of filtered açai pulp on the expression of paraoxonase (PON) isoforms and PON1 activity in rats with nonalcoholic fatty liver disease (NAFLD). The rats were fed a standard AIN-93M (control) diet or a high-fat (HF) diet containing 25% soy oil and 1% cholesterol with or without açai pulp (2 g/day) for 6 weeks. Our results show that açai pulp prevented low-density lipoprotein (LDL) oxidation, increased serum and hepatic PON1 activity, and upregulated the expression of PON1 and ApoA-I in the liver. In HF diet-fed rats, treatment with açai pulp attenuated liver damage, reducing fat infiltration and triglyceride (TG) content. In rats receiving açai, increased serum PON1 activity was correlated with a reduction in hepatic steatosis and hepatic injury. These findings suggest the use of açai as a potential therapy for liver injuries, supporting the idea that dietary antioxidants are a promising approach to enhance the defensive systems against oxidative stress.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: 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). DESIGN AND SETTINGS: 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. RESULTS: 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. CONCLUSION: 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.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

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

CONTEXT AND OBJECTIVE: 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). DESIGN AND SETTINGS: 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. RESULTS: 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. CONCLUSION: 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.

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.