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.

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.

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.

Liver δ-aminolevulinate dehydratase activity is inhibited by neonicotinoids and restored by antioxidant agents.

Neonicotinoids represent the most used class of insecticides worldwide, and their precursor, imidacloprid, is the most widely marketed. The aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ-aminolevulinate dehydratase (δ-ALA-D), protective effect of potential antioxidants against this potential effect and presence of chemical elements in the constitution of this pesticide. We observed that δ-ALA-D activity was significantly inhibited by imidacloprid at all concentrations tested in a dose-dependent manner. The IC50 value was obtained and used to evaluate the restoration of the enzymatic activity. δ-ALA-D inhibition was completely restored by addition of dithiotreitol (DTT) and partly by ZnCl2, demonstrating that the inhibition occurs by oxidation of thiol groups and by displacement of the Zn (II), which can be explained by the presence of chemical elements found in the constitution of pesticides. Reduced glutathione (GSH) had the best antioxidant effect against to δ-ALA-D inhibition caused by imidacloprid, followed by curcumin and resveratrol. It is well known that inhibition of the enzyme δ-ALA-D may result in accumulation of its neurotoxic substrate (δ-ALA), in this line, our results suggest that further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and the involvement of antioxidants in cases of poisoning by neonicotinoids.

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.

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.

Atherosclerotic process in taxi drivers occupationally exposed to air pollution and co-morbidities.

Consistent evidence has indicated that the exposure to environmental air pollution increases the risk of cardiovascular disease. This study aimed to evaluate the possible effects of occupational exposure to air pollution, especially to polycyclic aromatic hydrocarbons (PAHs), and the influence of co-morbidities on the atherosclerotic process and inflammation. For that, biomarkers of exposure such as 1-hydroxypyrene urinary, oxidative damage and markers of cardiovascular risk were determined in plasma, serum and blood. In addition, inflammation models such as carotid intima-media thickness and serum inflammatory cytokines were analyzed in 58 taxi drivers with and without co-morbidity. The results demonstrated that considering only taxi drivers without co-morbidities, 15% presented carotid intima-media thickness above reference values. For the first time it has been demonstrated that urinary 1-hydroxypyrene levels were associated with carotid intima-media thickness and with serum homocysteine levels. The multiple linear regression analysis showed that several factors may contribute to the increased carotid intima-media thickness, among which age, interleukin-6, fibrinogen and exposure to PAHs stand out. In summary, our results suggest that chronic occupational exposure to atmospheric pollution could be an additional contributor to the atherogenesis process, leading to impaired vascular health. Moreover, carotid intima-media thickness, serum homocysteine levels, fibrinogen and the total cholesterol/HDL-c ratio could be suggested as preventive measures to monitor drivers' health.

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 the pharmacological activity of the Alternanthera brasiliana aqueous extract.

CONTEXT: Alternanthera brasiliana (L.) Kuntze (Amarantaceae) is widely used in Brazilian traditional medicine as an analgesic, anti-inflammatory and antibacterial. OBJECTIVE: To investigate the potential anti-inflammatory, analgesic, anxiolytic, and locomotor effect of the infusions in preclinical models. MATERIALS AND METHODS: Anti-inflammatory activity was evaluated by a carrageenan-induced pleurisy test in Wistar rats (200 and 400 mg/kg, n = 6-7). Analgesic activity was evaluated by the number of abdominal contractions induced by 0.6% acetic acid administered to Swiss mice (25, 50, 100, 200, and 400 mg/kg, n = 10). Effects on the central nervous system (CNS) were evaluated in Wistar rats (100, 200, and 400 mg/kg, n = 10) using open field and plus maze models. RESULTS AND DISCUSSION: Possible anti-inflammatory activity was indicated by the significant reduction of 19.8% for 200 mg/kg (p < 0.05) and 23.9% for 400 mg/kg (p < 0.05) of polymorphonuclear cells in pleural exudate. Analgesic activity was suggested by the significant reduction (p < 0.01) of number of abdominal contractions for all doses under study. No anxiolytic effect was noted, but there was an increase in the number of rearings in the group of rats treated with 100 mg/kg dose (p < 0.05). CONCLUSIONS: Our findings suggest that the aqueous extract of the leaves of A. brasiliana has a potential pharmacological effect on inflammation and pain.