RESUMO
Background: Pesticides are indispensable for the cultivation of crops, especially those of economic importance, such as soybeans. Data on the annual use of herbicides in crops show that they correspond to 50%, making it the most used in agriculture. Aim: Therefore, the aim of this study was to evaluate the toxicity of the three commercial herbicides (clomazone, glyphosate, and sulfentrazone) in THP-1 cells. Methods: Cells were incubated with 0-5,000 mg/L of the herbicides for 24 h at 37 °C for cytotoxicity evaluation. Additionally, a few toxicological pathways such as reactive species generation, mitochondrial impairment, and interleukin profile, which have been previously involved in the toxicity of pesticides, were also evaluated. Results: A potential immunotoxic effect of the herbicides on THP-1 cells was observed, especially glyphosate, as it is a powerful agent of cellular immunotoxicity. It was also possible to verify an increase in oxidative stress and IL-8 levels and mitochondrial dysfunction. Conclusion: All herbicides showed cytotoxic effects in THP-1 monocytes, which were related to mitochondrial impairment.
RESUMO
Bladder cancer is the fourth most common malignancy in men. It can present along the entire continuum of severity, from mild to well-differentiated disease to extremely malignant tumors with low survival rates. Human RAS genes are the most frequently mutated oncogenes in human cancers, and the critical role of aberrant Ras protein function in carcinogenesis is well established. Therefore, considerable efforts have been devoted to the development of anti-Ras inhibitors for cancer treatment. This study presents the biphenyl dihydropyrimidinone LaSOM 335 with high activity against T24 bladder cancer cells (IC50 = 10.73 ± 0.53 µM) and selectivity of cytotoxicity for this cancer cell line compared to two non-cancer cell lines investigated. Furthermore, we also show that this compound reduced vulvar development in the mutant let-60 gene of Caenorhabditis elegans. Let-60 is a homolog of the mammalian Ras gene. In addition, we observed that LaSOM 335 inhibits the enzymatic activity of CD73 and decreases CD73 expression. Possibly, this expression decrease is due to downstream EGFR signaling via the Ras-Raf-ERK pathway, that directly regulates CD73 expression via ERK1/2. Evidence suggests that non-immunomodulating functions of CD73 play an equally important role for cancer cell survival, progression, and migration. Regarding we also notice that LaSOM 335 was safe in the in vivo model of C. elegans. The set of these findings makes this biphenyl dihydropyrimidinone a promising candidate for further investigations in the bladder cancer field.
Assuntos
Genes ras , Neoplasias da Bexiga Urinária , Masculino , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Mamíferos/genética , Mamíferos/metabolismoRESUMO
Etidocaine (EDC) is a long-acting local anesthetic of the aminoamide family whose use was discontinued in 2008 for alleged toxicity issues. Ionic gradient liposomes (IGL) are nanostructured carriers for which an inner/outer gradient of ions increases drug upload. This work describes IGLEDC, a formulation optimized by Design of Experiments, composed of hydrogenated soy phosphatidylcholine:cholesterol:EDC, and characterized by DLS, NTA, TEM/Cryo-TEM, DSC and 1H NMR. The optimized IGL showed significant encapsulation efficiency (41 %), good shelf stability (180 days) and evidence of EDC interaction with the lipid bilayer (as seen by DSC and 1H NMR results) that confirms its membrane permeation. In vitro (release kinetics and cytotoxicity) tests showed that the encapsulation of EDC into the IGL promoted sustained release for 24 h and decreased by 50 % the intrinsic toxicity of EDC to Schwann cells. In vivo IGLEDC decreased the toxicity of EDC to Caenorhabditis elegans by 25 % and extended its anesthetic effect by one hour, after infiltrative administration, at clinically used (0.5 %) concentration, in rats. Thus, this novel drug delivery system is a promise for the possible reintroduction of EDC in clinics, aiming at the control of operative and postoperative pain.
Assuntos
Anestesia , Lipossomos , Ratos , Animais , Lipossomos/química , Etidocaína , Anestésicos Locais , Íons/químicaRESUMO
Liposomes are among the most studied nanostructures. They are effective carriers of active substances both in the clinical field, such as delivering genes and drugs, and in the food industry, such as promoting the controlled release of bioactive substances, including food preservatives. However, toxicological screenings must be performed to ensure the safety of nanoformulations. In this study, the nematode Caenorhabditis elegans was used as an alternative model to investigate the potential in vivo toxicity of nanoliposomes encapsulating the antimicrobial peptide nisin. The effects of liposomes containing nisin, control liposomes, and free nisin were evaluated through the survival rate, lethal dose (LD50), nematode development rate, and oxidative stress status by performing mutant strain, TBARS, and ROS analyses. Due to its low toxicity, it was not possible to experimentally determine the LD50 of liposomes. The survival rates of control liposomes and nisin-loaded liposomes were 94.3 and 73.6%, respectively. The LD50 of free nisin was calculated as 0.239 mg mL-1. Free nisin at a concentration of 0.2 mg mL-1 significantly affected the development of C. elegans, which was 25% smaller than the control and liposome-treated samples. A significant increase in ROS levels was observed after exposure to the highest concentrations of liposomes and free nisin, coinciding with a significant increase in catalase levels. The treatments induced lipid peroxidation as evaluated by TBARS assay. Liposome encapsulation reduces the deleterious effect on C. elegans and can be considered a nontoxic delivery system for nisin.
Assuntos
Antibacterianos , Nanopartículas , Nisina , Fosfatidilcolinas , Animais , Antibacterianos/toxicidade , Caenorhabditis elegans , Lecitinas , Lipossomos , Nisina/toxicidade , Espécies Reativas de Oxigênio , Substâncias Reativas com Ácido Tiobarbitúrico , Sistemas de Liberação de MedicamentosRESUMO
This study characterized and investigated the toxicity of two multi-walled carbon nanotubes (MWCNT) NM-401 and NM-403 at 60 and 180 µg after four repeated intratracheal instillations; follow-up times were 3, 7, 30, and 90 days after the last instillation. NM-401 was needle-like, long, and thick, while NM-403 was entangled, short, and thin. Both MWCNT types induced transient pulmonary and systemic alterations in renal function and oxidative lipid damage markers in recent times. Animals showed general toxicity in the immediate times after exposures, in addition to increased pulmonary LDH release at day 3. In further times, decreased liver and kidney relative weights were noted at higher MWCNT doses. Lung histological damages included pulmonary fibrosis, for both MWCNT types, similarly to asbestos; single liver and kidney histological alterations were present. Repeated instillations led to persistent pulmonary damage at low doses, and possibly the extrapulmonary effects may be associated with the consecutive exposures.
Assuntos
Nanotubos de Carbono , Fibrose Pulmonar , Animais , Nanotubos de Carbono/toxicidade , Pulmão , Fibrose Pulmonar/patologia , Fatores de Tempo , Líquido da Lavagem BroncoalveolarRESUMO
OBJECTIVE: To estimate the prevalence of vitamin A deficiency (VAD) in children and associated risk factors. DESIGN: Analysis of data from a cross-sectional multicentre study performed in the primary care units of the municipalities from January to June 2015. The children's legal guardians answered a socio-economic questionnaire, and the children's blood samples were obtained by venipuncture. Plasma retinol was determined by HPLC. Plasma retinol values of <0·70 µmol/l were considered VDA. Poisson multiple regression with robust variance was used. Values of P < 0·05 were considered significant. The data were analysed in the SPSS software, 21.0. SETTING: Forty-eight poorest municipalities in the South Region of Brazil. PARTICIPANTS: Children (n 1503) aged 12-59 months. RESULTS: The prevalence of VAD in the sample was 1·9 % (95 % CI (0·5, 6·8)). The following risk factors were associated with the outcome in the final explanatory model: family received Bolsa Familia program benefits (PR = 3·19; 95 % CI (1·69, 6·02)), child was not being breastfed (PR = 5·22; 95 % CI (1·68, 16·18)) and stunting (PR = 4·75; 95 % CI (2·10, 10·73)). CONCLUSIONS: VAD did not represent a public health problem for children living in socio-economically vulnerable municipalities in the South Region of Brazil, suggesting a new panorama of this nutritional deficiency even in regions of low socio-economic conditions in these three states. Thus, in view of the current nutritional transition scenario, it is necessary to continuously monitor and improve public policies related to vitamin A supplementation in the country.
Assuntos
Deficiência de Vitamina A , Feminino , Humanos , Criança , Deficiência de Vitamina A/epidemiologia , Vitamina A , Cidades , Brasil/epidemiologia , Estudos Transversais , Fatores de Risco , PrevalênciaRESUMO
People are exposed to pesticides through food, drinking water, and the environment. These compounds are associated with several disorders, such as inflammatory diseases, rheumatoid arthritis, cancer, and a condition related to metabolic syndrome. The immunotoxicants or immunotoxic compounds can cause a wide variety of effects on immune function, altering humoral immunity and cell-mediated immunity, resulting in adverse effects to the body. Here, immune system disorders are highlighted because they are closely linked to multiple organs, including the nervous, endocrine, reproductive, cardiovascular, and respiratory systems, leading to transient or permanent changes. Therefore, this study reviewed the mechanisms involved in the immunotoxicity of fungicides, herbicides, and insecticides in cells, animals, and humans in the past 11 years. According to the studies analyzed, the pesticides interfere with innate and adaptive immune functions, but the effects observed mainly on cellular and humoral immunity were highlighted. These compounds affected specific immune cells, causing apoptosis, changes in factor nuclear kappa B (NF-κB) expression, pro-inflammatory factors interleukin 6 (IL-6), interleukin 8 (IL-8), interferon-gamma (IFN-γ), chemokines (CXCL-c1c), and anti-inflammatory factor, such as interleukin 10 (IL-10). To verify the threats of these compounds, new evaluations with immunotoxicological biomarkers are necessary. HighlightsPesticides interfere with the innate and adaptive immune response.Cells, animals and human studies demonstrate the immunotoxicity of pesticides in the cellular and humoral immune response.Fungicides, herbicides, and insecticides alter the immune system by various mechanisms, such as pro-inflammatory and anti-inflammatory factors.
Assuntos
Praguicidas , Humanos , Praguicidas/toxicidade , Imunidade HumoralRESUMO
The discovery of a new drug requires over a billion dollars and around 12 years of research efforts, and toxicity is the leading reason for the failure to approve candidate drugs. Many alternative methods have been validated to detect toxicity as early as possible to diminish the waste of resources and efforts in medicinal chemistry research, and in vivo alternative methods are especially valuable for the amount of information they can provide at little cost and in a short time. In this work, we present a review of the literature published between the years 2000 and 2021 on in vivo alternative methods of toxicity screening employed in medicinal chemistry, which we believe will be useful because, in addition to shortening the research time, these studies provide much additional information aside from the toxicity of drug candidate compounds. These in vivo models include zebrafish, Artemia salina, Galleria mellonella, Drosophila melanogaster, planarians, and Caenorhabditis elegans. The most published ones in the last decade were zebrafish, D. melanogaster, and C. elegans due to their reliability, ease, and cost-effectiveness in implementation and flexibility. Special attention is given to C. elegans because of its rising popularity, a wide range of uses, including toxicity screening, and active effects measurement, from antioxidant effects to anthelmintic and antimicrobial activities, and its fast and reliable results. Over time, C. elegans also became a viable high-throughput (HTS) automated drug screening option. Additionally, this manuscript lists briefly the other screening methods used for the initial toxicological analyses and the role of alternative in vivo methods in these scenarios, classifying them as in silico, in vitro and alternative in vivo models that have been receiving a growing increase in interest in recent years.
Assuntos
Caenorhabditis elegans , Drosophila melanogaster , Animais , Antioxidantes/farmacologia , Descoberta de Drogas/métodos , Reprodutibilidade dos Testes , Peixe-ZebraRESUMO
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.
Assuntos
Exposição Ocupacional , Cromo/toxicidade , Cromo/urina , Ensaio Cometa , Humanos , Masculino , Metais , Exposição Ocupacional/efeitos adversos , Medição de RiscoRESUMO
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).
Assuntos
Antioxidantes , Arsênio , Adolescente , Agroquímicos , Antioxidantes/metabolismo , Butirilcolinesterase , Criança , Pré-Escolar , Cromo , Dano ao DNA , Glutationa Peroxidase , Humanos , Chumbo , Mucosa Bucal/metabolismo , Estresse Oxidativo , XenobióticosRESUMO
Peripheral biomarkers are important tools for detecting occupational exposures to prevent the onset and/or progression of diseases. Studies that reveal early peripheral biomarkers are highly important to preserve the health of workers and can potentially contribute to diagnosing and/or prognosing occupational pathologies. Exposure to crystalline silica is a problem in several workplaces because it increases the risk of chronic obstructive pulmonary disease (COPD), tuberculosis, cancer, and pulmonary fibrosis, clinically defined as silicosis. Silicosis is diagnosed by chest radiography and/or lung tomography in advanced stages when there is a severe loss of lung function. Peripheral biomarkers can help in diagnosing early changes prior to silicosis and represent a highly important technical-scientific advance that is minimally invasive. This review aimed to investigate the biomarkers studied for evaluating occupational exposure to crystalline silica and to understand the recent advances in this area. Potential oxidative, inflammatory, and immunological biomarkers were reviewed, as well as routine biomarkers such as biochemical parameters. It was found that biomarkers of effect such as serum CC16 and l-selectin levels could represent promising alternatives. Additionally, studies have shown that neopterin levels in urine and serum can be used to monitor worker exposure. However, further studies are needed that include a greater number of participants, different times of exposure to crystalline silica, and a combination of silicosis patients and healthy volunteers. Evaluating the concentration of crystalline silica in occupational environments, its impact on biomarkers of effect, and alterations in lung function could contribute to revealing early health alterations in workers in a more robust manner.
Assuntos
Biomarcadores/análise , Exposição Ocupacional/efeitos adversos , Fibrose Pulmonar/induzido quimicamente , Dióxido de Silício/efeitos adversos , Silicose/etiologia , Humanos , Dióxido de Silício/químicaRESUMO
Agriculture activities have increased the concentration of pesticides and metals in the environment. The excessive use of pesticides can generate an environmental impact and contribute to the development of human diseases. This study aimed to determine the presence of pesticides and metals in water samples collected in the Brazilian rural area in two different periods (before and after pesticide application) and to evaluate the alternative bioassays Lactuca sativa, Allium cepa, and Caenorhabditis elegans to monitoring toxicity in human drinking water samples. Eight sites in the rural area were selected and water samples were collected in two different periods of the year (before and after pesticide application). The presence of the pesticides was determinated by ultra-high performance liquid chromatography-tandem mass spectrometry and metals by inductively coupled plasma mass spectrometry. The potential toxicity of the water samples was performed with three different alternatives in vivo models (L. sativa, A. cepa, and C. elegans). Fifty-seven pesticides were analyzed and, according to the results, the most found ones were clomazone, atrazine, tebuconazole, metconazole, pyrimethanil, and carbofuran-3-hydroxide, which is a metabolic degradation product of insecticide carbofuran. The most detected metals were Cu, Cr, Mg, Fe, and Mn. The assays with L. sativa and A. cepa showed alterations in the period after pesticide application, while C. elegans presented changes in both periods compared to the same collection sites. These results indicate that bioassays, especially C. elegans, could be complementary and useful tools for monitoring the toxicity in drinking water samples.
RESUMO
INTRODUCTION: Our goal was to demonstrate the effects of occupational exposure to antineoplastic drugs on oxidative stress parameters and DNA damage in health professionals who manipulate and administer antineoplastic drugs in a University Hospital in Southern Brazil. METHODS: The case-control study with a longitudinal design, involved 64 individuals, 29 of them pharmacists, pharmacy technicians and nurses who were occupationally exposed to antineoplastic drugs and 35 professionals who were not exposed. Gene mutations were determined by micronucleus from salivary fluid; DNA damage by comet assay and oxidative stress parameters in whole blood were also evaluated. RESULTS: All workers exposed to antineoplastic drugs used personal protective equipment (PPE). It was demonstrated that the total nonprotein thiol and thiobarbituric acid reactive substances levels showed interaction between group and time, with higher levels one week after handling/administration of antineoplastic drugs in the exposed group (GEE, p ≤ 0.0001 and p = 0,013, respectively). Additionally, there was a group effect on the activities of the catalase and glutathione peroxidase antioxidant enzymes (GEE, p = 0.027 and p ≤ 0.0001, respectively), and workers occupationally exposed to antineoplastic drugs had higher enzyme activities compared to those not exposed. No genotoxic damage was demonstrated through the evaluated parameters. CONCLUSIONS: Despite the correct use of PPE, professionals occupationally exposed to antineoplastic drugs were more susceptible to oxidative stress than those not exposed. The evaluation of the studied parameters is especially important for the definition of conducts and practices in the area, always in search of guaranteeing the establishment of a rational policy to protect workers' health.
Assuntos
Antineoplásicos/efeitos adversos , Pessoal de Saúde , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Dano ao DNA , Hospitais Universitários , Humanos , Masculino , Equipamento de Proteção IndividualRESUMO
Arsenic (As) causes health effects, especially cancer. Rice (Oryza sativa L.) can contain high As concentrations. Using ICP-MS, we quantified the total As (tAs) levels in the main brands of rice (n = 103) and infant cereals (n = 27) consumed by Brazilians. The levels were compared to the maximum limits prescribed by regulatory agencies. We estimated the daily intake (EDI) of As by Brazilians by combining the mean As concentration determined in the white rice samples with per capita daily consumption divided by the average body weight as reported by the Brazilian Institute of Geography and Statistics in 2010. The possible health risk for consumers was assessed by calculating the margin of exposure (MOE) as prescribed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Moreover, tAs was determined in 11 pesticides used by Brazilian farmers. The tAs levels in the rice ranged from 0.003 to 1.3 mg kg-1. Approximately 27% of the white rice contained tAs levels above the limit set by Mercosul (0.3 mg kg-1) and 45% were above the limit set by the European Commission (0.2 mg kg-1). In the infant cereals, tAs levels ranged from 0.003 to 0.243 mg kg-1. In the pesticides, tAs levels ranged from 0.005 to 0.315 mg L-1. The EDI showed that, on average, Brazilians consume 4.13 µg As kg-1 BW weekly. In addition, a low MOE was observed, demonstrating that high use of rice presents a risk of high inorganic (iAs) exposure, which represents a public health concern.
Assuntos
Arsenicais/análise , Contaminação de Alimentos/análise , Alimentos Infantis/análise , Oryza/química , Adolescente , Adulto , Idoso , Brasil , Grão Comestível/química , Exposição Ambiental/análise , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Praguicidas/química , Medição de Risco , Adulto JovemRESUMO
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/análiseRESUMO
Fish consumption and chronic exposure to low doses of mercury (Hg) seems to activate several molecular mechanisms leading to carcinogenic and/or teratogenic processes. However, Hg genotoxic effects on humans are not completely described. In the present study, we assessed cytogenetic damage in isolated human peripheral lymphocytes using the cytokinesis-block micronucleus cytome assay (CBMN-Cyt), micronucleus formation with anti-kinetochore antibody (CREST staining), levels of total Hg in hair (T-Hg), fish consumption, and estimated Hg dose. The study comprised 39 non-exposed, and 73 residents from La Mojana region, an area with a well-documented Hg contamination. Data showed a significant increase in micronuclei (MNBN), nucleoplasmic bridges (NPB), and necrotic and apoptotic cell frequencies in residents of "La Mojana." The overall mean T-Hg level in hair for exposed residents was 1.12 ± 0.94 mg kg-1 and 0.15 ± 0.05 in individuals from the reference area. Approximately 40% of analyzed individuals showed T-Hg levels that exceeded US Environmental Protection Agency (USEPA) reference dose. Increased T-Hg levels in hair were related to increased MNBN frequencies and high fish consumption. Other cellular markers, such as necrotic and apoptotic cell frequencies, were also correlated with high fish intake and T-Hg contents. Results of the CREST staining demonstrated that in vivo exposure to Hg induces genetic instability by chromosome fragment loss (clastogenic). Additionally, a high average intake of some fish species, particularly with carnivorous habits like Caquetaia kraussii, Hoplias malabaricus, and Sorubin cuspicaudus, seems to increase MNBN frequencies significantly.
Assuntos
Mercúrio , Animais , Colômbia , Análise Citogenética , Exposição Dietética , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Peixes , Humanos , Mercúrio/análise , Mercúrio/toxicidadeRESUMO
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.
Assuntos
Antioxidantes/farmacologia , Ocratoxinas/farmacologia , Vitis/química , Vinho/análise , Antioxidantes/análise , Catalase/genética , Catalase/metabolismo , Cromatografia Líquida , Ocratoxinas/análise , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Espectrometria de Massas em TandemRESUMO
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.
Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Amaryllidaceae/química , Antiprotozoários/farmacologia , Neutrófilos/metabolismo , Nucleosídeo-Trifosfatase/antagonistas & inibidores , Fenantridinas/farmacologia , Extratos Vegetais/farmacologia , Proteínas de Protozoários/antagonistas & inibidores , Tricomoníase/metabolismo , Trichomonas vaginalis/enzimologia , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/metabolismo , Humanos , Neutrófilos/efeitos dos fármacos , Nucleosídeo-Trifosfatase/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tricomoníase/parasitologia , Trichomonas vaginalis/efeitos dos fármacos , Trichomonas vaginalis/crescimento & desenvolvimento , Trichomonas vaginalis/metabolismo , Trofozoítos/efeitos dos fármacos , Trofozoítos/enzimologia , Trofozoítos/crescimento & desenvolvimento , Trofozoítos/metabolismoRESUMO
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.