Polyphenol-rich food general and on pregnancy effects: a review.

This review aimed to investigate possible protective or deleterious effects of polyphenol-rich foods (PRF) on chronic diseases, e.g. cardiovascular, and in pregnant women, along with their antioxidant and anti-inflammatory action. A great variety of foods and beverages, such as herbal teas, grape and orange derivatives, dark chocolate, and many others contain high concentrations of flavonoids and are freely consumed by the general population. In humans, PRF consumption reduces lipid peroxidation, and several studies have shown a positive correlation between an increased consumption of PRF and a decrease in the incidence of cardiovascular disease. On the other hand, current studies have suggested that maternal ingestion of PRF, especially during the third trimester of pregnancy, could be associated to fetal ductal constriction (DC). Fetuses exposed to this type of diet show higher ductal velocities and lower pulsatility indexes, as well as larger right ventricles than those exposed to minimal amounts of these substances. The underlying mechanism involved in these conditions has not been entirely elucidated, but it seems to be a result of the antioxidant and anti-inflammatory effects of polyphenols by some pathway. Furthermore, taking into account the deleterious effect in late-pregnancy against the numerous positive effects associated to polyphenols, this dual behavior deserves attention particularly to control the dietary ingestion of PRF during gestation. In this line, same PRF, natural constituents of human diet, may represent risk to fetal in late pregnancy compared to the use of nonsteroidal anti-inflammatory drugs.

Associations among environmental exposure to manganese, neuropsychological performance, oxidative damage and kidney biomarkers in children.

Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6-12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions - inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), δ-aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl2 (ALA-RE/ZnCl2), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-ß-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children (p<0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (ß=0.649; p<0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions - inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers (p<0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks (p<0.05). The findings of this study suggest an important association between environmental exposure to Mn and toxic effects on neuropsychological function, oxidative damage and kidney function in children.

Cognitive deficits and ALA-D-inhibition in children exposed to multiple metals.

Children are especially vulnerable to adverse effects of multiple metals exposure. The aim of this study was to assess some metals concentrations such as lead (Pb), arsenic (As), chromium (Cr), manganese (Mn) and iron (Fe) in whole blood, serum, hair and drinking water samples using inductively coupled plasma-mass spectrometry (ICP-MS) in rural and urban children. In addition, evaluate the adverse effects of multiple metals exposure on cognitive function and δ-aminolevulinate dehydratase (ALA-D) activity. The cognitive ability assessment was performed by the Raven's Colored Progressive Matrices (RCPM) test. The ALA-D activity and ALA-D reactivation index (ALA-RE) activity with DTT and ZnCl2 also were determined. Forty-six rural children and 23 urban children were enrolled in this study. Rural children showed percentile IQ scores in the RCPM test significantly decreased in relation to urban children. According to multiple linear regression analysis, the Mn and Fe in hair may account for the cognitive deficits of children. Manganese and Fe in hair also were positively correlated with Mn and Fe in drinking water, respectively. These results suggest that drinking water is possibly a source of metals exposure in children. ALA-D activity was decreased and ALA-RE with DTT and ZnCl2 was increased in rural children in comparison to urban children. Moreover, ALA-D inhibition was correlated with Cr blood levels and ALA-RE/DDT and ALA-RE/ZnCl2 were correlated with levels of Cr and Hg in blood. Thus, our results indicated some adverse effects of children's exposure to multiple metals, such as cognitive deficits and ALA-D inhibition, mainly associated to Mn, Fe, Cr and Hg.

Nitric oxide and reactive species are modulated in the polyphenol-induced ductus arteriosus constriction in pregnant sheep.

OBJECTIVE: Because we have previously demonstrated the relation between polyphenol-rich foods (PRF) consumption and ductus arteriosus constriction, in this work, pregnant sheep were submitted to oral PRF intake for 14 days to understand how this process occurs. Fetal Doppler echocardiography, oxidative and inflammatory biomarkers and total polyphenol excretion were evaluated. RESULTS: The high polyphenol intake induced ductus arteriosus constriction by 71.6% increase in systolic (P = 0.001) and 57.8% in diastolic velocities (P = 0.002), and 18.9% decrease in pulsatility index (P = 0.033), along with 1.7-fold increase in total polyphenol excretion, 2.3-fold decrease in inflammatory mediator nitric oxide and following redox status changes (mean ± standard deviation): higher protein carbonyls (1.09 ± 0.09 and 1.49 ± 0.31), catalase (0.69 ± 0.39 and 1.44 ± 0.33) and glutathione peroxidase (37.23 ± 11.19 and 62.96 ± 15.03) in addition to lower lipid damage (17.22 ± 2.05 and 12.53 ± 2.11) and nonprotein thiols (0.11 ± 0.04 and 0.04 ± 0.01) found before and after treatment, respectively. Ductal parameters correlated to NOx , catalase, glutathione peroxidase and protein carbonyl. CONCLUSION: Our results highlight the need to reduce maternal PRF intake in late pregnancy to prevent fetal duct constriction through NO-mediated vasoconstrictive action of polyphenols.

Exogenous and endogenous antioxidants attenuate the lipid peroxidation in workers occupationally exposed to paints.

Occupational exposure to organic solvents present in paints is responsible for an increased production of reactive species, thus enabling the development of several diseases. Besides, both exo- and endogenous antioxidant defense systems are necessary to avoid oxidative tissue damage. This study investigated possible protective effects of the exo- and endogenous antioxidants on oxidative damage in painters occupationally exposed to organic solvents (n = 42) and controls (n = 28). Retinol, lycopene and ß-carotene were significantly lower in the exposed group. Despite the fact that blood toluene was below the biological exposure limits, malondialdehyde levels and antioxidant enzyme activities were increased, whereas reduced glutathione levels were decreased in painters, compared to nonexposed subjects. Moreover, multivariate regression models showed that reduced glutathione and carotenoids (mainly ß-carotene) have the major influence on lipid peroxidation (LPO). The present work suggests that the exogenous antioxidants, such as carotenoids, could protect occupationally exposed subjects to xenobiotics from LPO.

Genotoxicity and oxidative stress in gasoline station attendants.

We evaluated genotoxic effects of exposure to low levels of benzene, a class I human carcinogen, among gasoline station attendants (GSA). Oxidative stress and the protective effects of antioxidants on DNA damage were also analyzed. Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, the GSA group presented higher DNA damage indices and micronucleus frequencies, increased oxidative protein damage, and decreased antioxidant capacity relative to the control group. Duration of benzene exposure was correlated with DNA and protein damage. The biomarkers evaluated in this work may provide early signals of damage in subjects occupationally exposed to benzene.

Evaluation of genotoxicity and oxidative damage in painters exposed to low levels of toluene.

Toluene is an organic solvent used in numerous processes and products, including industrial paints. Toluene neurotoxicity and reproductive toxicity are well recognized; however, its genotoxicity is still under discussion, and toluene is not classified as a carcinogenic solvent. Using the comet assay and the micronucleus test for detection of possible genotoxic effects of toluene, we monitored industrial painters from Rio Grande do Sul, Brazil. The putative involvement of oxidative stress in genetic damage and the influences of age, smoking, alcohol consumption, and exposure time were also assessed. Although all biomarkers of toluene exposure were below the biological exposure limits, painters presented significantly higher DNA damage (comet assay) than the control group; however, in the micronucleus assay, no significant difference was observed. Painters also showed alterations in hepatic enzymes and albumin levels, as well as oxidative damage, suggesting the involvement of oxidative stress. According to multiple linear regression analysis, blood toluene levels may account for the increased DNA damage in painters. In summary, this study showed that low levels of toluene exposure can cause genetic damage, and this is related to oxidative stress, age, and time of exposure.

DNA damage in the elderly is associated with 5-MTHF levels: a pro-oxidant activity.

The aging phenomenon is associated with oxidative stress damage in biomolecules, especially DNA. 5-Methyltetrahydrofolate (5-MTHF), the active folate form, plays a pivotal role in maintaining genomic integrity. However, recently it was associated with cancer development. In Brazil, there are folic acid enriched foods, such as flour, making the general population chronically exposed to folates. Therefore, the aim of this study was to investigate whether erythrocytes 5-MTHF levels were associated with age-related DNA damage in two groups (elderly and young subjects). Additionally, a study in Caenorhabditis elegans, an in vivo alternative model, was performed to verify if 5-MTHF presents a pro-oxidant effect. A total of 50 elderly and 25 young subjects participated in this study, which analyzed whole blood DNA damage, plasma carbonyl proteins (PCO), and erythrocytes 5-MTHF levels. In addition, ROS and RNS production, survival rate, and lifespan were performed in C. elegans exposed to 5-MTHF. Blood 5-MTHF levels and DNA damage were increased in the elderly compared to the young group. A positive association was found between 5-MTHF levels and DNA damage, and between DNA damage and PCO levels, suggesting an oxidative cause of damage associated with the active folate form. In an experimental study it was observed that 5-MTHF increased ROS production in C. elegans, in a dose dependent manner, while survival rate and life span were not affected at the test doses. These findings suggest that 5-MTHF, the active folate form, may be involved in DNA damage in the elderly. This damage could be a result of oxidative stress, as observed in the in vivo alternative model; however, more studies are necessary to prove our present results.

Biomonitoring of gasoline station attendants exposed to benzene: Effect of gender.

Women are employed in increasing numbers as gasoline station attendants, a work category with risk of exposure to benzene. We have assessed the effect of gender on biomarkers of occupational benzene exposure. Gasoline station attendants (20 men and 20 women) and 40 control individuals (20 men and 20 women) with no history of occupational benzene exposure were evaluated. Benzene exposure was monitoring by environmental and biological measurements. Urinary trans,trans-muconic acid levels, well-known genetic and hematological alterations linked to benzene exposure, and non-cancer effects on the immune, hepatic, and renal systems were investigated. Our results suggest a potential effect of gender on some effects of occupational benzene exposure, particularly the hematological parameters and trans,trans-muconic acid levels. Despite limitations of our study, our findings provide important considerations about occupational exposure of women to benzene and may contribute to the development of occupational protection standards.

Environmental exposure and effects on health of children from a tobacco-producing region.

Children may be environmentally exposed to several hazards. In order to evaluate the health of children living in a tobacco-producing region, different biomarkers of exposure and effect, as well as hematological parameters, were evaluated. Biomarkers of exposure to the following xenobiotics were assessed: pesticides, nicotine, toxic elements, and organic solvents. Oxidative damage markers malondialdehyde (MDA) and protein carbonyls (PCO), vitamin C, microalbuminuria (mALB) levels, and N-acetyl-ß-D-glucosaminidase (NAG) activity were also evaluated. Peripheral blood samples and urine were collected from 40 children (6-12 years), at two different crop periods: in the beginning of pesticide applications (period 1) and in the leaf harvest (period 2). The Wilcoxon signed-rank test for paired data was used to evaluate the differences between both periods. Biomarkers of exposure cotinine in urine and blood chromium (Cr) levels were increased in period 1 when compared to period 2. Moreover, a significant reduced plasmatic activity of butyrylcholinesterase (BuChE) was observed in period 2 in relation to period 1. Blood Cr levels were above the recommended by WHO in both evaluations. The biomarkers MDA and PCO as well as the kidney dysfunction biomarker, mALB, presented levels significantly increased in period 1. Additionally, decreased lymphocytes and increased basophils were also observed. Cotinine was positively associated with PCO, and Cr was positively associated with PCO and MDA. The increased Cr levels were associated with decreased lymphocytes and increased basophils. Our findings demonstrate that children environmentally exposed to xenobiotics in rural area may present early kidney dysfunction, hematological alterations, as well as lipid and protein damages, associated with co-exposure to different xenobiotics involved in tobacco cultivation.

Evaluation of potential acute cardiotoxicity of biodegradable nanocapsules in rats by intravenous administration.

Nanotoxicology aims to study the safety of nanomaterials, especially towards human exposure. Biodegradable polymeric nanocapsules have been indicated as potential drug carriers applicable for treating several pathologies. Thus, the objective of this study was to evaluate the potential cardiotoxicity of biodegradable lipid-core nanocapsules (LNC) containing poly(ε-caprolactone). Nanocapsules were characterized and the acute toxicity evaluation was conducted in Wistar rats. Two control groups (saline and tween/glycerol) were utilized, and three treated groups were chosen for low, intermediate and high doses: 28.7 × 1012 (LNC-1), 57.5 × 1012 (LNC-2) and 115 × 1012 (LNC-3), expressed as number of nanocapsules per milliliter per kg. Blood pressure measurements were performed in non-anesthetized animals by caudal plethysmography. The electrocardiographic (ECG) and echocardiographic analyses were carried out after anesthesia by isoflurane at two points, prior to treatment and after 14 days. Blood was collected 24 hours and 14 days after treatment. Biochemical and histopathological analyses were performed. During the evaluation period, no deaths, weight loss or clinical signs were observed. Post-treatment systolic pressures (24 h and 14 days) were significantly increased in comparison to pre-treatment in both control groups and treated groups, which is suggested to be as a possible consequence of the infused volume. Serum sodium, potassium, aspartate aminotransferase and alkaline phosphatase, as well as, hematological parameters were within reference values established for rats. ECG showed no indications of cardiotoxicity. Despite the echocardiograms, no alterations in the ejection fraction were found as indicators of cardiotoxicity. Cardiac histopathology also demonstrated no alterations. Therefore, the present results on acute evaluation after i.v. administration, by slow infusion, showed potential safety since no cardiotoxic effects by ECG, echocardiographic, arterial pressure, biochemical and histopathological analyses were found.

Relationship between inflammation and oxidative stress and cognitive decline in the institutionalized elderly.

OBJECTIVE: Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions. METHODS: The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated. RESULTS: The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. CONCLUSIONS: The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy.

Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line.

Many acute poisonings lack effective and specific antidotes. Due to both intentional and accidental exposures, paraquat (PQ) causes thousands of deaths annually, especially by pulmonary fibrosis. Melatonin (Mel), when incorporated into lipid-core nanocapsules (Mel-LNC), has enhanced antioxidant properties. The effects of such a formulation have not yet been studied with respect to mitigation of PQ- induced cytotoxicity and DNA damage. Here, we have tested whether Mel-LNC can ameliorate PQ-induced toxicity in the A549 alveolar epithelial cell line. Physicochemical characterization of the formulations was performed. Cellular uptake was measured using nanocapsules marked with rhodamine B. Cell viability was determined by the MTT assay and DNA damage was assessed by the comet assay. The enzyme-modified comet assay with endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) were used to investigate oxidative DNA damage. Incubation with culture medium for 24h did not alter the granulometric profile of Mel-LNC formulations. Following treatment (3 and 24h), red fluorescence was detected around the cell nucleus, indicating internalization of the formulation. Melatonin solution (Mel), Mel-LNC, and LNC did not have significant effects on cell viability or DNA damage. Pre-treatment with Mel-LNC enhanced cell viability and showed a remarkable reduction in % DNA in tail compared to the PQ group; this was not observed in cells pre-treated with Mel. PQ induces oxidative DNA damage detected with the enzyme-modified comet assay. Mel-LNC reduced this damage more effectively than did Mel. In summary, Mel-LNC is better than Mel at protecting A549 cells from the cytotoxic and genotoxic effects of PQ.

Evaluation of toxic metals and essential elements in children with learning disabilities from a rural area of southern Brazil.

Children's exposure to metals can result in adverse effects such as cognitive function impairments. This study aimed to evaluate some toxic metals and levels of essential trace elements in blood, hair, and drinking water in children from a rural area of Southern Brazil. Cognitive ability and δ-aminolevulinate dehydratase (ALA-D) activity were evaluated. Oxidative stress was evaluated as a main mechanism of metal toxicity, through the quantification of malondialdehyde (MDA) levels. This study included 20 children from a rural area and 20 children from an urban area. Our findings demonstrated increase in blood lead (Pb) levels (BLLs). Also, increased levels of nickel (Ni) in blood and increase of aluminum (Al) levels in hair and drinking water in rural children were found. Deficiency in selenium (Se) levels was observed in rural children as well. Rural children with visual-motor immaturity presented Pb levels in hair significantly increased in relation to rural children without visual-motor immaturity (p < 0.05). Negative correlations between BLLs and ALA-D activity and positive correlations between BLLs and ALA-RE activity were observed. MDA was significantly higher in rural compared to urban children (p < 0.05). Our findings suggest that rural children were co-exposed to toxic metals, especially Al, Pb and Ni. Moreover, a slight deficiency of Se was observed. Low performance on cognitive ability tests and ALA-D inhibition can be related to metal exposure in rural children. Oxidative stress was suggested as a main toxicological mechanism involved in metal exposure.

Evaluation of genotoxicity in workers exposed to benzene and atmospheric pollutants.

Gas station attendants and taxi drivers are occupationally exposed to xenobiotics which may be harmful to their health. Atmospheric pollutants and benzene can lead to DNA damage. Genotoxicity and mutagenicity assays can be used to evaluate the effects of these pollutants. We have evaluated genotoxicity and mutagenicity in workers occupationally exposed to xenobiotics, by application of the 8-hydroxy-2-deoxyguanosine (8-OHdG), comet, and micronucleus (MN) assays. Biomarkers of benzene and carbon monoxyde exposure were also measured: urinary t,t-muconic acid (t,t-MA) and carboxyhaemoglobin (COHb) in whole blood, respectively. The study groups comprised 43 gas station attendants (GSA), 34 taxi drivers (TD), and 22 persons without known occupational exposures (NE). Levels of t,t-MA in the GSA group were significantly elevated compared to the NE group (p<0.001), however these levels were below of levels established by ACGIH (American Conference of Governmental Industrial Hygienists). COHb levels were not significantly different between the TD and NE groups (p>0.05). DNA damage index (DI) and 8-OHdG levels were significantly higher for both the GSA and TD groups, compared to the NE group (p<0.001), but MN frequencies were not elevated. Spearman correlation analysis showed that the frequency of MN was positively correlated with 8-OHdG. A positive correlation between DNA DI levels and 8-OHdG was also observed. In conclusion, our results indicated that low levels of occupational exposure to benzene and atmospheric pollutants may be linked to genotoxicity and oxidative DNA damage.

Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation.

Fatty acid status and its relationship to cognitive decline and homocysteine levels in the elderly.

Polyunsaturated fatty acids (PUFAs), especially the n-3 series, are known for their protective effects. Considering that cardiovascular diseases are risk factors for dementia, which is common at aging, the aim of this study was to evaluate whether fatty acid status in the elderly was associated with cognitive function and cardiovascular risk. Forty-five elderly persons (age ≥ 60 years) were included and divided into two groups based on their Mini-Mental Status Examination score adjusted for educational level: the case group (n = 12) and the control group (n = 33). Serum fatty acid composition, homocysteine (Hcy), hs-CRP, lipid profile and different cognitive domains were evaluated. The case group, characterized by reduced cognitive performance, showed higher levels of 14:0, 16:0, 16:1n-7 fatty acids and lower levels of 22:0, 24:1n-9, 22:6n-3 (DHA) and total PUFAs compared to the control group (p < 0.05). The n-6/n-3 ratio was elevated in both study groups, whereas alterations in Hcy, hs-CRP and lipid profile were observed in the case group. Cognitive function was positively associated with the 24:1n-9, DHA and total n-3 PUFAs, while 14:0, 16:0 and 16:1n-7 fatty acids, the n-6/n-3 ratio and Hcy were inversely associated. In addition, n-3 PUFAs, particularly DHA, were inversely associated with cardiovascular risk, assessed by Hcy levels in the elderly.

Urinary 1-hydroxypyrene is associated with oxidative stress and inflammatory biomarkers in acute Myocardial Infarction.

Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs), with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP) is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI). After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants) and the inflammatory biomarker (hs-CRP) were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05) and were correlated to MDA (r = 0.426, p < 0.01), CAT (r = 0.474, p < 0.001) and ß-carotene (r = -0.309; p < 0.05) in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, ß-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction.

In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration.

Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245±10nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n=6/group) received a single-dose of saline solution (1.2ml/kg) or LNC (7.2×10(12)LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4×10(12)LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p<0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p<0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.

Biomarkers of occupational exposure to air pollution, inflammation and oxidative damage in taxi drivers.

Exposure to environmental pollutants has been recognised as a risk factor for cardiovascular events. 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs) from traffic-related air pollution. Experimental studies indicate that PAH exposure could be associated with inflammation and atherogenesis. Thus, the purpose of this study was to evaluate whether the biomarker of PAH exposure is associated with biomarkers of inflammation and oxidative stress and if these effects modulate the risk of developing cardiovascular diseases in workers exposed to air pollution. This study included 60 subjects, comprising 39 taxi drivers and 21 non-occupationally exposed persons. Environmental PM2.5 and benzo[a]pyrene (BaP) levels, in addition to biomarkers of exposure and oxidative damage, were determined. Inflammatory cytokines (IL-1ß, IL-6, IL-10, TNF-α, IFN-γ and hs-CRP) and serum levels of oxidised LDL (ox-LDL), auto-antibodies (ox-LDL-Ab) and homocysteine (Hcy) were also evaluated. PM2.5 and BaP exhibited averages of 12.4±6.9 µg m(-3) and 1.0±0.6 ng m(-3), respectively. Urinary 1-OHP levels were increased in taxi drivers compared to the non-occupationally exposed subjects (p<0.05) and were positively correlated with pro-inflammatory cytokines and negatively correlated with antioxidants. Furthermore, taxi drivers had elevated pro-inflammatory cytokines, biomarkers of oxidative damage, and ox-LDL, ox-LDL-Ab and Hcy levels, although antioxidant enzymes were decreased compared to the non-occupationally exposed subjects (p<0.05). In summary, our findings indicate that taxi drivers showed major exposure to pollutants, such as PAHs, in relation to non-occupationally exposed subjects. This finding was associated with higher inflammatory biomarkers and Hcy, which represent important predictors for cardiovascular events. These data suggest a contribution of PAHs to cardiovascular diseases upon occupational exposure.