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1.
Chemosphere ; 263: 127857, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32854004

RESUMO

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.


Assuntos
Poluição do Ar , Neoplasias , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , Biomarcadores , Humanos , Neoplasias/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Estresse Oxidativo , Pirenos/análise
2.
Artigo em Inglês | MEDLINE | ID: mdl-32805194

RESUMO

Ochratoxin A (OTA) is a mycotoxin found in grape products and oxidative stress has been reported as an important mechanism involved in its toxicity, classified as possible carcinogenic to humans. Conversely, phenolics are known bioactive compounds in grapes and display great antioxidant properties. However, the biological effects of the concomitant presence of phenolic compounds and OTA remains unclear. The aim of this study was to evaluate, for the first time, the effect of OTA presence in Cabernet Sauvignon wine on antioxidant activity in vitro and on oxidative stress markers in vivo. In addition, the phenolic composition of wine was evaluated by LC-DAD-MS/MS. In vitro assays were based on spectrophotometric methods, while in vivo assays were performed evaluating oxidative stress markers in the nematode Caenorhabditis elegans, an alternative model to animal testing. A total of 23 phenolic compounds were identified in the Cabernet sauvignon red wine, including the anthocyanins delphinidin-3-O-glicoside and malvidin-3-O-glicoside, the flavonol quercetin-3-O-glucuronide and the phenolic acids caffeic, verbascoside and caftaric. Trans-resveratrol and trans-piceid were the only stilbenes found in the samples. OTA presence in the red wine was accompanied by reduction in GSH content and increase in hydroxyl radical generation in vitro. The presence of OTA in wine also increased lipoperoxidation and induced overexpression of the antioxidant enzymes superoxide dismutase and catalase in vivo. This study demonstrates that OTA presence in red wine can reduce its antioxidant potential in vitro and induces oxidative stress in vivo, without affecting the phenolic compounds levels in the samples. Thus, this work provides insights into the negative effects of the presence of OTA in wine, not only by its known toxicity, but also by prejudicing the antioxidant potential of wine. It is important to be aware of these effects when developing a complete description of OTA toxicity in humans.

3.
Future Med Chem ; 12(12): 1137-1154, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32513026

RESUMO

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.

4.
Environ Sci Pollut Res Int ; 27(23): 29291-29302, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32436094

RESUMO

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.


Assuntos
Exposição Ocupacional/análise , Praguicidas/análise , Brasil , Fazendeiros , Humanos , Metais
5.
Drug Chem Toxicol ; : 1-8, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32106715

RESUMO

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.

6.
J Appl Toxicol ; 40(3): 363-372, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31755144

RESUMO

Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1-benzylpiperazine (BZP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC50 for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm, respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.

7.
BMC Pharmacol Toxicol ; 20(Suppl 1): 80, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31852511

RESUMO

BACKGROUND: Melatonin has been described in the literature as a potent antioxidant. However, melatonin presents variable, low bioavailability and a short half-life. The use of polymeric nanoparticulated systems has been proposed for controlled release. Thus, the purpose of this study was to investigate the action of melatonin-loaded lipid-core nanocapsules (Mel-LNC) in the antioxidant system of Caenorhabditis elegans, and the possible protective effect of this formulation against lipid peroxidation caused by paraquat (PQ). METHODS: The suspensions were prepared by interfacial deposition of the polymer and were physiochemically characterized. C. elegans N2 wild type and transgenic worm CF1553, muls84 [sod-3p::gfp; rol6(su1006)] were obtained from the Caenorhabditis Genetics Center (CGC). The worms were divided into 5 groups: Control, PQ 0.5 mM, PQ 0.5 mM + Mel-LNC 10 µg/mL, PQ + unloaded lipid-core nanocapsules (LNC), and PQ + free melatonin (Mel) 10 µg/mL. The lipid peroxidation was assessed through thiobarbituric acid (TBARS) levels and the fluorescence levels of the transgenic worms expressing GFP were measured. RESULTS: The LNC and Mel-LNC presented a bluish-white liquid, with pH values of 5.56 and 5.69, respectively. The zeta potential was - 6.4 ± 0.6 and - 5.2 ± 0.2, respectively. The mean particle diameter was 205 ± 4 nm and 203 ± 3 nm, respectively. The total melatonin content was 0.967 mg/ml. The TBARS levels were significantly higher in the PQ group when compared to the control group (p < 0.001). Mel-LNC reduced TBARS levels to similar levels found in the control group. Moreover, only Mel-LNC significantly enhanced the SOD-3 expression (p < 0.05). Mel-LNC was capable of protecting C. elegans from lipid peroxidation caused by PQ and this was not observed when free melatonin was used. Moreover, Mel-LNC increased the fluorescence intensity of the transgenic strain that encodes the antioxidant enzyme SOD-3, demonstrating a possible mechanism of protection from PQ-induced damage. CONCLUSION: These findings demonstrated that melatonin, when associated with nanocapsules, had improved antioxidant properties and the protective activity against PQ-induced lipid peroxidation could be associated with the activation of antioxidant enzymes by Mel-LNC in C. elegans.


Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Portadores de Fármacos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Melatonina/farmacologia , Nanocápsulas/química , Paraquat/toxicidade , Superóxido Dismutase/genética , Animais , Antioxidantes/química , Caenorhabditis elegans/enzimologia , Composição de Medicamentos , Lipídeos/química , Melatonina/química , Tamanho da Partícula
8.
BMC Pharmacol Toxicol ; 20(Suppl 1): 75, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31852532

RESUMO

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.


Assuntos
Poluentes Ocupacionais do Ar/análise , Derivados de Benzeno/urina , Monitoramento Biológico/métodos , Citocinas/urina , Biomarcadores Ambientais/imunologia , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos dos fármacos , Adulto , Poluentes Ocupacionais do Ar/efeitos adversos , Antígeno B7-1/sangue , Antígeno B7-1/urina , Antígeno B7-2/sangue , Antígeno B7-2/urina , Derivados de Benzeno/toxicidade , Brasil , Citocinas/sangue , Biomarcadores Ambientais/efeitos dos fármacos , Humanos , Masculino , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/imunologia , Carbonilação Proteica/efeitos dos fármacos
9.
BMC Pharmacol Toxicol ; 20(Suppl 1): 76, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31852548

RESUMO

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.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Cumarínicos/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/toxicidade , Concentração Inibidora 50 , Dose Letal Mediana , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Tripanossomicidas/toxicidade , Trypanosoma cruzi/crescimento & desenvolvimento
10.
Mutat Res ; 841: 8-13, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31138412

RESUMO

Graphene is a two-dimensional (2D) monolayer of carbon atoms, tightly packed, forming a honey comb crystal lattice, with physical, chemical, and mechanical properties greatly used for energy storage, electrochemical devices, and in nanomedicine. Many studies showed that nanomaterials have side-effects on health. At present, there is a lack of information regarding graphene and its derivatives including their cardiotoxic properties. The aim of the present study was to evaluate the toxicity of nano-graphene oxide (nano-GO) in the rat cardiomyoblast cell line H9c2 and the involvement of oxidative processes. The cell viability was evaluated with the fluorescein diacetate (FDA)/propidium iodide (PI) and in the trypan blue exclusion assay, furthermore mitochondrial membrane potential and production of free radicals were measured. Genotoxicity was evaluated in comet assay and low molecular weight DNA experiment. Reduction of cell viability with 20, 40, 60, 80, and 100 µg/mL nano-GO was observed after 24 h incubation. Besides, nano-GO induced a mitochondrial hyperpolarization and a significant increase of free radicals production in the same concentrations. DNA breaks were observed at 40, 60, 80, and 100 µg/mL. This DNA damage was accompanied by a significant increase in LMW DNA only at 40 µg/mL. In conclusion, the nano-GO caused cardiotoxicity in our in vitro model, with mitochondrial disturbances, generation of reactive species and interactions with DNA, indicating the importance of the further evaluation of the safety of nanomaterials.


Assuntos
Cardiotoxicidade/etiologia , Grafite/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Nanopartículas/efeitos adversos , Nanoestruturas/efeitos adversos , Ratos
11.
Drug Chem Toxicol ; 42(5): 509-518, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29644883

RESUMO

Degradation kinetics of oral anticoagulant rivaroxaban (RIV) was assessed in acid and alkaline media and while exposed to UVC radiation. Among all stress conditions tested, kinetic degradation process was better described by a zero-order model. A stability indicating method was validated for the analysis of the anticoagulant RIV in tablets by high-performance liquid chromatography. Robustness was evaluated with a two-level Plackett-Burman experimental design. The effect of acute exposition of the human hepatoblastoma HepG2 cell line to RIV stressed samples (100 and 500 µM) was assessed through in vitro toxicity tests. MTT reduction, neutral red uptake, mitochondrial membrane potential, and low molecular weight DNA diffusion assays were employed for cytotoxicity evaluation (5×104 cells/well). The genotoxic potential was assessed by comet assay (2×104 cells/well). Acute toxicity to HepG2 cells was assessed after 24 h incubation with sample solutions, for each test. A direct relationship between the increased amount of alkaline degradation products and higher cytotoxic potential was found. Results obtained by viability assay investigations support the concerns on risks associated with acute toxicity and genotoxicity of pharmaceutical samples containing degradation products as impurities.


Assuntos
Anticoagulantes/toxicidade , Dano ao DNA , Rivaroxabana/toxicidade , Anticoagulantes/efeitos da radiação , Técnicas de Cultura de Células , Ensaio Cometa , Estabilidade de Medicamentos , Células Hep G2 , Humanos , Hidrólise , Cinética , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rivaroxabana/efeitos da radiação , Testes de Toxicidade
12.
Environ Sci Pollut Res Int ; 26(2): 1394-1405, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30426371

RESUMO

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.


Assuntos
Biomarcadores/sangue , Inflamação/sangue , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/fisiologia , Dióxido de Silício/toxicidade , Adulto , Estudos de Casos e Controles , Quimiocina CXCL2/sangue , Quimiocina CXCL2/genética , Expressão Gênica , Genes p53 , Heme Oxigenase-1/sangue , Heme Oxigenase-1/genética , Humanos , Inflamação/induzido quimicamente , Interleucina-8/sangue , Interleucina-8/genética , Selectina L/sangue , Selectina L/genética , Masculino , Malondialdeído/sangue , Mineração , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos dos fármacos , Silicose/etiologia
13.
Medchemcomm ; 9(6): 995-1010, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108989

RESUMO

An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs) substituted with N-1 aryl groups derived from monastrol was designed and synthesized in order to discover a more effective Eg5 ligand than the template. Based on molecular docking studies, four ligands were selected to perform pharmacological investigations against two glioma cell lines. The results led to the discovery of two original compounds, called 20h and 20e, with an anti-proliferative effects, achieving IC50 values of about half that of the IC50 of monastrol in both cell lines. As with monastrol, flow cytometry analyses showed that the 20e and 20h compounds induced cell cycle arrest in the G2/M phase, and immunocytochemistry essays revealed the formation of monopolar spindles due to Eg5 inhibition without any toxicity to Caenorhabditis elegans.

14.
Environ Res ; 167: 488-498, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30142624

RESUMO

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.


Assuntos
Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Praguicidas/efeitos adversos , Adolescente , Biomarcadores/sangue , Brasil , Criança , Pré-Escolar , Humanos , Metais Pesados/sangue , População Rural , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue
15.
Toxicol Appl Pharmacol ; 355: 138-146, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29959998

RESUMO

The aim of this study was to evaluate the acute toxicity of the association of energy drink and alcohol in male Wistar rats. Animals were treated by oral gavage with 10 ml/kg distilled water (control); 10 ml/kg energy drink (ED10); 3.2 mg/kg caffeine + 40 mg/kg taurine; 2 g/kg alcohol 20%; 2 g/kg alcohol 20% + ED10; and 2 g/kg alcohol 20% + 3.2 mg/kg caffeine + 40 mg/kg taurine. Behavioral alterations were observed for 6 h after treatment. Animals presented significant differences in the frequency of rearing, ambulation, grooming, wakefulness and tachypnea along time. Caffeine + taurine increased the levels of TBARS and total thiols in kidneys. ED10 increased lipoperoxidation in liver. The association of ED10 + alcohol induced nephrotoxicity observed by the increase of urinary N-acetyl-ß-d-glucosaminidase (NAG) activity. Histopathological analysis showed the presence of congestion and hydropic and hyaline degenerations in the livers of ED10 + alcohol treated rats, and hemorrhage in the liver of alcohol + caffeine + taurine group. In kidneys, hyaline degeneration was observed in ED10; ED10 + alcohol; caffeine + taurine; and alcohol + caffeine + taurine. Hemorrhage was present in the kidneys of all groups. The combination of energy drinks and alcohol is not safe for the consumers. Therefore, precautionary measures should be disseminated among risk populations, especially the teenagers.


Assuntos
Bebidas Alcoólicas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Bebidas Energéticas/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/patologia , Animais , Comportamento Animal/efeitos dos fármacos , Cafeína/toxicidade , Estimulantes do Sistema Nervoso Central/toxicidade , Asseio Animal/efeitos dos fármacos , Hemorragia/induzido quimicamente , Hemorragia/patologia , Rim/patologia , Fígado/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Taquipneia/induzido quimicamente , Taquipneia/patologia , Taurina/toxicidade , Vigília/efeitos dos fármacos
16.
Environ Res ; 166: 91-99, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29883905

RESUMO

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.


Assuntos
Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Benzeno/toxicidade , Neoplasias/imunologia , Exposição Ocupacional , Biomarcadores , Carcinógenos , Estudos de Casos e Controles , Complemento C3/imunologia , Complemento C4/imunologia , Humanos , Proteína Supressora de Tumor p53/genética
17.
Clin Chim Acta ; 484: 305-313, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29860036

RESUMO

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.


Assuntos
Ácido Ascórbico/sangue , Inflamação/sangue , Inflamação/diagnóstico , Malondialdeído/sangue , Estresse Oxidativo , Silicose/sangue , Silicose/diagnóstico , Biomarcadores/sangue , Humanos
18.
Food Chem Toxicol ; 109(Pt 1): 60-67, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28866331

RESUMO

Microcystin-LR (MIC-LR) is a hepatotoxin, with toxicity mechanisms linked to oxidative stress. Besides, neurotoxic effects of MIC-LR have recently been described. Herein, we evaluated the effects of environmentally important concentrations of MIC-LR (1, 10, 100, 250, and 500 µg/L) on oxidative stress markers and the survival rate of the nematode Caenorhabditis elegans (C. elegans). In addition, a possible protective effect of the carotenoid lutein (LUT) extracted from marigold flowers against MIC-LR toxicity was investigated. Higher concentrations (250 and 500 µg/L) of MIC-LR induced the generation of reactive oxygen species (ROS) and resulted in a survival loss in C elegans. Meanwhile, all MIC-LR concentrations caused an increase in the superoxide dismutase (SOD) expression, while catalase (CAT) expression was only affected at 500 µg/L. The carotenoid LUT prevented the ROS generation, impairment in the CAT expression, and the survival loss induced by MIC-LR in C. elegans. Our results confirm the toxicity of MIC-LR even in a liver-lacking invertebrate and the involvement of oxidative events in this response. Additionally, LUT appears to be able to mitigate the MIC-LR toxic effects.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Luteína/administração & dosagem , Microcistinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Tagetes/química , Animais , Caenorhabditis elegans/metabolismo , Catalase/metabolismo , Flores/química , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Toxinas Marinhas , Espécies Reativas de Oxigênio/metabolismo
19.
Environ Sci Pollut Res Int ; 24(28): 22673-22678, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28812184

RESUMO

Ozone helps decontamination environments due to its oxidative power, however present toxicity when it is in high concentrations, by long periods of exposition. This study aimed to assess the safety of ozone generator air purifier at concentrations of 0.05 ppm in rats exposed to 3 and 24 h/day for 14 and 28 days. No significant differences are observed between groups in clinical signs, feed and water intake, relative body weight gain and relative weight of organs, macroscopy and microscopy of lungs, and oxidative plasma assay. In this exposure regime, ozone does not cause genotoxicity and no significant changes in pulmonary histology indicative of toxicity. Ozone generated in low concentrations, even in exposure regimes above the recommended is safe, both acute and sub-acute exposition.


Assuntos
Ar Condicionado/normas , Ozônio/análise , Ozônio/toxicidade , Ar Condicionado/instrumentação , Animais , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Ensaio Cometa , Relação Dose-Resposta a Droga , Exposição por Inalação , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Testes para Micronúcleos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
20.
Environ Sci Pollut Res Int ; 24(3): 2851-2865, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27838906

RESUMO

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.


Assuntos
Exposição Ambiental , Nefropatias , Tabaco , Agricultura , Biomarcadores/metabolismo , Butirilcolinesterase , Criança , Cromo/sangue , Cotinina/urina , Feminino , Humanos , Masculino , Malondialdeído/urina , Nicotina/análise , Praguicidas/toxicidade , População Rural
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