Grape Seed Components as Protectors of Inflammation, DNA Damage, and Cancer.

PURPOSE OF REVIEW: Oxidative stress is related to the pathogenesis of several chronic diseases, including inflammatory processes. Free radicals excess increase not only oxidative stress but also genomic instability. Polyphenols are non-enzymatic antioxidants that act as a defense barrier against free radicals and non-radical oxidants. The purpose of this article was to review published articles relating dietary polyphenols contained in grape seed proanthocyanidin extracts with its potential for reversing DNA damage. RECENT FINDINGS: Proanthocyanidin components exert pleiotropic actions having several biological, biochemical, and significant pharmacological effects and showed the ability to reduce cytotoxicity and genotoxicity. Grape seed proanthocyanidin extracts showed the ability to reduce cytotoxicity and genotoxicity through the comet assay and the micronucleus technique.

Pesticide exposure among students and their families in Nova Friburgo, Rio de Janeiro.

Farming is a risky occupation, especially family farming in developing country. The occupational hazards commonly used in such activity could affect all family members, including children and adolescents. This study describes the pattern of pesticide exposure among students and their families from a farming region located in Nova Friburgo, State of Rio de Janeiro, Brazil. Sociodemographic characteristics, habits, working practices and the degree of exposure to pesticides were assessed by a questionnaire. Our study population consisted of students and family members of both sexes, aged between 6 and 85 years old (N = 352) being 167 women and 185 men. There was a predominance of participants between 10-19 years (71.3%), singles (77.5%), and most had not completed primary education (54.5%). In terms of occupation, 45.5% reported to be farmers and 39.6% were students. The variables mostly associated with pesticide exposure were sex (p < 0.001), educational level (p < 0.001), and being a farmer (p < 0.001). Our results showed that children and teenagers seemed to have the same degree of exposure to pesticides as the adults. Our findings also suggest that sex, occupation and educational level, despite teachers were included, are directly associated with degree of exposure.

Monomeric and oligomeric flavanols maintain the endogenous glucocorticoid response in human macrophages in pro-oxidant conditions in vitro.

Chronic inflammation and oxidative stress are (sub)cellular processes that enhance each other and contribute to the genesis of many systemic pathologies. The endogenous glucocorticoid cortisol plays an important role in the physiological termination of a pro-inflammatory immune response. However, in conditions of pronounced oxidative stress the anti-inflammatory action of cortisol is impaired. Since grape seed-derived monomeric and oligomeric flavan-3-ols (MOF) have been shown to attenuate both inflammation and oxidative stress in vitro and in humans, we hypothesized that these compounds are able to maintain the anti-inflammatory activity of cortisol in immune cells in a pro-oxidant environment. In a glucocorticoid resistance model using human monocytes (THP-1 cell line) differentiated into macrophage-like cells we observed that exposure to 1 mM tertiary butyl hydroperoxide (t-BuOOH) for 4 h significantly hampered the anti-inflammatory action of cortisol assessed as attenuation of the interleukin (IL)-8 production. Under these conditions, the effects of MOF were assessed on pro-inflammatory cytokines expression, cortisol's anti-inflammatory action and on the expression of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) 1, which catalyzes intracellular conversion of cortisone to cortisol. MOF attenuated the gene expression of pro-inflammatory cytokines and prevented the decline of the anti-inflammatory effect of cortisol in the presence of t-BuOOH. MOF also maintained the activity of histone deacetylase in the cell nucleus which is essential for cortisol's molecular action to terminate the transcription of pro-inflammatory genes. Moreover, MOF prevented the down-regulation of 11ß-HSD1 gene expression in this pro-oxidant cellular environment. Taken together our data suggest that MOF contribute to maintain the anti-inflammatory action of cortisol under pro-oxidant conditions via preservation of the intracellular availability of bioactive cortisol and cortisol-mediated termination of pro-inflammatory gene transcription. These findings provide novel insights in how MOF may enhance the ability to adapt, which is of particular relevance for their rational use as dietary supplement to maintain health.

Pesticide exposure among students and their families in Nova Friburgo, Rio de Janeiro / Exposição a agrotóxicos entre estudantes e seus familiares em Nova Friburgo, Rio de Janeiro

Abstract Farming is a risky occupation, especially family farming in developing country. The occupational hazards commonly used in such activity could affect all family members, including children and adolescents. This study describes the pattern of pesticide exposure among students and their families from a farming region located in Nova Friburgo, State of Rio de Janeiro, Brazil. Sociodemographic characteristics, habits, working practices and the degree of exposure to pesticides were assessed by a questionnaire. Our study population consisted of students and family members of both sexes, aged between 6 and 85 years old (N = 352) being 167 women and 185 men. There was a predominance of participants between 10-19 years (71.3%), singles (77.5%), and most had not completed primary education (54.5%). In terms of occupation, 45.5% reported to be farmers and 39.6% were students. The variables mostly associated with pesticide exposure were sex (p < 0.001), educational level (p < 0.001), and being a farmer (p < 0.001). Our results showed that children and teenagers seemed to have the same degree of exposure to pesticides as the adults. Our findings also suggest that sex, occupation and educational level, despite teachers were included, are directly associated with degree of exposure.

Resumo Agricultura é uma ocupação de risco, principalmente a familiar em países em desenvolvimento. Os perigos ocupacionais comuns a essa atividade podem atingir a toda família, incluindo crianças e adolescentes. Este estudo descreve o padrão do uso de agrotóxicos entre estudantes e seus familiares em uma região agrícola localizada em Nova Friburgo, Estado do Rio de Janeiro, Brasil. Características sociodemográficas, hábitos, práticas de trabalho e grau de exposição a agrotóxicos foram adquiridas através do uso de questionário. Nossa população de estudo consistiu em estudantes e seus familiares de ambos os sexos, entre 6 e 85 anos de idade (N = 352) sendo 167 mulheres e 185 homens. Houve a predominância de participantes entre 10 - 19 anos (71,3%), solteiros (77,5%), e a maioria com o ensino fundamental incompleto (54,5%). Quanto à ocupação, 45,5% reportaram-se como agricultores e 39,6% como estudantes. As variáveis mais associadas à exposição a agrotóxicos foram sexo (p < 0,001), nível educacional (p < 0,001) e ser agricultor (p < 0,001). Nossos resultados mostraram que crianças e adolescentes parecem ter o mesmo grau de exposição a agrotóxicos que adultos. Nossos achados também sugerem que sexo, ocupação e nível educacional, incluindo professores, estão diretamente associados ao grau de exposição.

Paraquat disrupts the anti-inflammatory action of cortisol in human macrophages in vitro: therapeutic implications for paraquat intoxications.

The herbicide paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride) has been banned in Europe since 2007 due to its high toxicity in humans. However, it is still widely used in Middle/South America and in Asia where it is annually associated with a high incidence of unintentional and intentional poisoning. Human macrophage-like cell lines were used to shed more light on the inflammatory response elicited by paraquat. Paraquat (3-1000 µM) reduced cell viability in a dose- and time-dependent manner. Exposure to 50 or 200 µM paraquat for 24 h elevated the release of interleukin 8 and gene expression of tumor necrosis factor-α. Expression of the 11ß-hydroxysteroid dehydrogenase 1 gene tended to increase, while cellular glutathione concentrations decreased. The anti-inflammatory effect of cortisol was significantly disrupted. The paraquat-induced cortisol resistance could not be prevented by N-acetyl-l-cysteine. However, a polyphenolic extract of grape seeds consisting of monomeric and oligomeric flavan-3-ols (MOF) reduced paraquat-induced inflammation in the presence of cortisol to baseline. In conclusion, the results suggest that an impaired cortisol response may contribute to paraquat-mediated inflammation. Agents with pleiotropic cellular and subcellular effects on redox regulation and inflammation, such as plant-derived polyphenols, may be an effective add-on to the therapy of paraquat intoxications with glucocorticoids.

Mortalidade de mineiros brasileiros por câncer entre 1979-2005 / Cancer mortality among Brazilian miners during 1979-2005

Os mineiros estão expostos ocupacionalmente a muitos fatores de risco como as poeiras, gases tóxicos, falta de oxigênio, altas temperaturas, metais e radioatividade. A mineração contribui com cerca de 5% do produto interno bruto (PIB) brasileiro e mais de 70% de todas as minas estão localizadas entre as Regiões Sul e Sudeste. O objetivo deste estudo foi avaliar a mortalidade da população mineradora brasileira e das regiões Sul e Sudeste por todas as neoplasias e especificamente pelos cânceres de pulmão/brônquio/traqueia e estômago entre 1979-2005, comparando com a população geral do país e das regiões selecionadas. Os dados de morte foram obtidos através do Sistema de Informação sobre Mortalidade (SIM), de acordo com a CID-9 e CID-10. Em seguida, foi calculada a razão de chance de mortalidade (Mortality Odds Ratio - MOR), estratificada por idade (<60 e >60 anos) e por períodos de morte (1979-1987; 1988-1996; 1997-2005). Os mineradores brasileiros apresentaram um risco de morte elevado para as causas selecionadas e as maiores magnitudes foram encontradas entre os trabalhadores mais jovens. Além disso, houve tendências de aumento do risco ao longo dos três períodos estudados entre os grupos de mineiros de todas as idades (20+ anos). Mineiros das regiões Sul e Sudeste exibiram uma elevação no risco de morte por alguns cânceres, principalmente entre os mais jovens. Na região Sudeste, a população de mineiros chegou a apresentar um risco duas vezes maior de morte por câncer de estômago quando comparada aos trabalhadores não mineiros. Nossos resultados sugerem que mineiros brasileiros apresentam risco elevado de morte por câncer.

Miners are exposed to many risk factors related to their working environment, such as dusts, noxious gases, lack of oxygen, high temperature, metals, and radioactivity. Mining contributes with about 5% to the Brazilian Gross Domestic Product and more than 70% of all mines are located in the South and Southeast regions of the country. The aim of this study was to evaluate the mortality, by any neoplasms and specifically by lung/bronchial/tracheal and stomach cancers, among miners from Brazil, and from the South and Southeast regions between 1979-2005 and comparing it with that experienced by the general population of the country or the said regions. The data of the deaths of miners was obtained through Brazilian Mortality Information System (Sistema de Informação sobre Mortalidade - SIM) according to ICD-9 and ICD-10 from all the country and from the South and Southeast Brazilian regions. Then, the Mortality Odds Ratio (MOR) was calculated, stratified by age (<60 and 60+ years old) and periods of death (1979-1987; 1988-1996; 1997-2005). Brazilian miners showed an increased risk of dying from the herein studied causes, and the highest magnitudes were found among younger workers. Moreover, there were trends of increased risk throughout the three studied periods among the groups of miners of all ages (20+ years old). Miners from South and Southeast regions showed an increased risk of death from some cancers, especially among the younger ones. In the Southeast region, the miners' population showed double the risk of death from stomach cancer when compared to the reference population. Our results suggest that Brazilian miners are at increased risk to die from cancer.

Pesticide exposure and low birth weight prevalence in Brazil.

INTRODUCTION: Brazil is one of the major global consumers of pesticides and exposure to these substances can affect fetal growth. OBJECTIVE: To estimate the correlation between pesticide sales in 1996 and the prevalence of low birth weight during the period 1996-1998 in Brazil. METHOD: This ecological study employed secondary data aggregated at the level of Brazilian micro-regions (cluster of cities). Prevalence of low birth weight in 1996, 1997, and 1998 was obtained from the Brazilian health databases, and per capita pesticides sales in 1996 obtained from the Brazilian Institute of Geography and Statistics were utilized as an indirect measure of population exposure to these chemicals. Spearman correlation coefficient and Prevalence Ratio by quartiles were estimated, considering per capita pesticide sales and the prevalence of low birth weight. RESULTS: A total of 552 micro-regions were analyzed (446 non-urban and 106 urban). In rural areas, the per capita pesticide sales were directly associated with higher prevalence of children born with low birth weight (r=0.403), with birth weights between 1500 and 2500 grams (r=0.366), and very low birth weight birth (r=0.476). All correlations were statistically significant (p<0.001). On the other hand, in urban areas there was no significant correlation. There was a gradual increase in the prevalence of low birth weight according to the quartiles of pesticide consumption. CONCLUSIONS: Pesticide per capita sales may affect the prevalence of newborns with low birth weight in non-urban micro-regions of Brazil, indicating the need to strengthen policies and actions to protect the health of populations exposed to pesticides.