Occupational risk assessment of exposure to metals in chrome plating workers.

Inhalation of xenobiotics during manufacture process in chrome plating bath produce hazards to workers' health. Chromium (Cr) is a metal widely used by industry, and its hexavalent (VI) form has been classified as mutagenic and carcinogenic. This study aimed to evaluate the occupational risk of exposure to metals in chrome plating workers. Biological monitoring was performed through quantification of Cr, Pb, As, Ni, and V in blood by ICP-MS in 50 male chrome-plating workers from the exposed group and 50 male non-exposed workers. The inflammatory parameters assessed were ß-2 integrin, intercellular adhesion molecule-1 (ICAM-1), and L-selectin expression in lymphocytes. The genotoxicity was evaluated with comet and micronucleus (MN) assays and as a biomarker of oxidative damage the lipid peroxidation (MDA) and protein carbonyl (PCO). The results demonstrated that Cr levels in blood and urine were increased in the exposed group compared to the non-exposed group. Although the biomarkers of exposure proved to be within the levels considered safe in exposed individuals, chrome plating workers presented significantly increase in the percentage of lymphocytes expressing ß-2 integrin, ICAM-1, and L-selectin as well as DNA damage (comet assay) and plasmatic MDA and PCO levels. Therefore, it is possible also assign the injuries caused to lipids, proteins, and DNA assessed due to the increased presence of other metals such as Pb, As, Ni, and V in exposed subjects. These results suggest that exposure to xenobiotics present in the occupational environment in chrome plating industry could play a crucial role toward the inflammation, genetic, and oxidative damage.

Children Environmentally Exposed to Agrochemicals in Rural Areas Present Changes in Oxidative Status and DNA Damage.

Rural children are exposed to several chemicals. This study evaluated the environmental co-exposure of rural children to cholinesterase inhibitor insecticides and metals/metalloids, and the resulting oxidative stress and DNA damage. Seventy-two children (5 to 16 years old) were studied at two different moments: period 1, when agrochemicals were less used, and period 2, when agrochemicals were extensively used in agriculture. Biomonitoring was performed by evaluating butyrylcholinesterase (BuChE) activity in serum; arsenic (As), chromium (Cr), lead (Pb), and nickel (Ni) levels in blood; malondialdehyde (MDA) in plasma; glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) activities in whole blood; non-protein thiol levels in erythrocytes; and micronuclei (MN) assay in exfoliated buccal cells. Cr and As levels were higher than the reference values in both periods, and Ni levels were higher than the reference values in period 2 alone. BuChE activity was inhibited in period 2 compared with period 1. In period 2, there was an increase in endogenous antioxidants and a decrease in MDA, probably demonstrating a compensatory mechanism as a response to increasing xenobiotics. Also in period 2, the MN frequency increased and BuChE and As were positively associated, suggesting co-exposure. On the other hand, in period 1, it was observed that Cr, Ni, and Pb blood levels were negatively associated with GSH-Px and GST, while MDA was positively associated with As levels. Our findings demonstrated an imbalance in endogenous antioxidants, contributing to genotoxicity and lipoperoxidation, probably in response to exposure to xenobiotics, especially carcinogenic elements (Cr, As, and Ni).

Cellular response to chemicals present in air pollution in occupationally exposed workers and its potential cancer susceptibility.

The study aimed to evaluate the potential effects of the chronic exposure to chemical agents from air pollution on phenotypic and genotypic expressions of peripheral biomarkers and tumor-related proteins in mononuclear cells. This study evaluates 85 taxi drivers (outdoor workers) and 55 non-occupationally exposed persons (NOE) to air pollution (indoor workers). The biomarkers were urinary 1-hydroxypyrene (1-OHP), for organic agents, and blood As and Ni, for inorganic agents. Oxidative stress biomarkers; protein expression of ICAM-1 (CD54), ß2-integrin, L-selectin (CD62-L), and MCP1; gene expression of ICAM-1, p53 and CD26 were performed. Urinary 1-OHP and blood As and Ni levels were increased in taxi drivers and were associated with inflammatory and oxidative stress biomarkers. These exposure biomarkers were also associated with each other, suggesting a common source of exposure. The gene expression of p53, CD26 and ICAM-1 were decreased in taxi drivers and were strongly associated between them, indicating a commom regulation point. The antioxidant non-protein thiols and lycopene were negatively associated with inflammatory biomarkers, maybe regulating the immune-response. We demonstrated, for the first time, that in occupational exposure to air pollution chemicals, oxidative and inflammatory processes are involved in the immune-regulatory process, and indirectly contribute to suppressing the p53 and CD26 expressions, increasing the risk of cancer development. On the other hand, antioxidants could contribute to improving the immune-regulation, but more studies are needed.

Trichomonas vaginalis NTPDase inhibited by lycorine modulates the parasite-neutrophil interaction.

Lycorine is an Amaryllidaceae alkaloid that presents anti-Trichomonas vaginalis activity. T. vaginalis causes trichomoniasis, the most common non-viral sexually transmitted infection. The modulation of T. vaginalis purinergic signaling through the ectonucleotidases, nucleoside triphosphate diphosphohydrolase (NTPDase), and ecto-5'-nucleotidase represents new targets for combating the parasite. With this knowledge, the aim of this study was to investigate whether NTPDase and ecto-5'-nucleotidase inhibition by lycorine could lead to extracellular ATP accumulation. Moreover, the lycorine effect on the reactive oxygen species (ROS) production by neutrophils and parasites was evaluated as well as the alkaloid toxicity. The metabolism of purines was assessed by HPLC. ROS production was measured by flow cytometry. Cytotoxicity against epithelial vaginal cells and fibroblasts was tested, as well as the hemolytic effect of lycorine and its in vivo toxicity in Galleria mellonella larvae. Our findings showed that lycorine caused ATP accumulation due to NTPDase inhibition. The alkaloid did not affect the ROS production by T. vaginalis; however, it increased ROS levels in neutrophils incubated with lycorine-treated trophozoites. Lycorine was cytotoxic against vaginal epithelial cells and fibroblasts; conversely, it was not hemolytic neither exhibited toxicity against the in vivo model of G. mellonella larvae. Overall, besides having anti-T. vaginalis activity, lycorine modulates ectonucleotidases and stimulates neutrophils to secrete ROS. This mechanism of action exerted by the alkaloid could enhance the susceptibility of T. vaginalis to host immune cell, contributing to protozoan clearance.

New pharmacological findings linked to biphenyl DHPMs, kinesin Eg5 ligands: anticancer and antioxidant effects.

Background: Dihydropyrimidin-2-thiones (DHPMs) are a class of heterocyclic compound which have been intensively investigated mainly due to their anticancer activity as kinesin Eg5 inhibitors. Materials & methods: A library of N1 aryl substituted DHPMs were tested against glioma and bladder cancer cell lines. Quantitative structure-activity relationship (QSAR) investigation was performed in order to identify key elements of DHPMs linked with their antiproliferative effect. The toxicity of most active compounds was investigated using Caenorhabditis elegans as the model. Results & conclusion: DHPMs 9, 13 and 17 have been identified as having improved activity against glioma and bladder cell lines as compared with monastrol. Flow cytometry investigations showed that the new compounds induce cell cycle arrest in phase G2/M and cell death by apoptosis. In addition, compound 13 was able to modulate the reactive oxygen species production in vivo in C. elegans. The biphenyl dihydropyrimidinthiones provided a safety profile in C. elegans.

Biochemical, hematological and immunological parameters and relationship with occupational exposure to pesticides and metals.

This study aimed to evaluate biomarkers of exposure to cholinesterase inhibitors insecticides (AChE and BuChE activities) and metals (As, Cd, Cr, Mn, Ni, and Pb blood levels) and their associations with biochemical, hematological, and immunological parameters in farmers from Southern Brazil. One hundred and sixteen individuals were divided into two groups: 62 farmers (exposed group) and 54 subjects non-occupationally exposed (NOE) to agrochemicals. Erythrocyte (AChE) and serum (BuChE) cholinesterases activities were significantly reduced as well as blood Cd and Pb levels were increased in farmers when compared to NOE group (p < 0.05). Farmers presented increased glucose and urea levels compared to NOE group, which were inversely associated with AChE and positively correlated with Cd (p < 0.05), respectively. In addition, Cd was inversely associated with the hematological cells counts, which were significantly reduced in farmers (p < 0.05). C3 complement was higher in farmers and was positively associated with blood Pb (p < 0.05). Surface protein expression analysis revealed a downregulation of LFA-1 and ICAM-1 in farmers. Inverse associations were found between LFA-1 and blood As, Cr, and Ni levels (p < 0.05). Taken together, our results pointed to a relationship between agrochemicals and metals exposure and biochemical, hematological, and immunological disorders that can lead to several chronic conditions.

Evaluation of immunological, inflammatory, and oxidative stress biomarkers in gasoline station attendants.

BACKGROUND: Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated. METHODS: A total of 66 male subjects participated in this study. The gasoline station attendants (GSA) group consisted of 38 gasoline station attendants from Rio Grande do Sul, Brazil. The non-exposed group consisted of 28 subjects who were non-smokers and who had no history of occupational exposure. Environmental and biological monitoring of BTX exposure was performed using blood and urine. RESULTS: The GSA group showed increased BTX concentrations in relation to the non-exposed group (p < 0.001). The GSA group showed elevated protein carbonyl (PCO) levels and pro-inflammatory cytokines, decreased expression of CD80 and CD86 in monocytes, and reduced glutathione S-transferase (GST) activity compared to the non-exposed group (p < 0.05). BTX levels and trans,trans-muconic acid levels were positively correlated with pro-inflammatory cytokines and negatively correlated with interleukin-10 contents (p < 0.001). Increased levels of pro-inflammatory cytokines were accompanied by increased PCO contents and decreased GST activity (p < 0.001). Furthermore, according to the multiple linear regression analysis, benzene exposure was the only factor that significantly contributed to the increased pro-inflammatory cytokines (p < 0.05). CONCLUSIONS: Taken together, these findings show the influence of exposure to BTX compounds, especially benzene, on the immunological, inflammatory, and oxidative stress biomarkers evaluated. Furthermore, the data suggest the relationship among the evaluated biomarkers of effect, which could contribute to providing early signs of damage to biomolecules in subjects occupationally exposed to BTX compounds.

Novel coumarins active against Trypanosoma cruzi and toxicity assessment using the animal model Caenorhabditis elegans.

BACKGROUND: Chagas disease (CD) is a tropical parasitic disease. Although the number of people infected is very high, the only drugs available to treat CD, nifurtimox (Nfx) and benznidazole, are highly toxic, particularly in the chronic stage of the disease. Coumarins are a large class of compounds that display a wide range of interesting biological properties, such as antiparasitic. Hence, the aim of this work is to find a good antitrypanosomal drug with less toxicity. The use of simple organism models has become increasingly attractive for planning and simplifying efficient drug discovery. Within these models, Caenorhabditis elegans has emerged as a convenient and versatile tool with significant advantages for the toxicological potential identification for new compounds. METHODS: Trypanocidal activity: Forty-two 4-methylamino-coumarins were assayed against the epimastigote form of Trypanosoma cruzi (Tulahuen 2 strain) by inhibitory concentration 50% (IC50). Toxicity assays: Lethal dose 50% (LD50) and Body Area were determined by Caenorhabditis elegans N2 strain (wild type) after acute exposure. Structure-activity relationship: A classificatory model was built using 3D descriptors. RESULTS: Two of these coumarins demonstrated near equipotency to Nifurtimox (IC50 = 5.0 ± 1 µM), with values of: 11 h (LaSOM 266), (IC50 = 6.4 ± 1 µM) and 11 g (LaSOM 231), (IC50 = 8.2 ± 2.3 µM). In C. elegans it was possible to observe that Nfx showed greater toxicity in both the LD50 assay and the evaluation of the development of worms. It is possible to observe that the efficacy between Nfx and the synthesized compounds (11 h and 11 g) are similar. On the other hand, the toxicity of Nfx is approximately three times higher than that of the compounds. Results from the QSAR-3D study indicate that the volume and hydrophobicity of the substituents have a significant impact on the trypanocidal activities for derivatives that cause more than 50% of inhibition. These results show that the C. elegans model is efficient for screening potentially toxic compounds. CONCLUSION: Two coumarins (11 h and 11 g) showed activity against T. cruzi epimastigote similar to Nifurtimox, however with lower toxicity in both LD50 and development of C. elegans assays. These two compounds may be a feasible starting point for the development of new trypanocidal drugs.

Inflammatory and oxidative stress biomarkers at protein and molecular levels in workers occupationally exposed to crystalline silica.

Workers chronically exposed to respirable crystalline silica (CS) are susceptible to adverse health effects like silicosis and lung cancer. This study aimed to investigate potential early peripheral biomarkers of inflammation and oxidative stress in miners. The subjects enrolled in this study were occupationally unexposed workers (OUW, n = 29) and workers exposed to crystalline silica (WECS), composed by miners, which were divided into two subgroups: workers without silicosis (WECS I, n = 39) and workers diagnosed with silicosis, retired from work (WECS II, n = 42). The following biomarkers were evaluated: gene expression of L-selectin, CXCL2, CXCL8 (IL-8), HO-1, and p53; malondialdehyde (MDA) plasma levels and non-protein thiol levels in erythrocytes. Additionally, protein expression of L-selectin was evaluated to confirm our previous findings. The results demonstrated that gene expression of L-selectin was decreased in the WECS I group when compared to the OUW group (p < 0.05). Regarding gene expression of CXCL2, CXCL8 (IL-8), HO-1, and p53, significant fold change decreases were observed in workers exposed to CS in relation to unexposed workers (p < 0.05). The results of L-selectin protein expression in lymphocyte surface corroborated with our previous findings; thus, significant downregulation in the WECS groups was observed compared to OUW group (p < 0.05). The MDA was negatively associated with the gene expression of CXCL-2, CXCL8 (IL-8), and p53 (p < 0.05). The participants with silicosis (WECS II) presented significant increased non-protein thiol levels in relation to other groups (p < 0.05). Taken together, our findings may contribute to help the knowledge about the complex mechanisms involved in the silicosis pathogenesis and in the risk of lung cancer development in workers chronically exposed to respirable CS.

Evaluation of hematological, biochemical parameters and thiol enzyme activity in chrome plating workers.

The most commonly used solution in chrome plating bath is chromic acid (hexavalent Cr), and a considerable amount of mists is released into the air and consequently produce hazards to workers. Thus, the aim of this study was to evaluate whether the biomarker of exposure to metals, specially Cr levels, presents associations with hematological and biochemical parameters and if they can alter the activity of enzymes that contain thiol groups such as pyruvate kinase, creatine kinase, adenylate kinase, and δ-aminolevulinate dehydratase. Fifty male chrome plating workers were used for exposed group and 50 male non-exposed workers for control group. For that, biological monitoring was performed through quantification of metals on total blood and urine by inductively coupled plasma mass spectrometry (ICP-MS) and enzyme activity was performed by spectrometry in erythrocytes. In addition, chromium levels in water was quantified and ecotoxicology assay was performed with Allium cepa test. The results demonstrated that blood and urinary chromium levels in exposed group were higher than the control group (p < 0.0001). Furthermore, decreased activity of enzymes was found in those that contain thiol groups from exposed group when compared with the control group (p < 0.001). The water analysis did not present a statistical difference between control and exposed groups (p > 0.05), demonstrating that water did not seem to be the source of contamination. In summary, our findings indicated some toxicology effects observed in the exposed group, such as thiol enzyme inhibition, mainly associated with occupational exposure in chrome plating and besides the presence of other metals, and Cr demonstrated to influence the activity of the enzymes analyzed in this research.

Exposure to environment chemicals and its possible role in endocrine disruption of children from a rural area.

Endocrine disrupting chemicals (EDCs), including pesticides and metals, are present in rural areas, endangering the health of exposed populations. This work aimed to investigate the possible association between the exposure to these xenobiotics and thyroid dysfunction in children living in a rural community of Southern Brazil. Fifty-four children aged 5-16 years participated in this study. Peripheral biomarker evaluations were performed in periods of low and high exposure to pesticides. Thyroid ultrasonography was evaluated in the high exposure period. Blood levels of chromium (Cr), manganese (Mn), mercury (Hg), and lead (Pb), as well as hair Pb levels were positively correlated with thyroid stimulating hormone (TSH) concentrations and negatively associated with free thyroxine (fT4) levels in the low exposure period. Prolactin was positively associated with hair Mn in both periods. In the ultrasound tests, the majority of children presented a normal echogenicity of thyroid. Glucose was inversely associated with the biomarker of exposure to cholinesterase inhibitor insecticides, butyrylcholinesterase (BuChE). Lipid profile was above the recommended levels in both periods. In summary, our results show that children environmentally exposed to a mixture of xenobiotics in an agricultural community may have health impairments, especially on thyroid function, dyslipidemia, and glucose homeostasis disruption.

Inflammatory and oxidative stress parameters as potential early biomarkers for silicosis.

Workers involved in mining activities are exposed to crystalline silica, which leads to constant pulmonary inflammatory reactions and severe oxidative damage, resulting in silicosis. In this work, we aimed to evaluate inflammatory and oxidative stress parameters as potential early biomarkers of effect to assess crystalline silica toxicity in workers who had occupational exposure during mining. We enrolled 38 workers exposed to crystalline silica (WECS), 24 individuals with silicosis (IWS), and 30 occupationally unexposed workers (OUW), a total of 92 participants. The WECS were divided into 2 groups, according to the time of exposure: 19 workers with 1-15 years of occupational exposure (WECS I) and 19 workers with >16 years of occupational exposure (WECS II). The inflammatory parameters assessed were L-selectin, ß-2 integrin, and intercellular adhesion molecule-1 (ICAM-1) surface protein expression in lymphocytes and monocytes, complement C3 and C4, high sensitivity C-reactive protein (hsCRP), and adenosine deaminase (ADA) in serum. Plasma levels of malondialdehyde (MDA) and serum levels of vitamin C were determined as biomarkers of oxidative stress. Biochemical and hematological parameters were also investigated. L-selectin surface protein expression was significantly decreased in the WECS II group (p < 0.05), indicating the importance of this immune system component as a potential marker of crystalline-silica-induced toxicity. The MDA levels were significantly increased in the WECS I, WECS II, and IWS groups compared to the OUW group (p < 0.05). Vitamin C levels were decreased, while C3, hsCRP, ADA, and aspartate aminotransferase (AST) levels were increased in the IWS group compared to the OUW group (p < 0.05). Glucose and urea levels were significantly higher in the WECS I, II, and IWS groups compared to the OUW group (p < 0.05). Negative partial association was found between L-selectin and time of exposure (p < 0.001), supporting the relevance of this biomarker evaluation in long-term exposure to crystalline silica. Significant associations were also observed among inflammatory and oxidative stress biomarkers. Therefore, our results demonstrated the relevance of L-selectin as a potential peripheral biomarker for monitoring crystalline silica-induced toxicity in miners after chronic exposure, before silicosis has developed. However, more studies are necessary for better understanding of the use L-selectin as an early biomarker in exposed workers.

The role of B7 costimulation in benzene immunotoxicity and its potential association with cancer risk.

Benzene is a recognized human carcinogen; however, there are still some gaps in the knowledge regarding the mechanism of toxicity of this organic solvent and potential early biomarkers for the damage caused by it. In a previous study, our research group demonstrated that the adhesion molecules of the immune system (B7.1 and B7.2) could be potential biomarkers in the early detection of immunotoxicity caused by benzene exposure. Therefore, this study was developed to deepen the understanding regarding this important topic, aiming to contribute to the comprehension of the benzene toxicity mechanism mediated by B7.1 and B7.2 and its potential association with the risk of carcinogenicity. B7.1 and B7.2 protein expression in blood monocytes and B7.1 and B7.2 gene expression in PBMCs were evaluated. Additionally, complement C3 and C4 levels in serum were measured, as well as p53 gene expression in PBMCs. Seventy-four gas station workers (GSW group) and 71 non-occupationally exposed subjects (NEG) were evaluated. Our results demonstrated decreased levels of B7.1 and B7.2 protein and gene expression in the GSW group compared to the NEG (n = 71) (p < 0.01). Along the same lines, decreased levels of the complement system were observed in the GSW group (p < 0.01), demonstrating the impairment of this immune system pathway as well. Additionally, a reduction was observed in p53 gene expression in the GSA group (p < 0.01). These alterations were associated with both the benzene exposure biomarker evaluated, urinary trans, trans-muconic acid, and with exposure time (p < 0.05). Moreover, strong correlations were observed between the gene expression of p53 vs. B7.1 (r = 0.830; p < 0.001), p53 vs. B7.2 (r = 0.685; p < 0.001), and B7.1 vs. B7.2 (r = 0.702; p < 0.001). Taken together, these results demonstrate that the immune system co-stimulatory molecule pathway is affected by benzene exposure. Also, the decrease in p53 gene expression, even at low exposure levels, reinforces the carcinogenicity effect of benzene in this pathway. Therefore, our results suggest that the promotion of immune evasion together with a decrease in p53 gene expression may play an important role in the benzene toxicity mechanism. However, further and targeted studies are needed to confirm this proposition.

Protective effect of Uncaria tomentosa extract against oxidative stress and genotoxicity induced by glyphosate-Roundup® using zebrafish (Danio rerio) as a model.

Oxidative stress and DNA damage are involved in the glyphosate-based herbicide toxicity. Uncaria tomentosa (UT; Rubiaceae) is a plant species from South America containing bioactive compounds with known beneficial properties. The objective of this work was to evaluate the antioxidant and antigenotoxic potential of UT extract in a model of acute exposure to glyphosate-Roundup® (GR) in zebrafish (Danio rerio). We showed that UT (1.0 mg/mL) prevented the decrease of brain total thiols, the increase of lipid peroxidation in both brain and liver, and the decrease of liver GPx activity caused after 96 h of GR (5.0 mg/L) exposure. In addition, UT partially protected against the increase of micronucleus frequency induced by GR exposure in fish brain. Overall, our results indicate that UT protects against damage induced by a glyphosate-based herbicide by providing antioxidant and antigenotoxic effects, which may be related to the phenolic compounds identified in the extract.

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.

Association between inflammation processes, DNA damage, and exposure to environmental pollutants.

Environmental exposure to pollutants, especially polycyclic aromatic hydrocarbons (PAHs), could lead to carcinogenesis development. However, there is a gap on the mechanisms involved in this effect. Therefore, the aim of this study was to investigate the potential relationship between exposure to environmental air pollution and inflammation process in DNA damage in taxi drivers. This study included 45 taxi drivers and 40 controls; non-smokers composed both groups. Biological monitoring was performed through quantification of urinary 1-hydroxypyrene (1-OHP). ICAM-1 (CD54) expression, NTPDase activity, inflammatory cytokine (IL-1ß, IL-6, IL-10, TNF-α and IFN-γ) levels, and comet and micronucleus assays were evaluated. The results demonstrated that 1-OHP levels, ICAM-1 expression, NTPDase activity, and DNA damage biomarkers (% tail DNA and micronucleus frequency) were increased in taxi drivers compared to the control group (p < 0.01). Moreover, significant associations were found between 1-OHP levels and ICAM-1 expression, % tail DNA, and micronucleus frequency (p < 0.05). Besides, pro-inflammatory cytokine levels were positively correlated to % tail DNA and micronucleus frequency (p < 0.001). Our findings suggest an important association between environmental exposure to air pollution with increase of ICAM-1 expression and NTPDase activity in taxi drivers. Additionally, the multiple regression linear-analysis demonstrated association between IL-6 and DNA damage. Thus, the present study has provided important evidence that, in addition to environmental exposure to air pollutants, the inflammation process may contribute to DNA damage.

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.

Early hematological and immunological alterations in gasoline station attendants exposed to benzene.

INTRODUCTION: Elucidation of effective biomarkers may provide tools for the early detection of biological alterations caused by benzene exposure and may contribute to the reduction of occupational diseases. This study aimed to assess early alterations on hematological and immunological systems of workers exposed to benzene. METHODS: Sixty gasoline station attendants (GSA group) and 28 control subjects were evaluated. Environmental and biological monitoring of benzene exposure was performed in blood and urine. The potential effect biomarkers evaluated were δ-aminolevulinate dehydratase (ALA-D) activity, CD80 and CD86 expression in lymphocytes and monocytes, and serum interleukin-8 (IL-8). The influence of confounding factors and toluene co-exposure were considered. RESULTS: Although exposures were below ACGIH (American Conference of Governmental Industrial Hygienists) limits, reduced ALA-D activity, decreased CD80 and CD86 expression in monocytes and increased IL-8 levels were found in the GSA group compared to the control subjects. Furthermore, according to multiple linear regression analysis, benzene exposure was associated to a decrease in CD80 and CD86 expression in monocytes. CONCLUSIONS: These findings suggest, for the first time, a potential effect of benzene exposure on ALA-D activity, CD80 and CD86 expression, IL-8 levels, which could be suggested as potential markers for the early detection of benzene-induced alterations.