Consommation alimentaire d’antioxydants et risque de cancer du poumon : une étude cas-témoins montréalaise

Objectif : Examiner l’association entre la consommation alimentaire de caroténoïdes (β-carotène, α-carotène, β-cryptoxanthine, lutéine/zéaxanthine, lycopène) et de vitamine C et le risque de cancer du poumon, selon le sexe, l’intensité de tabagisme et le sous-type histologique de la tumeur. Méthodes : Les données proviennent d’une étude cas-témoins menée à Montréal, Canada. Des entrevues ont été effectuées auprès de 1 105 cas incidents de cancer du poumon et 1 449 témoins issus de la population générale. Leur fréquence de consommation moyenne de 49 fruits et légumes deux ans auparavant a été convertie en apports en antioxydants. Les rapports de cotes (RC) et les intervalles de confiance (IC) à 95% caractérisant l’association entre les antioxydants et le risque de cancer du poumon ont été estimés à l’aide de modèles de régression logistique et polytomée, en tenant compte de facteurs de confusion potentiels. Résultats : Une consommation élevée en antioxydants était généralement associée à une diminution du risque de cancer du poumon de l’ordre de 30%. Un effet protecteur a été observé chez les hommes et les femmes, pour les non fumeurs, les fumeurs quelque soit l’intensité de tabagisme, ainsi que pour les carcinomes à petites cellules, épidermoïde et l’adénocarcinome. Conclusions : Plusieurs antioxydants alimentaires protégeraient du cancer du poumon. Les efforts de prévention bénéficieraient de cibler la promotion de la consommation de fruits et de légumes riches en caroténoïdes et en vitamine C.

Plasma lipid profile of experimentally induced hyperlipidemic New Zealand white rabbits is not affected by resveratrol

Hyperlipidemia is well recognized as an important risk factor in the development of atherosclerosis. Low-density lipoproteins (LDL) are components of cholesterol that are highly associated to an increased risk of cardiovascular diseases. Hypercholesterolemia induces proteolytic and oxidative changes in vasculature, leading to a local inflammatory response. Since dietary antioxidants have attracted considerable attention as preventive and therapeutic agents, the polyphenolic compound resveratrol seems to play an important role in prevention of human atherosclerosis. Researches show that resveratrol inhibits LDL oxidation and platelet aggregation, as well as vascular prolifer ation of smooth muscle cells. However, recent findings in animal models reveal conflicting results regarding its effects on plasma lipid levels. The aim of the present study was to evaluate the effect of resveratrol on plasma biochemistry profile in New Zealand white rabbits submitted to a hypercholesterolemic diet. Twenty healthy, male, adult New Zealand white rabbits were fed with ordinary diet for one week before being divided into four treatment groups, containing five animals each. Group CT received maintenance diet; group R received maintenance diet and resveratrol (3mg/kg/day) given orally; group CL received maintenance diet enriched with 1.5% cholesterol; and group CR received maintenance diet enriched with 1.5% cholesterol and resveratrol (3mg/kg/day) given orally. During the experiment, from each animal, samples of 3mL venous blood were collected in heparin twice monthly for measurements of total cholesterol, triglycerides, and low- and high-density lipoproteins. The data analysis revealed that resveratrol did not have a hypolipidemic effect in experimentally induced hypercholesterolemic New Zealand white rabbits.

Avaliação do estado nutricional, ingestão de antioxidante e extensão da lesão intestinal em pacientes portadores de colte ulcerativa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antioxidant intake among Brazilian adults - The Brazilian Osteoporosis Study (BRAZOS): a cross-sectional study

Abstract Background Antioxidant nutrient intake and the lesser formation of free radicals seem to contribute to chronic diseases. The aim of the present study was to evaluate the intake profile of the main dietary antioxidants in a representative sample of the adult Brazilian population and discuss the main consequences of a low intake of these micronutrients on overall health. Methods The sample comprised 2344 individuals aged 40 years or older from 150 cities and was based on a probabilistic sample from official data. The research was conducted through in-home interviews administered by a team trained for this purpose. Dietary intake information was obtained through 24-h recall. The Nutrition Data System for Research software program was used to analyze data on the intake of vitamins A, C and E, selenium and zinc, which was compared to Dietary Reference Intakes (DRIs). Differences in intake according to sex, anthropometrics, socioeconomic status and region were also evaluated. The SPSS statistical package (version 13) was used for the statistical analysis. P-values < 0.05 were considered significant. Results Higher proportions of low intake in relation to recommended values were found for vitamin E (99.7%), vitamin A (92.4%) and vitamin C (85.1%) in both genders. Intake variations were found between different regions, which may reflect cultural habits. Conclusion These results should lead to the development of public health policies that encourage educational strategies for improving the intake of micronutrients, which are essential to overall health and prevention of non-communicable diseases.

Influência da localização geográfica de produção nas propriedades de mirtilos 'Vaccinium Corymbosum L.' cv Bluecrop

Os antioxidantes na dieta podem ter um papel importante na prevenção de algumas doenças crónicas em seres humanos resultantes da oxidação de lípidos e outros componentes celulares por radicais livres. Os mirtilos (Vaccinium sp.) são considerados, de entre os frutos frescos, uma das melhores fontes de antioxidantes. Neste trabalho foram estudados mirtilos Nothern Highbush, da cultivar Bluecrop colhidos no estado de maturação comercial em 5 localizações diferentes: Bouças -Sever do Vouga, Estarreja, Queirã – Vouzela, Oliveira do Hospital e Vila Verde. Foram avaliadas as características físico-químicas (ºbrix, acidez, humidade, calibre, firmeza, elasticidade e parâmetros colorimétricos) dos frutos. Para a determinação da composição fenólica e a atividade antioxidante os mirtilos foram submetidos a extrações sucessivas, com metanol (2x) e depois 2 vezes com uma solução aquosa de acetona (40% v/v), durante 1 h, com o auxílio de um banho de ultrassons. Os extratos obtidos foram utilizados para a determinação da composição fenólica (compostos fenólicos totais, antocianinas e taninos) e da capacidade antioxidante (utilizando os métodos ABTS, DPPH e FRAP). Foi ainda avaliada a influência da conservação durante 6 meses a -20ºC no teor de compostos fenólicos e capacidade antioxidante dos frutos. Pelos resultados obtidos, nos parâmetros de textura avaliados a amostra BBO revelou maior firmeza e elasticidade, e na avaliação da cor a amostra BES apresentou uma tonalidade azul mais acentuada. Os mirtilos provenientes de Estarreja eram os mais ricos em compostos fenólicos totais, em antocianinas e taninos, e que também apresentavam maior atividade antioxidante. O armazenamento durante 6 meses a -20ºC, originou diferenças significativas nas antocianinas e na atividade antioxidante. Em geral as amostras apresentavam diferenças significativas tanto nas suas propriedades físico-químicas, como na composição fenólica e na atividade antioxidante.

Kidney dysfunction and hypertension: Role for cadmium, P450 and heme oxygenases?

Cadmium (Cd) is a metal toxin of continuing worldwide concern. Daily intake of Cd, albeit in small quantities, is associated with a number of adverse health effects which are attributable to distinct pathological changes in a variety of tissues and organs. In the present review, we focus on its renal tubular effects in people who have been exposed environmentally to Cd at levels below the provisional tolerable intake level set for the toxin. We highlight the data linking such low-level Cd intake with tubular injury, altered abundance of cytochromes P450 (CYPs) in the kidney and an expression of a hypertensive phenotype. We provide updated knowledge on renal and vascular effects of the eicosanoids 20-hydroxyeicosatetraenoic acid (20-HETE) and eicosatrienoic acids (EETs), which are biologically active metabolites from arachidonate metabolism mediated by certain CYPs in the kidney. We note the ability of Cd to elicit oxidative stress and to alter metal homeostasis notably of zinc which may lead to augmentation of the defense mechanisms involving induction of the antioxidant enzyme heme oxygenase-1 (HO-1) and the metal binding protein metallothionein (MT) in the kidney. We hypothesize that renal Cd accumulation triggers the host responses mediated by HO-I and MT in an attempt to protect the kidney against injurious oxidative stress and to resist a rise in blood pressure levels. This hypothesis predicts that individuals with less active HO-1 (caused by the HO-1 genetic polymorphisms) are more likely to have renal injury and express a hypertensive phenotype following chronic ingestion of low-level Cd, compared with those having more active HO-1. Future analytical and molecular epidemiologic research should pave the way to the utility of induction of heme oxygenases together with dietary antioxidants in reducing the risk of kidney injury and hypertension in susceptible people.

Biomarkers

Introduction – Why do we need ‘biomarkers? Biomarkers of protein oxidation Introduction Major issues/questions Protein carbonyl biomarkers Biochemistry Methods of measurement Storage, stability and limitations in use Protein thiol biomarkers Biochemistry Methods of measurement Storage, stability and limitations on use Aliphatic amino acid biomarkers Biochemistry Methods of measurement Storage, stability and limitations on use Oxidised Tryptophan Biomarkers Biochemistry Method of measurement Storage, stability and limitations on use Oxidised tyrosine biomarkers Biochemistry Methods of measurement Storage, stability and limitations on use Formation of neoepitopes on oxidised proteins Validation of assays for protein oxidation biomarkers Relationship of protein oxidation to disease Modulation of protein oxidation biomarkers by antioxidants Future perspectives Introduction to lipid peroxidation biomarkers Introduction: biochemistry of lipid peroxidation Malondialdehyde Methods of measurement Storage, stability and limitations on use Conjugated dienes Method of measurement Storage, stability and limitations of use LDL lag phase Method of measurement Storage, stability and limitations of use Hydrocarbon gases Biochemistry Method of measurement Storage, stability and limitations on use Lipofuscin Biochemistry Method of measurement Storage, stability and limitation on use Lipid peroxides Biochemistry Method of measurement Storage, stability and limitations on use Isoprostanes Biochemistry Method of measurement Storage, stability and limitations on use Possible new biomarkers of lipid oxidation Relationship of lipid peroxidation to disease Modulation of lipid peroxidation biomarkers by antioxidants Functional consequences of lipid peroxidation Contribution of dietary intake to lipid peroxidation products Biomarkers of DNA oxidation Introduction Confounding factors Units and terminology Nuclear and mitochondrial DNA damage Lymphocytes as surrogate tissues Measurement of DNA damage with the comet assay Practical details Storage, stability, and limitations of the assay Measurement of DNA base oxidation by HPLC Practical details Storage, stability and limitations of the method Measurement of DNA base oxidation by GC–MS Biochemistry of 8-oxoguanine, adenine and fapy derivatives Methods of measurement Storage, stability and limitations of the method Analysis of guanine oxidation products in urine Method of measurement Limitations and criticisms Immunochemical methods Methods of measurement Storage, stability, and limitations of the assay 32P post-labelling Method of measurement Limitations and criticisms Validation of assays for DNA oxidation Oxo-dGuo in lymphocyte DNA Urinary measurements DNA–aldehyde adducts Biochemistry Method of measurement Products of reactive nitrogen species Endpoints arising from oxidative DNA damage Mutations Chromosome aberrations Micronuclei Site-specific DNA damage Relationship of DNA oxidation to disease Modulation of DNA oxidation biomarkers by antioxidants Direct and indirect effects of oxidative stress: measures of total oxidant/antioxidant levels Visualisation of cellular oxidants Biochemistry: histochemical detection of ROS Method of measurement Limitations, storage and stability Measurement of hydrogen peroxide Biochemistry Methods of measurement Storage, stability and limitations on use Measurement of the ratio of antioxidant/oxidised antioxidant Biochemistry Method of measurement Storage, stability and limitations on use Total antioxidant capacity Biochemistry Terminology Methods of measurement Storage, stability and limitations on use Validation of assays for direct oxidant and antioxidant biomarkers Relationship of oxidant/antioxidant measurement to disease Modulation of oxidant/antioxidant biomarkers by dietary antioxidants Induction of genes in response to oxidative stress Background Measurement of antioxidant responsive genes and proteins Effects of antioxidant intake on the activity of antioxidant enzymes

Novel repair action of vitamin C upon in vivo oxidative DNA damage

There appears to be a paucity of data examining the effect of dietary antioxidants on levels of oxidative DNA damage in vivo, limiting evidence-based assessment of antioxidant efficacy, mechanisms and recommendation for optimal intake. We have examined levels of 8-oxo-2'-deoxyguanosine (8-oxodG) in mononuclear cell DNA, serum and urine from subjects undergoing supplementation with 500 mg/day vitamin C. Significant decreases in DNA levels of 8-oxodG were seen, correlating strongly with increases in plasma vitamin C concentration. Furthermore we established a timecourse for sequential, significant increases in serum and urinary 8-oxodG levels. These results illustrate, for the first time in humans, the kinetics of 8-oxodG removal and processing in vivo, suggesting a role for vitamin C in the regulation of DNA repair enzymes and thereby demonstrating a non-scavenging antioxidant effect.

Vitamin C supplementation in normal subjects reduces constitutive ICAM-1 expression

Regulation of monocyte adhesion molecule gene expression is via redox sensitive transcription factors. We have investigated whether dietary antioxidant supplementation with vitamin C (250mg/day) can modulate monocyte ICAM-1 expression in healthy male subjects with low plasma vitamin C at baseline. In a randomised, double-blind, crossover study, monocyte ICAM-1 mRNA was analysed using quantitative reverse transcriptase PCR. Protein was determined by flow cytometry (monocytes) and ELISA (plasma). Monocyte numbers were unaltered by supplementation. Subjects with low plasma vitamin C (<50μM) prior to supplementation expressed higher levels of monocyte ICAM-1mRNA, and showed a significant (50%) reduction in ICAM-1mRNA expression after 6 weeks of 250mg/day vitamin C supplementation (p<0.05). This was paralleled by a reduction in sICAM-1 (p<0.05). For the first time, these results show that dietary vitamin C can modulate monocyte ICAM-1 gene expression in vivo, where regulation of gene expression represents a novel mechanism for benefit from dietary antioxidants. © 2003 Elsevier Inc. All rights reserved.

Deoxycytidine glyoxal:Lesion induction and evidence of repair following vitamin C supplementation in vivo

Oxidative DNA damage is postulated to be involved in carcinogenesis, and as a consequence, dietary antioxidants have received much interest. A recent report indicates that vitamin C facilitates the decomposition of hydroperoxides in vitro, generating reactive aldehydes. We present evidence for the in vivo generation of glyoxal, an established product of lipid peroxidation, glucose/ascorbate autoxidation, or free radical attack of deoxyribose, following supplementation of volunteers with 400 mg/d vitamin C. Utilizing a monoclonal antibody to a deoxycytidine-glyoxal adduct (gdC), we measured DNA lesion levels in peripheral blood mononuclear cells. Supplementation resulted in significant (p = .001) increases in gdC levels at weeks 11, 16, and 21, with corresponding increases in plasma malondialdehyde levels and, coupled with previous findings, is strongly suggestive of a pro-oxidative effect. However, continued supplementation revealed a highly significant (p = .0001) reduction in gdC levels. Simultaneous analysis of cyclobutane thymine dimers revealed no increase upon supplementation but, as with gdC, levels decreased. Although no single mechanism is identified, our data demonstrate a pro-oxidant event in the generation of reactive aldehydes following vitamin C supplementation in vivo. These results are also consistent with our hypothesis for a role of vitamin C in an adaptive/repair response and indicate that nucleotide excision repair specifically may be affected. © 2003 Elsevier Science Inc.

The influence of diet on protein oxidation

Protein oxidation can be perceived as essential for the control of intracellular signalling and gene expression on the one hand, but in contrast, a potentially cytotoxic hazard of aerobic life. Reduction and oxidation of thiol groups on specific cysteine residues can act as critical molecular switches, in modulating response to growth factors, apoptotic and inflammatory stimuli to name a few. Such oxidative reactions are likely to be transient and represent low levels of oxidative modification to a protein. Sustained oxidative stress conditions through absence of essential dietary antioxidant or low activity of endogenous enzyme scavengers can cause irreversible damage and loss of function. Such modifications are believed to be important in many diseases associated with ageing. Therefore, it has been postulated that diet may exert an influence on the steady state of protein oxidation and thus offer potential health benefits through preservation of normal protein function. In the present paper, the current evidence from in vivo studies on the effects of dietary antioxidants and oxidants on protein oxidation will be evaluated, and needs for future research will be highlighted.

Plant derived and dietary phenolic antioxidants: Anticancer properties

n this paper, a review of the literature on the phenolic compounds with anticancer activity published between 2008 and 2012 is presented. In this overview only phenolic antioxidant compounds that display significant anticancer activity have been described. In the first part of this review, the oxidative and nitrosative stress relation with cancer are described. In the second part, the plant-derived food extracts, containing identified phenolic antioxidants, the phenolic antioxidants isolated from plants and plant-derived food or commercially available and the synthetic ones, along with the type of cancer and cells where they exert anticancer activity, are described and summarized in tables. The principal mechanisms for their anti-proliferative effects were also described. Finally, a critical analysis of the studies and directions for future research are included in the conclusion.

Dietary n-6- or n-3-rich vegetable fats and antioxidants: effects on fatty acid composition and stability of rabbit plasma, liver and meat

We supplemented diets with a-tocopheryl acetate (100 mg/kg) and replaced beef tallow (BT) in feeds with increasing doses of n-6- or n-3-rich vegetable fat sources (linseed and sunflower oil), and studied the effects on the fatty acid (FA) composition, the a-tocopherol (aT) content and the oxidative stability of rabbit plasma and liver. These effects were compared with those observed in a previous study in rabbit meat. As in meat, the content of saturated, monounsaturated and trans FA in plasma and liver mainly reflected feed FA profile, except stearic acid in liver, which increased as feeds contained higher doses of vegetable fat, which could be related to an inhibition of the activity of the stearoyl-CoA-desaturase. As linseed oil increased in feeds, the n-6/n-3 FA ratio was decreased in plasma and liver as a result of the incorporation of FA from diets and also, due to the different performance and selectivity of desaturase enzymes. However, an increase in the dose of vegetable fat in feeds led to a significant reduction in the aT content of plasma and liver, which was greater when the fat source was linseed oil. Increasing the dose of vegetable fat in feeds also led to an increase in the susceptibility to oxidation (lipid hydroperoxide (LHP) value) of rabbit plasma, liver and meat and on the thiobarbituric acid (TBA) values of meat. Although the dietary supplementation with a-tocopheryl acetate increased the aT content in plasma and liver, it did not modify significantly their TBA or LHP values. In meat however, both TBA and LHP values were reduced by the dietary supplementation with a-tocopheryl acetate. The plasma aT content reflected the aT content in tissues, and correlated negatively with tissue oxidability. From the studied diets, those containing 1.5% linseed oil plus 1.5% BT and 100 mg of a-tocopheryl acetate/kg most improved the FA composition and the oxidative stability of rabbit tissues.

Potential dietary sources of ellagic acid and other antioxidants among fruits consumed in Brazil: Jabuticaba (Myrciaria jaboticaba (Vell.) Berg)

BACKGROUND: The objectives of this study were (1) to evaluate the content of ellagic acid in fruits consumed by the Brazilian population, including native ones; (2) to further characterize rich sources in relation to ascorbic acid, phenolics contents and in vitro antioxidant capacity; and (3) to study the distribution and effect of ripening stage on ellagitannins content of jabuticaba (Myrciaria jaboticaba). The content of free ellagic acid and ellagic acid derivatives such as ellagitannins was analyzed using high-performance liquid chromatography (HPLC). RESULTS: Ellagic acid was detected in 10 out of a total of 35 fruits analyzed. The content of free ellagic acid in fruits varied from 0.0028 to 0.085 g kg(-1) (FW) and total ellagic acid varied from 0.215 to 3.11 g kg(-1) (FW). All the seven fruits belonging to the Myrtaceae family evaluated in this study presented high contents of ellagitannins in their composition, with jabuticaba, grumixama and cambuci (all native from Brazil) showing the highest total ellagic acid contents. Jabuticaba, the most consumed in Brazilamongthose and already adapted to commercial plantations, contained concentrated phenolics compounds, including ellagitannins, in the peel. Anthocyanins (cyanidin derivatives) increased significantly through ripening of jabuticaba and were not present in the pulp or seeds. Samples collected from three different locations during summer, winter and spring had total ellagic contents varying from 1.88 to 3.31 g kg(-1) (FW). The decrease in ellagic acid content with ripening was more accentuated for pulp (eight times) compared to seeds (2.3 times) and peel (2.0 times). CONCLUSION: These results showed the potential of jabuticaba as dietary source of ellagic acid and reinforced consumption of the whole fruit by the population. (C) 2011 Society of Chemical Industry

Effects of natural antioxidants on the lipid profile of electron beam-irradiated beef burgers

The purpose of this study was to assess the efficacy of rosemary and oregano extracts in avoiding oxidative changes in beef burgers, and to evaluate the fatty acid profile of these products after electron beam exposition. Extracts, individually or in combination, were added to beef burgers and compared to synthetic antioxidants commonly used in food (butylated hydroxytoluene, butylated hydroxyanisole). The ground beef were submitted to electron beam irradiation at doses of 0, 3.5 and 7 kGy, and stored for 90 days. At regular time intervals, lipid oxidation and fatty acid composition were evaluated through measurement of thiobarbituric acid-reactive substances (TBARS) and gas chromatography, respectively. The results indicate that, although the irradiation process triggers an increase in the lipid oxidation ratio expressed by TBARS values, great changes in the fatty acid profiles were not observed; instead, they continued to present characteristics very similar to that of non-irradiated beef. Thus, as irradiation doses of up to 7 kGy for frozen meat can make foods safe from foodborne pathogens, natural antioxidants derived from spices are able to reduce and avoid lipid changes that may cause a deterioration of the sensory quality of these foods, and these natural extracts offer a good choice for replacing synthetic additives.