RESUMO
This study evaluated the median lethal concentration of silver nanoparticles and their effects in fish tambaqui Colossoma macropomum. Therefore, an acute toxicity assay was carried out in completely randomized design evaluating six different concentrations of silver nanoparticles on blood parameters of tambaqui. The silver nanoparticles were produced by chemical reduction with polyvinyl alcohol (AgNP-PVA). The lethal concentration 50% (LC50) was estimated using probit regression. The blood was collected, analyzed and the data were submitted to T-test (dying x surviving fish) and Tukey test (surviving fish). An increase in glucose, hematocrit, total plasma protein, hemoglobin, erythrocytes, leukocytes, monocytes, and neutrophils as well as reduced MCV (mean corpuscular volume) in dying fish compared to surviving fish were observed. Survived fish exposed to 187.5 µg/L showed an increase in hematocrit, MCV, and MCH and a reduction in erythrocytes, total numbers of leukocyte, thrombocyte, lymphocyte, and neutrophil. The fish exposed to concentrations below 125 µg/L, had returned the blood parameter to baselines compared to control. The estimated LC50 was 165.09 µg/L and was classified as highly toxic for the fish tambaqui. In higher concentrations, it causes an acute respiratory toxicity, but in concentrations below 125 µg/L, the fish can adapt to the stressing agent.
Assuntos
Caraciformes , Nanopartículas Metálicas , Animais , Prata/toxicidade , Nanopartículas Metálicas/toxicidade , Células Sanguíneas , EritrócitosRESUMO
In aquaculture conditions, severe parasitic infections cause negative impacts on fish health and economic losses. The parasite load has been associated with anemia, which reduces the number of erythrocytes in fish. Therefore, the evaluation of hematological parameters as a feasible tool for diagnosing and monitoring fish health allows us to determine the indirect effect of parasites on the health status of fish. Our aim was to evaluate changes in the blood cell parameters of Lagocephalus laevigatus associated with parasitism. A total of 99 puffer fish were collected from the coast of Seybaplaya, Campeche. Each fish had 20 µl of peripheral blood drawn, and blood smears were performed in triplicate. The smears were stained with Giemsa stain, and a quantitative analysis of blood cells (erythrocytes, leukocytes, and monocytes) was obtained with an optical microscope at 100 ×. The parasites recovered from each fish were fixed and identified, and the infection parameters were calculated. Through generalized additive model analysis (GAMLSS), we observed that the infection intensity of puffer fish influenced changes in hematological parameters, principally in erythrocytes, neutrophils, thrombocytes, the total fish length, and the condition factor of the fish. In conclusion, this is the first study that provides baseline data on the hematological parameter variations in uninfected and infected L. laevigatus, the tropical wild puffer fish, as well as the possible effects on fish health. It is necessary to establish reference hematological patterns in wild populations for diagnosis and timely management with emphasis on aquaculture fish.
Assuntos
Tetraodontiformes , Animais , México , Células Sanguíneas , Eritrócitos , LeucócitosRESUMO
The evidence supporting the biological plausibility of the association of permethrin and malathion with hematological cancer is limited and contradictory; thus, further studies are needed. This study aimed to investigate whether in vitro exposure to 0.1 µM permethrin and malathion at 0, 24, 48 and 72 h after cell culture initiation induced changes in the gene expression and DNA methylation in mononuclear cells from bone marrow and peripheral blood (BMMCs, PBMCs). Both pesticides induced several gene expression modifications in both tissues. Through gene ontology analysis, we found that permethrin deregulates ion channels in PBMCs and BMMCs and that malathion alters genes coding proteins with nucleic acid binding capacity, which was also observed in PBMCs exposed to permethrin. Additionally, we found that both insecticides deregulate genes coding proteins with chemotaxis functions, ion channels, and cytokines. Several genes deregulated in this study are potentially associated with cancer onset and development, and some of them have been reported to be deregulated in hematological cancer. We found that permethrin does not induce DNA hypermethylation but can induce hypomethylation, and that malathion generated both types of events. Our results suggest that these pesticides have the potential to modify gene expression through changes in promoter DNA methylation and potentially through other mechanisms that should be investigated.
Assuntos
Células da Medula Óssea , Metilação de DNA , Expressão Gênica , Inseticidas , Malation , Organofosfatos , Permetrina , Expressão Gênica/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Permetrina/toxicidade , Malation/toxicidade , Inseticidas/toxicidade , Organofosfatos/toxicidade , Células da Medula Óssea/efeitos dos fármacos , Células Sanguíneas/efeitos dos fármacos , Humanos , Masculino , Adulto Jovem , Células CultivadasRESUMO
Introduction: Epigenetic marks have been proposed as early changes, at the subcellular level, in disease development. To find more specific biomarkers of effect in occupational exposures to toxicants, DNA methylation studies in peripheral blood cells have been performed. The goal of this review is to summarize and contrast findings about DNA methylation in blood cells from workers exposed to toxicants. Methods: A literature search was performed using PubMed and Web of Science. After first screening, we discarded all studies performed in vitro and in experimental animals, as well as those performed in other cell types other than peripheral blood cells. Results: 116 original research papers met the established criteria, published from 2007 to 2022. The most frequent investigated exposures/labor group were for benzene (18.9%) polycyclic aromatic hydrocarbons (15.5%), particulate matter (10.3%), lead (8.6%), pesticides (7.7%), radiation (4.3%), volatile organic compound mixtures (4.3%), welding fumes (3.4%) chromium (2.5%), toluene (2.5%), firefighters (2.5%), coal (1.7%), hairdressers (1.7%), nanoparticles (1.7%), vinyl chloride (1.7%), and others. Few longitudinal studies have been performed, as well as few of them have explored mitochondrial DNA methylation. Methylation platforms have evolved from analysis in repetitive elements (global methylation), gene-specific promoter methylation, to epigenome-wide studies. The most reported observations were global hypomethylation as well as promoter hypermethylation in exposed groups compared to controls, while methylation at DNA repair/oncogenes genes were the most studied; studies from genome-wide studies detect differentially methylated regions, which could be either hypo or hypermethylated. Discussion: Some evidence from longitudinal studies suggest that modifications observed in cross-sectional designs may be transitory; then, we cannot say that DNA methylation changes are predictive of disease development due to those exposures. Conclusion: Due to the heterogeneity in the genes studied, and scarcity of longitudinal studies, we are far away from considering DNA methylation changes as biomarkers of effect in occupational exposures, and nor can we establish a clear functional or pathological correlate for those epigenetic modifications associated with the studied exposures.
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Metilação de DNA , Epigênese Genética , Estudos Transversais , Biomarcadores , Células SanguíneasRESUMO
There is considerable controversy regarding the genotoxicity of glyphosate (N-(phosphonomethyl) glycine). It has been suggested that the genotoxicity of this herbicide is increased by the adjuvants added to commercial formulations based on glyphosate. The effect of various concentrations of glyphosate and three commercial glyphosate-based herbicides (GBH) on human lymphocytes was evaluated. Human blood cells were exposed to glyphosates of 0.1, 1, 10 and 50 mM as well as to equivalent concentrations of glyphosate on commercial formulations. Genetic damage (p < 0.05) was observed in all concentrations with glyphosate and with FAENA and TACKLE formulations. These two commercial formulations showed genotoxicity that was concentration-dependent but in a higher proportion compared to pure glyphosate only. Higher glyphosate concentrations increased the frequency and range of tail lengths of some migration groups, and the same was observed for FAENA and TACKLE, while in CENTELLA the migration range decreased but the frequency of migration groups increased. We show that pure glyphosate and commercial GBH (FAENA, TACKLE and CENTELLA) gave signals of genotoxicity in human blood samples in the comet assay. The genotoxicity increased in the formulations, indicating genotoxic activity also in the added adjuvants present in these products. The use of the MG parameter allowed us to detect a certain type of genetic damage associated with different formulations.
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Herbicidas , Humanos , Ensaio Cometa , Células Sanguíneas , Glicina , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos , GlifosatoRESUMO
Aim: This study investigated the influence of antidepressant drugs on methylation status of KCNE1, KCNH2 and SCN5A promoters and ECG parameters in adult psychiatric patients. Materials & methods: Electrocardiographic evaluation (24 h) and blood samples were obtained from 34 psychiatric patients before and after 30 days of antidepressant therapy. Methylation of promoter CpG sites of KCNE1, KCNH2 and SCN5A was analyzed by pyrosequencing. Results: Three CpG and four CpG sites of KCNE1 and SCN5A, respectively, had increased % methylation after treatment. Principal component analysis showed correlations of the methylation status with electrocardiographic variables, antidepressant doses and patient age. Conclusion: Short-term treatment with antidepressant drugs increase DNA methylation in KCNE1 and SCN5A promoters, which may induce ECG alterations in psychiatric patients.
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Antidepressivos , Metilação de DNA , Adulto , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Células Sanguíneas , Ilhas de CpG , Humanos , Canais Iônicos , Regiões Promotoras GenéticasRESUMO
ABSTRACT AIM: This study investigated the influence of antidepressant drugs on methylation status of KCNE1, KCNH2 and SCN5A promoters and ECG parameters in adult psychiatric patients. MATERIALS & METHODS: Electrocardiographic evaluation (24 h) and blood samples were obtained from 34 psychiatric patients before and after 30 days of antidepressant therapy. Methylation of promoter CpG sites of KCNE1, KCNH2 and SCN5A was analyzed by pyrosequencing. RESULTS: Three CpG and four CpG sites of KCNE1 and SCN5A, respectively, had increased % methylation after treatment. Principal component analysis showed correlations of the methylation status with electrocardiographic variables, antidepressant doses and patient age. CONCLUSION: Short-term treatment with antidepressant drugs increase DNA methylation in KCNE1 and SCN5A promoters, which may induce ECG alterations in psychiatric patients.
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Humanos , Adulto , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia , Células Sanguíneas , Regiões Promotoras Genéticas/genética , Ilhas de CpG , Metilação de DNA , Canais IônicosRESUMO
Benzophenone-3 (BP-3) is a common component of organic sunscreen widely used that can affect especially aquatic ecosystems health, including fish. To verify the biological effects of low concentrations of BP-3 on blood cells, one hundred and forty zebrafish (D. rerio) were used and then randomly divided into five groups: control group (water), solvent group (alcoholic water), and BP-3 group (BP-3 at 7 µg L-1, BP-3 at 70 µg L-1, and BP-3 at 700 µg L-1). The blood slices were stained with Panoptic stain and with Giemsa solution for the hematological analysis. During the exposure to BP-3, no behavioral changes were observed. Although no significant difference in total leukocytes occurred, an increase in neutrophils and a reduction of lymphocytes at the highest concentration on both 7th and 14th days were detected. The total and cytoplasmic area of erythrocytes on the 7th day at the highest concentration were reduced. In addition, alterations on the erythrocyte nuclear morphology in fish exposed to BP-3 were usually visualized, mainly when considered the occurrence of blebbed nucleus and micronucleus, indicating that BP-3 exhibits cytotoxic and mutagenic effects. The results indicate that BP-3 can interfere with the morphophysiology of aquatic organisms.
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Benzofenonas , Células Sanguíneas , Poluentes Químicos da Água , Peixe-Zebra , Animais , Benzofenonas/toxicidade , Células Sanguíneas/patologia , Ecossistema , Poluentes Químicos da Água/toxicidadeRESUMO
Introduction: Apical periodontitis (AP) is a common oral disease caused by the inflammatory destruction of the periapical tissues due to the infection of the root canal system of the tooth. It also contributes to systemic bacterial translocation, where peripheric mononuclear blood cells (PBMCs) can act as carriers. Toll-like receptor (TLR) 2 mediates the response to infection and activates inflammatory responses. DNA methylation can be induced by bacteria and contributes to the modulation of this response. Despite the evidence that supports the participation of PBMCs in immune-inflammatory disorders, the inflammatory profile and epigenetic regulatory mechanisms of PBMCs in AP individuals are unknown. Aim: To determine TLR2 gene methylation and inflammatory profiles of PBMCs in AP. Methods: Cross-sectional exploratory study. Otherwise, healthy individuals with AP (n=27) and controls (n=30) were included. PMBCs were isolated by a Ficoll gradient, cultured for 24 hours, and both RNA and DNA were extracted. DNA was bisulfite-treated, and specific sites at the promoter region of the TLR2 gene were amplified by qPCR using validated primers. To verify its amplification, agarose gels were performed. Then, the PCR product was sequenced. mRNA expression of TLR2 was determined by qPCR. The soluble levels of 105 inflammatory mediators were first explored with Proteome Profiler Human Cytokine Array Kit. Consequently, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-6Rα, IL-1ß, and IL-12p70 levels were measured by Multiplex assay. Results: PBMCs from individuals with AP demonstrated a proinflammatory profile showing higher soluble levels of TNF-α, IL-6, and IL-1ß compared to controls (p<0.05). Higher TLR2 expression and higher global methylation pattern of the promoter region of the gene were found in AP compared to controls (p<0.05). The CpGs single-sites at positions -166 and -146 were completely methylated, while the site -102 was totally unmethylated, independently of the presence of AP. DNA methylation of CpG single-sites in positions -77 and +24 was positively associated with TLR2 expression. Conclusions: PBMCs from AP subjects show a hyperinflammatory phenotype and TLR2 upregulation in association with single CpG-sites' methylation from the TLR2 gene promoter, thereby contributing to a sustained systemic inflammatory load in individuals with periapical endodontic diseases.
Assuntos
Periodontite Periapical , Receptor 2 Toll-Like , Células Sanguíneas/metabolismo , Estudos Transversais , Metilação de DNA , Humanos , Interleucina-6/metabolismo , Periodontite Periapical/genética , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Gene expression can be modified in people who are chronically exposed to high concentrations of heavy metals. The soil surrounding the Ventanas Industrial Complex, located on the coastal zone of Puchuncaví and Quintero townships (Chile), contain heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed international standards. The aim of this study was to determine the potential association of the heavy metals in soils, especially arsenic, with the status of methylation of four tumor suppressor genes in permanent residents in those townships. To study the methylation status in genes p53, p16, APC, and RASSF1A, we took blood samples from adults living in areas near the industrial complex for at least 5 years and compared it to blood samples from adults living in areas with normal heavy metal concentrations of soils. Results indicated that inhabitants of an area with high levels of heavy metals in soil have a significantly higher proportion of methylation in the promoter region of the p53 tumor suppressor gene compared with control areas (p-value: 0.0035). This is the first study to consider associations between heavy metal exposure in humans and aberrant DNA methylation in Chile. Our results suggest more research to support consistent decision-making on processes of environmental remediation or prevention of exposure.