Total antioxidant capacity in beta-thalassemia: a systematic review and meta-analysis of case-control studies

otal Antioxidant Capacity (TAC), a biomarker measuring the antioxidant potential of body fluids, including redox synergistic interactions, is influenced by the presence of products of catabolism such as bilirubin (BR) and uric acid (UA). Hyperuricaemia and increased BR levels were observed in thalassemia. In order to evaluate the differences in TAC values between thalassemic patients and healthy subjects, we performed a systematic review and meta-analysis of case-control studies. After the exclusion of data deemed unsuitable for meta-analysis inclusion and a study imputed of bias by Trim-and-fill analysis, mean difference (MD) and confidence intervals 95% (CI 95%) were calculated by the random effect model for beta-thalassemia major (BTM) (1351 subjects: 770 thalassemic and 581 controls, from 15 studies) and Trait (BTT) or Hemoglobin E (BTE) (475 subjects: 165 thalassemic and 310 controls, from 5 studies). Despite the differences in clinical symptoms and severity, similar decreased levels of TAC were found in BTM [MD -0.22 (-0.35 -0.09) p < 0.001] and BTT or BTE [MD -0.22 (-0.44 -0.01) p < 0.05]. In conclusion, UA and BR interference on TAC suggests that corrected TAC and in particular the UA-independent TAC, considering the prominent influence of UA, might be the better approach to evaluate body antioxidant status. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Relationship between the peroxidation of leukocytes index ratio and the improvement of postprandial metabolic stress by a functional food

For the first time, we investigated the relationship between postprandial dysmetabolism and the Peroxidation of Leukocytes Index Ratio (PLIR), a test that measures the resistance of leukocytes to exogenous oxidative stress and their functional capacity of oxidative burst upon activation. Following a blind, placebo controlled, randomized, crossover design, ten healthy subjects ingested, in two different occasions, a high fat and high carbohydrates meal with Snello cookie (HFHCM-S) or with control cookies (HFHCM-C). Snello cookie, a functional food covered by dark chocolate and containing glucomannan, inulin, fructooligosaccharides, and Bacillus coagulans strain GanedenBC30, significantly improved postprandial metabolic stress (insulin, glucose, and triglycerides) and reduced the postprandial increase of uric acid. HFHCM-S improved PLIR of lymphocytes, but not of monocytes and granulocytes. Both meals increased granulocytes' count and reduced the lipoperoxidation induced by both exogenous free radicals and reactive oxygen species (ROS) produced by oxidative burst. Our results suggest that the healthy status of the subjects could be a limitation of this pilot study for PLIR evaluation on cells that produce ROS by oxidative burst. In conclusion, the relationship between PLIR and postprandial dysmetabolism requires further investigation

The peroxidation of leukocytes index ratio reveals the prooxidant effect of green tea extract

Despite tea increased plasma nonenzymatic antioxidant capacity, the European Food Safety Administration (EFSA) denied claims related to tea and its protection from oxidative damage. Furthermore, the Supplement Information Expert Committee (DSI EC) expressed some doubts on the safety of green tea extract (GTE). We performed a pilot study in order to evaluate the effect of a single dose of two capsules of a GTE supplement (200mg x 2) on the peroxidation of leukocytes index ratio (PLIR) in relation to uric acid (UA) and ferric reducing antioxidant potential (FRAP), as well as the sample size to reach statistical significance. GTE induced a prooxidant effect on leukocytes, whereas FRAP did not change, in agreement with the EFSA and the DSI EC conclusions. Besides, our results confirm the primary role of UA in the antioxidant defences. The ratio based calculation of the PLIR reduced the sample size to reach statistical significance, compared to the resistance to an exogenous oxidative stress and to the functional capacity of oxidative burst. Therefore, PLIR could be a sensitive marker of redox status

Oxidative stress in the metabolic syndrome and the evaluation of the Peroxidation of Leukocytes Index Ratio

Based on the potential protective effects against the onset of metabolic syndrome (Peluso et al. 2014a), functional foods containing probiotics, prebiotics, and/or polyphenols were placed on the market. Improvement of metabolic profile, oxidative stress, and inflammation has been reported also for glucomannan (Sood et al 2008; Bauerova et al. 2008). De Luis et al. (De Luis et al. 2011) pointed out that one of the problems of dietetic therapy is the lack of patient adherence and suggested that one possibility to overcome this problem is to include functional cookies in the diet. In particular, significant decreases of cholesterol and C reactive protein were observed in obese patients after the consumption of an alpha linolenic acid, fructooligosaccharides (FOS), and inulin-enriched cookie (De Luis et al. 2011). Improvements of glycemic control and lipid profile have been reported after consumption of glucomannan-enriched biscuits in subjects with impaired glucose tolerance, reduced high density lipoprotein (HDL) cholesterol, elevated serum triglycerides, and moderate hypertension (Vuksan et al. 2000) In this pilot study, we aimed to investigate the relationship between the improvement of postprandial dysmetabolism by a functional cookie, covered by dark chocolate and containing glucomannan, inulin, FOS, and Bacillus coagulans strain GanedenBC30 (Jensen et al. 2010), and the PLIR.Delays in processing are frequent because of problems associated with transporting the samples to the laboratory. Thus, we aimed to evaluate the effect of sample storage on the Peroxidation of Leukocytes Index Ratio (PLIR). Differences between PLIR values of lymphocytes (PLIR-L), monocytes (PLIR-M) and granulocytes (PLIR-G) were observed in fresh samples. Sample storage affected the evaluation of PLIR. In particular, PLIR-L was lower in stored samples compared to fresh samples. In conclusion, our results suggest that fresh samples are recommended for assessing the PLIR.In vitro evaluation of Wheat germ extracts on the Peroxidation of Leukocytes Index Ratio (PLIR). For the in vitro study we choose wheat germ due to its high contents of antioxidants (tocopherols carotenoids, flavonoids and phenolic acids) (Fardet 2010, Zielinski & Kozlova, 2000, Nystro et al.2007, Hidalgo et al.2008, Eisenmenger & Dunford 2008). The wheat bran and germ fraction in whole grain wheat flour contributed 83% of total phenolic content, 79% of total flavonoid content, 78% of total zeaxanthin, 51% of total lutein, and 42% of total β-cryptoxanthin (Liu, 2007; Adom et al., 2005). Besides, whole-grain products are protective against weight gain (Kristensen et al. 2011, Mozaffarian et al. 2011), type 2 diabetes(de Munter et al. 2007, Nettleton et al. 2010, Priebe et al. 2008, Schulze et al. 2007, Sun et al. 2010) and CVD (Anderson 2003, Anderson et al. 2000, Mellen et al. 2008). The effect on PLIR of extracts, obtained by pressurized liquid extraction (PLE) and supercritical fluid extraction, were compared with in vitro antioxidant activity indicators

Free Radicals Generated by Post-Prandial Oxidative Burst in the Early Alterations of Vascular Contractility

Repeated high fat and high carbohydrate meals (HFHCM) generate atherosclerosis, isolated systolic hypertension (ISH), autonomic and endothelial dysfunction. Consequently, old people are particularly susceptible to both flowmediated dilation (FMD) impairment and postprandial hypotension. Despite the mounting evidence that free radicals substantially alter blood pressure and endothelial function, the mechanisms that outline these phenomena are unclear. We have reviewed the effects of the free radicals generated by post-prandial oxidative burst on vascular contractility. Postprandial endotoxemia seems to play a crucial role in both oxidative burst and inflammatory response after meal. Oxidative burst produces both reactive oxygen species (ROS) and reactive nitrogen species (RNS). The reviewed results do not support the hypothesis that a sparing NO• effect is the primary cause of the early alteration of vascular contractility induced by oxidative burst. The contrasting results of various ROS seem to be due to the differentiated effect or toxicity to endothelium or vascular smooth muscle, while lypopolisaccaride, peroxinitrite and peroxyl radicals induce hypotension. On the other hand, immune activation improves sympathetic nervous system (SNS) activity and the compensatory adrenergic response to postprandial hypotension has anti-inflammatory activity. Besides, insulin inhibits post-prandial oxidative burst, post-prandial oxidative stress and inflammation activate the xanthine oxidase and induce the antioxidant enzymes. In conclusion, repeated HFHCM meal ingestion could induce hyper-insulinaemia, chronic SNS and antioxidant enzymes activation. These defensive mechanisms, to both post-prandial hypotension and inflammation, generate autonomic dysfunction and FMD impairment, whereas the chronic oxidative stress induces structural changes in the arteries leading to ISH

Effects of peroxyl radicals on contractility of rabbit aorta and guinea pig atria

Background: High-fat meals may lead to hypotension, oxidative stress and increases of lipopolysaccharide (LPS). Contrasting results have been reported after treatment of isolated tissues with hydrogen peroxide and LPS, whereas the effects of peroxyl radicals, involved in the propagation reaction of lipoperoxidation, have not been investigated previously. Aim: In the present study, we aimed to evaluate the effects of peroxyl radicals on the contractile responses in isolated rabbit aorta and guinea pig atria. Methods and Results: We treated isolated guinea pig atria, rabbit aorta strips and rings with 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH). AAPH did not affect isoprenaline-induced contraction in guinea pig atria, whilst it dose-dependently reduced the contractile responses induced in rabbit aorta strips by cumulative doses of adrenaline (ADR) and induced an endothelium-independent relaxation of noradrenaline (NA)-contracted aorta rings. The effects of KCl-induced and BaCl2-induced contractions were small. Furthermore, alkalinization with NH4Cl of NA-contracted aorta rings significantly reduced the vasodilatatory activity of AAPH. Conclusion: The present study suggests that peroxyl radicals induce acute functional alterations on vascular contraction through intracellular pH regulation. This finding could be related to the documented after meal increase in oxidative burst and endotoxin and the related hypotension

Camellia sinensis in asymptomatic hyperuricaemia: a meta-analysis of tea or tea extract effects on uric acid levels

Flavanols of Camellia sinensis exhibit uric acid (UA) lowering effect, through the modulation of both xanthine oxidase and urate excretion. In order to investigate the potential benefit of Camellia Sinenis products in asymptomatic hyperuricaemia, a meta-analysis of long-term Randomized Controlled Trials (RCT) with tea or tea extract has been conducted. From 20 human intervention studies selected only 5 RCT (13 interventions) were suitable for meta-analysis (n=472). The current "normal" range set for hyperuricaemia fails to identify patients with potential metabolic disorders. Therefore on the basis of the literature data, we fixed cut off limits for UA baseline levels of 4.5 mg/dl for women, 6.1 mg/dl for men and 5.5 mg/dl for studies involving mixed populations. tatistically significant effects were not found, but subgroup analysis revealed that the Pooled Estimate effect was different in subjects with baseline levels under [MD (95% CI): 0.1078 (-0.0528 to 0.2684)] and over the cut off [MD (95% CI): -0.0239 (0.3311 to 0.2833)]. However, due to the low number of RCT and to the lack of data on bioavailability, it is difficult to draw any firm conclusion and more studies are needed to establish if tea flavanols could be useful in asymptomatic hyperuricaemia treatment

Effects of red wine on postprandial stress: potential implication in non-alcoholic fatty liver disease development

Red wine consumption is considered to be protective against oxidative stress. Diet strongly influences non-alcoholic fatty liver disease, which is associated with oxidative stress and is considered the hepatic manifestation of the metabolic syndrome. METHODS: We reviewed the available evidence that investigated the effects of red wine on the postprandial-induced metabolic and oxidative stress in humans. RESULTS: After red wine consumption with meal, despite the improvement in non-enzymatic antioxidant capacity and lipoperoxidation markers, the influence of confounding factors such as uric acid should be taken into account. Both uric acid and triglycerides increases, induced by ethanol, could cause liver damage. On the other hand, further researches are required in order to understand the meaning of the induction of antioxidant enzymes by red wine and red wine polyphenols in the context of non-alcoholic fatty liver disease. CONCLUSION: In conclusion, inconsistent and contrasting findings exist regarding the potential benefits of red wine consumption against postprandial stress

Investigating the sulfhydryl redox status in the hypotensive acute effects of peroxyl radicals

Post-prandial hypotension is a well-known phenomenon. We aimed to investigate, in the absence of immune and metabolic interfering factors, the correlation of the plasma antioxidant capacity with the early alterations of blood pressure induced by peroxyl radicals. We previously suggested that the hypotensive effect of acute infusion of peroxyl radical generators in rats could be mediated by sulfhydryl (SH) redox status. Therefore, in this study we evaluated the plasma SH, peroxides (ROOH) and both lipophilic (LAC) and hydrophilic (HAC) antioxidant capacity, before, during and after the hypotension induced by 2,2’-azobis- (2-amidinopropane) dihydrochloride (AAPH) and 2,2’-Azobis 2,4-di-methylvaleronitrile (AMVN). As a result AAPH infusion induced a rapid decrease of HAC and SH, these effects were followed by a strong increase of both markers, whereas AMVN treatment was unable to change the HAC and SH values. On the other hand AMVN reduced plasma LAC and increased ROOH, while, in the animals treated with AAPH, ROOH and LAC were decreased and unchanged, respectively. Therefore, SH redox status seems to be not involved in the hypotensive acute effects of peroxyl radicals. Further studies are needed to better understand the mechanisms responsible for paradoxical effects of acute oxidative stres

Interference of flavonoids with fluorescent intracellular probes: methodological implications in the evaluation of the oxidative burst by flow cytometry

The evaluation of oxidative burst is particularly relevant in many pathological and subclinical conditions. Flow cytometry provides quick and accurate measures of the reactive oxygen species production by leukocytes in most situations. However, spurious results, related to probes' efflux may be observed in several instances. Many factors affect the evaluation of the oxidative burst with fluorescent probes that require intracellular deacetylation and could be substrate of the multidrug resistance proteins (MDR). After discussing the implications of the efflux of fluorophores in the normalization strategies in flow cytometry assays, we have pointed out the possible interference of flavonoids with fluorescet probes' staining and signal. We have also reviewed the results from human intervention studies regarding the evaluation of oxidative burst with these probes. In vitro, at concentrations close to post-ingestion circulating levels, some flavonoids and their metabolites could interfere with probes' staining and fluorescence signal through different mechanisms, such as the inhibition of esterases, the modulation of the MDR-mediate efflux of probe and the inhibition of the oxidation of probe. These effects may explain the contrasting results obtained by human intervention studies. Finally, also inflammatory state or the use of drugs substrate of MDR proteins could affect the evaluation of the oxidative burst with intracellular probes