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1.
Braz. j. biol ; 84: e251289, 2024. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1355889

ABSTRACT

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.


Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.


Subject(s)
Animals , Rabbits , DNA Damage , Antineoplastic Agents , Micronucleus Tests , Dose-Response Relationship, Drug , Erythrocytes , Venlafaxine Hydrochloride/toxicity
2.
Braz. j. biol ; 83: e251198, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1339350

ABSTRACT

Abstract The present study was designed to investigate the effects of Gundelia tournefortii L. plant extract on different tissues in terms of DNA damage, biochemical and antioxidant parameter values in rats with high-calorie diets. With this aim, Wistar albino male rats were divided into 4 groups containing 6 rats each and the study was completed over 12 weeks duration. At the end of the implementation process over the 12 weeks, rats were sacrificed and blood and tissue samples were obtained. Analyses were performed on blood and tissue samples. According to results for DNA damage (8-OHdG), in brain tissue the OG2 group was significantly reduced compared to the NC group. For MDA results in liver tissue, OG1 and OG2 groups were determined to increase by a significant degree compared to the control group, while the OG2 group was also increased significantly compared to the obese group. In terms of the other parameters, comparison between the groups linked to consumption of a high calorie diet (HCD) and administration of Gundelia tournefortii L. in terms of antioxidant activities and serum samples obtained statistically significant results. Gundelia tournefortii L. plant extracts had effects that may be counted as positive on antioxidant parameter activity and were especially identified to improve DNA damage and MDA levels in brain tissues. Additionally, consumption of Gundelia tournefortii L. plant extract in the diet may have antiobesity effects; thus, it should be evaluated for use as an effective weight-loss method and as a new therapeutic agent targeting obesity.


Resumo O presente estudo foi desenhado para investigar os efeitos do extrato da planta Gundelia tournefortii L. em diferentes tecidos em termos de danos ao DNA, valores de parâmetros bioquímicos e antioxidantes em ratos com dietas hipercalóricas. Com esse objetivo, ratos Wistar albinos machos foram divididos em 4 grupos contendo 6 ratos cada e o estudo foi concluído ao longo de 12 semanas de duração. No final desse processo de implementação, os ratos foram sacrificados e amostras de sangue e tecido foram obtidas. As análises foram realizadas em amostras de sangue e tecido. De acordo com os resultados para danos ao DNA (8-OHdG), no tecido cerebral o grupo OG2 foi significativamente reduzido em comparação com o grupo NC. Para os resultados de MDA no tecido hepático, os grupos OG1 e OG2 aumentaram significativamente em comparação ao grupo controle, enquanto o grupo OG2 também aumentou significativamente em comparação ao grupo obeso. Quanto aos demais parâmetros, a comparação entre os grupos ligados ao consumo de dieta hipercalórica (DC) e à administração de Gundelia tournefortii L. em termos de atividades antioxidantes e amostras de soro obteve resultados estatisticamente significativos. Os extratos de plantas de Gundelia tournefortii L. tiveram efeitos que podem ser considerados positivos na atividade dos parâmetros antioxidantes e foram especialmente identificados para melhorar os danos ao DNA e os níveis de MDA nos tecidos cerebrais. Além disso, o consumo de extrato vegetal de Gundelia tournefortii L. na dieta pode ter efeitos antiobesidade; portanto, deve ser avaliado para uso como um método eficaz de perda de peso e como um novo agente terapêutico voltado para a obesidade.


Subject(s)
Animals , Rats , Asteraceae , Antioxidants , DNA Damage , Plant Extracts/pharmacology , Rats, Wistar , Obesity/drug therapy
3.
Braz. j. biol ; 83: e240118, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1278559

ABSTRACT

Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.


Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados ​​contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.


Subject(s)
Humans , Animals , Zika Virus , Zika Virus Infection , Insecticides/toxicity , DNA Damage , Chromosome Aberrations , Plant Roots , Onions , Mosquito Vectors , Malathion/toxicity , Mitotic Index
4.
Braz. j. biol ; 83: e243910, 2023. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1278525

ABSTRACT

Abstract Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.


Resumo O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T.cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.


Subject(s)
Humans , Animals , Trypanosoma cruzi/genetics , Xeroderma Pigmentosum , DNA Damage/genetics , Computational Biology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , DNA Repair/genetics
5.
Braz. j. biol ; 82: e243628, 2022. tab, graf
Article in English | LILACS | ID: biblio-1249260

ABSTRACT

Abstract Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.


Resumo Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.


Subject(s)
Chocolate , Mutagens/toxicity , DNA Damage , Brazil , Plant Roots , Onions , Food Additives
6.
Braz. j. biol ; 81(2): 268-277, 2021. tab, graf
Article in English | MEDLINE, LILACS, VETINDEX | ID: biblio-1153357

ABSTRACT

This study evaluated the genotoxicity of lyophilized glycolic extract of Theobroma cacao Linné seeds (TCL), using the micronucleus assay in bone marrow of mice. The interaction between TCL and doxorubicin (DXR) was also analyzed. Experimental groups were evaluated 24-48 h after treatment with N-Nitroso-N-ethylurea (NEU: 50 mg/kg), DXR (5 mg/kg), NaCl (145 mM), TCL (0.5-2 g/kg), and TCL (2 g/kg) in combination with DXR (antigenotoxic assays). Analysis of micronucleated polychromatic erythrocytes (MNPCEs) showed no significant differences between all the treatment doses of TCL and NaCl control. Mice experimentally treated with DXR and NEU significantly induced MNPCEs. However, a significant reduction of MNPCEs was also observed when TCL was administered in combination with the chemotherapeutic agent DXR. The analysis of the PCE/NCE ratio revealed no significant differences between the NaCl control, all doses of TCL, and DXR. However, there were significant differences in the PCE/NCE ratio between positive NEU control and all other treatments. The PCE/NCE ratio observed after treatment with TCL and DXR showed significant differences and intermediate values to controls (NaCl and NEU). This study suggests absence of genotoxicity and cytotoxicity of TCL, regardless of dose, sex, and time. TCL reduced genotoxic effects induced by DXR, suggesting potential antigenotoxic effects.


Este estudo avaliou a genotoxicidade do extrato glicólico liofilizado de sementes de Theobroma cacao Linné (TCL), usando o ensaio do micronúcleo em medula óssea de camundongos. A interação entre TCL e doxorrubicina (DXR) foi também analisada. Grupos experimentais foram avaliados 24-48 h após tratamento com N-Nitroso-N-etilureia (NEU: 50 mg/kg), DXR (5 mg/kg), NaCl (145 mM), TCL (0,5-2 g/kg), e TCL (2 g/kg) em combinação com DXR (ensaio antigenotóxico). As análises de eritrócitos policromáticos micronucleados (EPCMNs) não mostraram diferenças significantes entre todas as doses de tratamento do TCL e o controle NaCl. Camundongos experimentalmente tratados com DXR e NEU induziram significativamente EPCMNs. Contudo, uma redução significante de EPCMNs foi também observada quando TCL foi administrada em combinação com o agente quimioterapêutico DXR. As análises da relação EPC/ENC (eritrócito policromático/eritrócito normocromático) revelaram ausência de diferenças significantes entre o controle NaCl, todas as doses de TCL e DXR. Contudo, houve diferenças significantes na relação EPC/ENC entre o controle positivo NEU e todos os outros tratamento. A relação ECP/ENC observada após o tratamento com TCL e DXR mostrou diferenças significantes e valores intermediários aos controles (NaCl e NEU). Este estudo sugere ausência de genotoxicidade e citotoxicidade de TCL, independentemente da dose, sexo e tempo. TCL reduziu os efeitos genotóxicos induzidos por DXR, sugerindo potencial efeitos antigenotóxicos.


Subject(s)
Animals , Mice , DNA Damage , Cacao/toxicity , Cytotoxins/analysis , Plant Extracts/pharmacology , Micronucleus Tests , Doxorubicin , Erythrocytes
7.
Bol. latinoam. Caribe plantas med. aromát ; 20(2): 101-122, 2021. ilus, tab
Article in English | LILACS | ID: biblio-1342191

ABSTRACT

Humans when exposed to harmful ionising radiations suffer from various pathophysiological disorders including cancer. Radiotherapy is a treatment where these cancerous cells within a tumor aretargeted and killed by means of high energy waves. This therapy is very expensive and involves highly sophisticated instruments. In addition to this, most synthetic radioprotectors including Amifostine have been found to possess toxicity. This led researchers to develop a novel, economically viable, and efficient therapeutic alternative to radiation therapy. The last two decades have observed a major shift towards investigating natural products as radioprotectors, as these are immensely effective in terms of their potential bioequivalence relative to many of the established synthetic compounds available. Taking into account the limitations of radiation therapy, an approach 'Integrative Oncology' that involves a combination of both traditional and conventional medical treatment are used nowadays to treat patients suffering from cancer and associated mental and psychological disorders.


Los seres humanos, cuando se exponen a radiaciones ionizantes nocivas, sufren diversos trastornos fisiopatológicos, incluido el cáncer. La radioterapia es un tratamiento en el que estas células cancerosas dentro de un tumor son atacadas y destruidas por medio de ondas de alta energía. Esta terapia es muy cara e implica instrumentos muy sofisticados. Además de esto, se ha descubierto que la mayoría de los radioprotectores sintéticos, incluida la amifostina, poseen toxicidad. Esto llevó a los investigadores a desarrollar una novedosa, económicamente viable y eficiente alternativa terapéutica a la radioterapia. En las dos últimas décadas se ha observado un cambio importante hacia la investigación de productos naturales como radioprotectores, ya que son inmensamente eficaces en términos de su potencial bioequivalencia en relación con muchos de los compuestos sintéticos establecidos disponibles. Teniendo en cuenta las limitaciones de la radioterapia, hoy en día se utiliza un enfoque de "Oncología Integrativa" que implica una combinación de tratamiento médico tradicional y convencional para tratar a pacientes que padecen cáncer y trastornos mentales y psicológicos asociados.


Subject(s)
Humans , Plants/chemistry , Radiation-Protective Agents , Biological Products , Integrative Oncology/methods , Radiotherapy/methods , DNA Damage , Radiation Oncology/methods , Genomic Instability
8.
Braz. arch. biol. technol ; 64: e21200093, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153294

ABSTRACT

HIGHLIGHTS Sodium arsenite can cause neoplastic transformation in cells. Curcumin reduced cell viability and increased LDH activity in transformed Balb/c 3T3 cells. Curcumin caused DNA damage in transformed Balb/c 3T3 cells. Curcumin may play a protective role in sodium arsenite-induced toxicity.


Abstract Arsenic is a toxic substance that spreads widely around the environment and accumulates as metalloid in the earth's crust. Arsenic and its derivatives are found in drinking water, nutrients, soil, and air. Exposure to arsenic is associated with lung, blood, skin cancer and various lesions. Curcumin is a polyphenolic compound derived from Curcuma longa (turmeric) rhizome and is one of the main curcuminoids. Curcumin is known to be antioxidant, antibacterial, anti-inflammatory, analgesic effects. This study aimed to investigate the potential of sodium arsenite to transform embryonic fibroblast cells and to evaluate the cytotoxic and genotoxic effects of curcumin in neoplastic transformed cells. Neoplastic cells transformation was induced by sodium arsenite in Balb/c 3T3 cells at the end of 32 days. After transformation assay, the transformed cells were treated with various concentration of curcumin to evaluate cell viability, lactate dehydrogenase activity and DNA damage for 24h. The results revealed that curcumin decreased cell viability and increased the activity of lactate dehydrogenase enzyme in neoplastic transformed Balb/c 3T3 cells. In conclusion, the results demonstrated that curcumin has an anticancer effect on neoplastic transformed Balb/c 3T3 cells by causing DNA damage.


Subject(s)
Animals , Mice , Arsenic/toxicity , DNA Damage , Cell Transformation, Neoplastic , Curcumin/pharmacology , Fibroblasts/drug effects , BALB 3T3 Cells , Fibroblasts/pathology
9.
Rev. epidemiol. controle infecç ; 10(3): [1-11], jul.-set. 2020. ilus
Article in Portuguese | LILACS | ID: biblio-1224105

ABSTRACT

Justificativa e Objetivos: A Unidade de Terapia Intensiva (UTI) é responsável pelo tratamento de pacientes críticos e sua monitorização contínua pode melhorar a qualidade dos cuidados prestados. O objetivo deste estudo é associar a Escala Psicológica Aguda Simplificada (SAPS 3) com os níveis inflamatórios e o dano ao DNA em pacientes internados na UTI de um hospital do Vale do Taquari, Rio Grande do Sul, Brasil. Métodos: Trata-se de uma pesquisa transversal realizada com 22 pacientes internados em uma UTI adulta, no período de janeiro a junho de 2016. O escore SAPS 3 foi pontuado pela equipe médica na admissão dos pacientes e amostras sanguíneas foram obtidas após 24 e 72 horas de internação para dosagem de Proteína C Reativa (PCR) e dano no DNA. Resultados: O escore SAPS 3 não se associou ao PCR de 24 e 72h. Entretanto, o escore SAPS 3 associou-se significativamente ao índice e a frequência de dano DNA, somente após 72 horas de internação. Conclusão: O escore de gravidade não se associou aos níveis de PCR, mas a danos no DNA, somente após 72 horas da admissão.(AU)


Background and Objectives: The Intensive Care Unit (ICU) is responsible for the treatment of critical patients and monitoring it continuously can improve the quality of care provided. This study aims to associate the Simplified Acute Physiology Score (SAPS 3) with inflammatory levels and genomic damage in patients admitted to the ICU of a hospital in Vale do Taquari, Rio Grande do Sul, Brazil. Methods: This is a cross-sectional study conducted with 22 patients from an adult ICU, between January and June 2016. The SAPS 3 was scored by the medical staff at the admission of patients and blood samples were obtained after 24 and 72 hours of hospitalization for C-Reactive Protein (CRP) dosing and DNA damage. Results: The SAPS 3 score was not associated with 24- and 72-hours CRP. However, the SAPS 3 score was significantly associated with the index and frequency of DNA damage, only after 72 hours of hospitalization. Conclusion: The severity score was not associated with CRP levels, but with DNA damage only after 72 hours of admission.


Justificación y objetivos: La Unidad de Cuidados Intensivos (UCI) es responsable del tratamiento de pacientes críticos, y su monitoreo continuo puede mejorar la calidad de la atención ofrecida. El presente estudio tuvo como objetivo asociar la Puntuación Fisiológica Simplificada Aguda (SAPS 3) con los niveles inflamatorios y el daño al ADN en pacientes de la UCI de un hospital del Valle de Taquari, Rio Grande do Sul, Brasil. Métodos: Este es un estudio transversal realizado con 22 pacientes ingresados en una UCI de adultos, entre enero y junio de 2016. El equipo médico calificó la puntuación SAPS 3 al ingreso de los pacientes, y se obtuvieron muestras de sangre después de 24 y 72 h de hospitalización para la medición del PCR y el daño al ADN. Resultados: La puntuación SAPS 3 no se asoció con la Proteína C Reactiva (PCR) a 24 y 72 horas. Sin embargo, lo asoció significativamente con el índice y la frecuencia de daño al ADN solo después de 72 horas de hospitalización. Conclusiones: El puntaje de gravedad no se asoció con los niveles de PCR, sino con el daño al ADN solamente 72 horas después del ingreso de los pacientes.(AU)


Subject(s)
Humans , DNA Damage , Polymerase Chain Reaction , Critical Care , Simplified Acute Physiology Score , Intensive Care Units
10.
An. bras. dermatol ; 95(3): 314-319, May-June 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1130868

ABSTRACT

Abstract Background: Although not fully understood, oxidative stress has been implicated in the pathogenesis of different autoimmune diseases such as systemic sclerosis. Accumulating evidence indicates that oxidative stress can induce mitochondrial DNA (mtDNA) damage and variations in mtDNA copy number (mtDNAcn). Objective: The aim of this study was to explore mtDNAcn and oxidative DNA damage byproducts in peripheral blood of patients with systemic sclerosis and healthy controls. Methods: Forty six patients with systemic sclerosis and forty nine healthy subjects were studied. Quantitative real-time PCR used to measure the relative mtDNAcn and the oxidative damage (oxidized purines) of each sample. Results: The mean mtDNAcn was lower in patients with systemic sclerosis than in healthy controls whereas the degree of mtDNA damage was significantly higher in cases as compared to controls. Moreover, there was a negative correlation between mtDNAcn and oxidative DNA damage. Study limitations: The lack of simultaneous analysis and quantification of DNA oxidative damage markers in serum or urine of patients with systemic sclerosis and healthy controls. Conclusion: These data suggest that alteration in mtDNAcn and increased oxidative DNA damage may be involved in the pathogenesis of systemic sclerosis.


Subject(s)
Humans , Male , Female , Adult , Scleroderma, Systemic/genetics , Scleroderma, Systemic/blood , DNA Damage , DNA, Mitochondrial/genetics , DNA, Mitochondrial/blood , Oxidative Stress/genetics , DNA Copy Number Variations , Reference Values , Case-Control Studies , Reactive Oxygen Species/blood , Statistics, Nonparametric , Electrophoresis, Agar Gel , Real-Time Polymerase Chain Reaction , Middle Aged
12.
Arq. bras. cardiol ; 114(2): 234-242, Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088869

ABSTRACT

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.


Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.


Subject(s)
Animals , Male , DNA Damage/genetics , Heart Failure/genetics , Reference Values , Rats, Wistar , Oxidative Stress , Muscle, Skeletal/pathology , Comet Assay , Single-Cell Analysis , Heart Failure/pathology , Heart Ventricles/pathology , Hemodynamics , Liver/pathology , Lung/pathology , Myocardial Infarction/genetics , Myocardial Infarction/pathology
13.
Article in Chinese | WPRIM | ID: wpr-826336

ABSTRACT

To explore the molecular mechanism of human papillomavirus subtype 16(HPV-16)E7 oncogene-induced DNA re-replication in response to DNA damage. Flow cytometry was performed to examine the cell cycle changes in RPE1 E7 cells stably expressing HPV-16 E7 and its control cell RPE1 Vector after DNA damage.Immunoblotting assay was used to evaluate the early mitotic inhibitor 1(Emi1)expression in RPE1 E7 and RPE1 Vector cells with or without DNA damage.The changes of the proportion of polyploidy was detected by flow cytometry in DNA-damaged RPE1 E7 cells interfered by Emi1 small interfering RNA. Compared with the control cells,the proportion of polyploids in RPE1 E7 cells was significantly increased in response to DNA damage(=6.397,=0.0031).Emi1 protein expression was significantly increased in DNA damaged RPE1 E7 cells(=8.241,=0.0012).The polyploid ratio of RPE1 E7 cells was significantly reduced after Emi1 was interfered by two independent small interfering RNAs(=2.916,=0.0434;=3.452,=0.0260). In response to DNA damage,Emi1 promoted DNA re-replication caused by HPV-16 E7.


Subject(s)
DNA Damage , DNA Replication , Human papillomavirus 16 , Mitosis , Oncogene Proteins, Viral
14.
Rev. Soc. Bras. Med. Trop ; 53: e20200467, 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS, SES-SP | ID: biblio-1143874

ABSTRACT

Abstract INTRODUCTION: Semi-synthetic dillapiole compounds derived from Piper aduncum essential oil are used as alternative insecticides to control insecticide-resistant Aedes aegypti. Thus, we aimed to evaluate the genotoxic effects of semi-synthetic isodillapiole on the nuclei of neuroblasts (larvae) and oocytes (females) and the mean oviposition rates of the females over four generations (G1, G2, G3, and G4) of Ae. aegypti. METHODS: Larvae were captured in the city of Manaus, Amazonas state, Brazil, and exposed to isodillapiole in bioassays (20, 40, and 60 µg/mL) and a negative control (0.05% DMSO in tap water) for 4 h. The cerebral ganglia were extracted from the larvae and oocytes from the adult females to prepare slides for cytogenetic analysis. Breeding pairs were established and eggs counts were quantified taken after the bioassays. RESULTS: The analysis of 20,000 interphase nuclei of neuroblasts and oocytes indicated significant genotoxicity (micronuclei, budding, polynucleated cells, and other malformations) compared to that of the control. Metaphasic and anaphasic nuclei presented chromosomal breaks; however, no significant variation and damage was observed in the negative control. A significant reduction in mean oviposition rates was also recorded following exposure to isodillapiole over the four generations (G1, G2, G3, and G4). CONCLUSIONS: The toxic and genotoxic effects of isodillapiole on Ae. aegypti were caused by reduced oviposition in the females and nuclear abnormalities over the four generations of the trials. Further studies are required, rather than our in vitro assays, to verify the efficacy of exposure to this compound for controlling Ae. aegypti.


Subject(s)
Animals , Female , Aedes , Insecticides/toxicity , Oviposition , DNA Damage , Brazil , Larva
15.
Mem. Inst. Oswaldo Cruz ; 115: e200019, 2020. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135223

ABSTRACT

BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES In the present study we explored the role of TcNDPK1 in DNA damage responses. METHODS TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA repair enzymes were evaluated. FINDINGS Bacteria decreased about 15-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP)ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite's genome integrity.


Subject(s)
Trypanosoma cruzi/enzymology , DNA Damage , Nucleoside-Diphosphate Kinase/metabolism , Trypanosoma cruzi/genetics , Poly(ADP-ribose) Polymerases , Nucleoside-Diphosphate Kinase/genetics , DNA Repair
16.
São Paulo; s.n; s.n; 2020. 77 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1292751

ABSTRACT

As primeiras células responsáveis pela percepção olfatória são os neurônios olfatórios (OSNs) presentes no epitélio olfatório (EO) da cavidade nasal, que reconhecem moléculas voláteis presentes no ar, denominadas odorantes, através de receptores específicos. Diferentemente de neurônios do sistema nervoso central (SNC), que estão relativamente protegidos de genotoxinas exógenas, OSNs estão em constante contato com agentes potencialmente genotóxicos, incluindo o oxigênio atmosférico. Além disto, em contraste com a maioria dos neurônios do SNC, OSNs são periodicamente repostos através de neurogênese adulta, portanto, possuem um tempo de vida menor do que outros neurônios. A função olfatória diminui durante o envelhecimento normal e patológico, através de mecanismos que ainda não estão totalmente claros. Em doenças neurodegenerativas, a perda do olfato é um dos sintomas iniciais e é utilizada como marcador de resposta a alguns tratamentos. Relações causais entre deficiências em reparo de DNA e neurodegeneração já foram demonstradas em vários modelos experimentais. No entanto, ainda não se sabe se alterações nessas vias contribuem para a perda olfatória observada nessas condições, provavelmente porque não há dados disponíveis na literatura sobre vias de reparo de DNA em OSNs. Por isso, o objetivo deste estudo foi caracterizar as vias de reparo de DNA presentes em populações de OSNs maduros e seus precursores. Analisamos dados de expressão de genes de reparo extraídos de dois transcriptomas diferentes, um relacionado à idade e outro, ao estágio de diferenciação destes neurônios. Em seguida, validamos os resultados obtidos da análise in silico através de PCR em tempo real utilizando amostras de EO de camundongos da linhagem C57BL/6J em duas idades (neonatos e com três semanas de idade). Nossos resultados indicam que OSNs são proficientes em todas as vias de reparo de excisão analisadas, apresentando expressão detectável de genes essenciais de cada via. A comparação entre populações enriquecidas em precursores ou em neurônios maduros, nas duas análises, sugere que a atividade de pelo menos quatro vias de reparo de excisão é menor em camundongos jovens, quando comparados aos neonatos, sugerindo, portanto, que há diminuição na expressão durante a diferenciação destas células. Esta observação vai corrobora com dados da literatura que mostraram que a expressão e atividade de proteínas de reparo em células proliferativas é maior do que em célulasterminalmente diferenciadas. Para testar a hipótese de que, por estarem em constante contato com agentes genotóxicos, OSNs acumulam mais lesões em DNA do que células no SNC, comparamos os níveis de lesões em DNA obtido de amostras de EO e de bulbo olfatório (BO), e de córtex temporal (CT), uma região cerebral que não apresenta taxas significativas de neurogênese e não expostas ao ambiente externo. A taxa de lesão foi calculada a partir de dados obtidos por PCR de longa extensão. Resultados obtidos utilizando EO, BO e CT de camundongos com três semanas de idade mostram que a amplificação em amostras de CT é muito menor do que em EO ou BO, sugerindo que neurônios do SNC acumulam mais lesões do que neurônios de regiões que apresentam neurogênese, mesmo que estas estejam constantemente expostas a agentes genotóxicos exógenos. Além disso, a eficiência de amplificação de fragmentos longos de DNA mitocondrial (mtDNA) foi menor em EO do que em BO, sugerindo que a constante exposição ao oxigênio atmosférico contribui para o acúmulo de lesões ao mtDNA, que é mais suscetível do que o DNA nuclear. Esse trabalho demonstra, pela primeira vez, que OSNs expressam proteínas essenciais de vias de reparo de DNA, cuja expressão decresce durante o processo de maturação dos neurônios olfatórios. Esses resultados devem contribuir para o entendimento dos mecanismos de manutenção da integridade genômica nestas células tão únicas


The first cells responsible for olfactory perception are the olfactory sensory neurons (OSNs), located in the olfactory epitelhium (OE) in the nasal cavity, which recognize volatile molecules in the air, called odorants, through olfactory receptors. Unlike neurons located in the central nervous system (CNS), which are relatively protected from exogenous toxins, OSNs are in constant contact with genotoxic agents, including atmospheric oxygen. Moreover, in contrast with most neurons in CNS, OSNs are periodically replaced through adult neurogenesis, therefore, having shorter lifespan than most neurons. Olfactory function decreases during normal and pathological aging, through mechanisms that are still not fully understood. In neurodegenerative diseases, olfactory loss is an early symptom and, in some cases, is used as a treatment response marker. DNA repair defects have been causally linked with neurodegeneration in different experimental models. However, it still unclear whether DNA repair alterations contribute to olfactory loss in these conditions, probably because there are no data available on DNA repair dynamic in OSNs. Therefore, our goal was to characterize the DNA repair pathways present in precursor and mature OSNs populations. We analyzed gene expression data from age-related and differentiation stage-related transcriptomes of these neurons, and validated the results by real time PCR using mouse OE samples from C57BL/6J lineage in two different ages (newborns and three weeks old). Our results indicate that OSNs are proficient in all DNA repair pathways investigated, showing detectable expression of essential genes from each pathway. When comparing populations enriched for mature OSNs or its precursors, our results suggest that the activities of at least four repair pathways are lower in young mice than in newborns, suggesting that DNA repair expression decreases during OSNs differentiation. This observation is consistent with published data showing that the expression and activities of repair proteins is lower in terminally differentiated than in proliferative cells . To test the hypothesis that OSNs would accumulate more DNA damage than CNS neurons, since they are in constant contact wtih genotoxic agents, we compared DNA damage levels in nuclear and mitochondrial DNA from OE, olfactory bulb (OB), and temporal cortex (TC) samples. We chose to use the TC region and a non-olfactory related control as it does not show significant adult neurogenesis and it is not exposed to external environment. Lesion rate wascalculated from data obtained by long extension PCR. Results from 3 weeks old mice OE, OB and TC samples showed that the amplification in TC samples is much lower than OE or OB samples, suggesting that neurons in CNS accumulate more damage than neurons that undergo neurogenesis. Besides, lesion frequency was higher in OE mitochondrial DNA (mtDNA) than in OB, suggesting that the constant exposure to atmospheric oxygen may contribute to accumulation of mtDNA lesions. This work demonstrates, for the first time, that OSNs are proficient in at least four DNA repair pathways, and that expression of key genes in these pathways decreases with differentiation. These results will contribute to better our understanding of the mechanisms involved in genomic stability in such unique cell types


Subject(s)
Olfactory Bulb , Smell , DNA Damage , DNA , Nasal Cavity , Computer Simulation , Central Nervous System , Receptors, Odorant , Neurodegenerative Diseases
17.
São Paulo; s.n; s.n; 2020. 133 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1292693

ABSTRACT

A regulação da fosforilação/desfosforilação das proteínas é o eixo central de muitas cascatas de sinalização. A fosfatase DUSP3, constituída apenas por um único domínio catalítico, desempenha papéis fundamentais na proliferação e senescência celular. Nas células HeLa, submetidas ao estresse genotóxico, o DUSP3 interage fisicamente com as proteínas HNRNPC, mas o efeito dessa função molecular ainda é desconhecido. Aqui demostramos que a ausência de DUPS3 mantem a proteína HNRNPC1/C2 num estado hiperfosforilado. Para entender melhor o envolvimento da interação DUSP3-HNRNPC nas funções biológicas da HNRNPC1/C2, foram estudadas células de fibroblasto deficientes de DUSP3. Foi analisado o efeito da deficiência de DUSP3 na biogênese dos ribossomos através do ensaio de perfil de polirribossomos e quantificação dos rRNAs com RT-qPCR. Os resultados mostraram que a deficiência de DUSP3 não afeta a maturação das subunidades ribossômicas, mas teria um impacto na transcrição dos pré-rRNAs e no acumulo das espécies 47S/45S. A expressado de genes contendo sequencias IRES foi analisado através do RT-qPCR e sua tradução ao longo do ciclo e em condições de estresse. Da expressão, não existe nenhuma diferença nos níveis de transcrição dos genes c-myc e xiap nas células normais e deficientes de DUSP3 em condições basais. Embora a síntese destas proteínas é maior nas células deficientes, mantendo um nível maior de tradução ao longo de todo o ciclo. Sob condições de estresse, esta duas proteínas sempre mantem uma maior expressão nas células Knockdown para DUSP3. Neste trabalho também foi estabelecido a presença de DUSP3 nos complexos da subunidade 40S, através do analise das frações obtidas do ensaio de polirribossomos e interação in vitro (Co-IP). A presença de DUSP3 nas subunidades 40S, os monossomas 80S e polissomos poderia ser através da interação direta com proteínas que possuem um domínio RRM e seria dependente dos complexos formados pelas proteínas e seus RNAs alvos. Aqui mostramos a interação in vitro de DUSP3 com a proteína PABP (com quatro domínios RRM), proteína que tem um papel importante na manutenção da taxa global de tradução, esta interação é enfraquecida na ausência de RNAs. A deficiência de DUSP3 também teria um impacto na interação das proteínas HNRNPC1/C2 e P53 in vitro. A ausência de DUSP3 diminui a interação HNRNPC-P53 através da hiperfosforilação da proteina HNRNPC1/C2. A perda desta interação, aumentaria os níveis da proteína P53 na célula deficiente de DUSP3 e poderia gerar parada no ciclo celular. Através de ensaios de imunofluorescência, se observo uma maior taxa de transcrição global na célula deficiente de DUSP3. Por fim, aqui demostramos que a interação direta de DUSP3 e HNRNPC1/C2 vai permitir a regulação das funções biológicas desta proteína, e a ausência de DUSP3 vai ter efeitos pleiotrópicos na homeostase da célula


inglêsProtein phosphorylation/dephosphorylation regulation is a central axis of many signaling cascades. DUSP3 phosphatase, consisting only of a single catalytic domain, plays key roles in cell proliferation and senescence. In HeLa cells subjected to genotoxic stress, DUSP3 physically interacts with HNRNPC proteins, but the effect of this molecular function is still unknown. Here we demonstrate that the absence of DUPS3 keeps the HNRNPC1/C2 proteins in a hyperphosphorylated state. To better understand the involvement of DUSP3- HNRNPC interaction on the biological functions of HNRNPC1/C2, DUSP3 deficient fibroblast cells were studied. The effect of DUSP3 deficiency on ribosome biogenesis was analyzed by polyribosome profile assay and RT-qPCR for rRNA quantification. The results showed that DUSP3 deficiency does not affect ribosomal subunit maturation, but would have an impact on transcription of pre-rRNAs and accumulation of 47S / 45S species. The expression of genes containing IRES sequences was analyzed by RT-qPCR and their translation throughout the cycle and under stress conditions. From expression, there is no difference in transcriptional levels of c-myc and xiap genes in normal and DUSP3 deficient cells under basal conditions. Although, the synthesis of these proteins is higher in deficient cells and these maintain a higher level of translation throughout the cell cycle. Under stress conditions, these two proteins always maintain higher expression in Knockdown cells for DUSP3. In this work, the presence of DUSP3 in the 40S ribosomal subunit complexes was also established by analyzing the fractions obtained from the polyribosome assay and in vitro interaction (CoIP). The presence of DUSP3 in the 40S subunits, 80S monosomes and polysomes could be through direct interaction with proteins that have an RRM domain and would be dependent on the complexes formed by the proteins and their target RNAs. Here we show the in vitro interaction of DUSP3 with PABP protein (with four RRM domains), a protein that plays an important role in maintaining the overall translation rate, this interaction is weakened in the absence of RNAs. DUSP3 deficiency would also have an impact on the interaction of HNRNPC1/C2 and P53 proteins in vitro. The absence of DUSP3 decreases HNRNPC-P53 interaction through hyperphosphorylation of the HNRNPC1/C2 proteins. Loss of this interaction would increase P53 protein levels in the DUSP3 deficient cell and could lead to cell cycle arrest. Through immunofluorescence assays, a higher overall transcription rate is observed in the DUSP3 deficient cell. Finally, we demonstrate that the direct interaction of DUSP3 and HNRNPC1/C2 will allow the regulation of the biological functions of this protein, and the absence of DUSP3 will have pleiotropic effects on cell homeostasis


Subject(s)
DNA Damage , Cell Cycle , Cells , Genes, myc , Origin of Life , Maintenance , Phosphorylation , Polyribosomes , Cell Cycle Checkpoints , Fibroblasts , Homeostasis
18.
Braz. j. med. biol. res ; 53(5): e9331, 2020. graf
Article in English | LILACS | ID: biblio-1098113

ABSTRACT

The melamine and cyanuric acid (CA) complex has been suggested to cause the toxic effects observed in melamine-contaminated food or milk. However, the cytotoxic and genotoxic effects of co-exposure to melamine and CA are not fully clear. Therefore, the cytotoxic effects of melamine and CA were first examined by co‐exposure in human kidney 293 cells using the MTT assay. During a 24-h period for the three concentrations tested (0.5, 1, and 5 mg/mL), neither melamine nor CA alone showed significant toxic effects on 293 cells at 0.5 mg/mL, while higher concentrations led to decreased in cell viability. However, co-exposure to several combinations of melamine and CA [100:1, 10:1, 1:10, and 1:100 (v:v), at a final concentration of 0.5 mg/mL] did cause cytotoxicity with higher levels of CA leading to higher cytotoxicity. By contrast, while neither melamine nor CA alone induced phosphorylated-H2AX (γH2AX) foci formation, melamine and CA at a 100:1 ratio induced γH2AX foci 24 h post-treatment. The alkaline comet assay also revealed the presence of DNA damage following melamine and CA co-exposure. In vivo assay also revealed the presence of melamine-CA complex in the kidney. These data indicated that the cytotoxic and genotoxic effects of melamine and CA co-exposure differ from those of melamine or CA alone.


Subject(s)
Humans , Animals , Rats , Triazines/toxicity , DNA Damage/drug effects , Cell Survival/drug effects , Kidney/drug effects , Time Factors , Kidney/embryology , Mutagenicity Tests
19.
Clin. biomed. res ; 40(1): 21-26, 2020.
Article in Portuguese | LILACS | ID: biblio-1116646

ABSTRACT

Introdução: Evidências têm mostrado uma associação entre anemia e Diabetes Mellitus. Contudo, a relação entre anemia e Diabetes Mellitus Gestacional (DMG) ainda não está bem estabelecida, bem como sua repercussão na instabilidade genômica. Portanto, objetivou-se verificar a associação entre anemia e instabilidade genômica em mulheres com DMG atendidas em um hospital universitário. Métodos: Estudo transversal com mulheres apresentando diagnóstico de DMG que realizaram pré-natal no Hospital Universitário de Santa Maria (RS). Informações referentes ao DMG, anemia e suplementação de ferro foram obtidas nos prontuários. A instabilidade genômica foi avaliada pelo ensaio de citoma em micronúcleos em células bucais (BMCyt). Resultados: Das 44 gestantes avaliadas, 28,6% apresentaram anemia e 79,5% foram suplementadas com ferro. Das gestantes que realizaram suplementação, 75,0% não apresentaram anemia gestacional. Níveis de hemoglobina não se associaram com a instabilidade genomica (p > 0,05), mas foi observada uma associação entre brotos nucleares e os níveis de glicemia (r = 0,977; p = 0,003). Conclusão: Não foi verificado associação entre anemia e instabilidade genômica em mulheres com DMG.(AU)


Introduction: There is evidence of an association between anemia and diabetes mellitus. However, the relationship between anemia and gestational diabetes mellitus (GDM) remains to be established, as well as its impact on genomic instability. Therefore, we aimed to examine the association between anemia and genomic instability in women with GDM treated at a university hospital. Methods: A cross-sectional study of women with a diagnosis of GDM who received prenatal care at the University Hospital of Santa Maria, southern Brazil. Data on GDM, anemia, and iron supplementation were obtained from medical records. Genomic instability was assessed by the buccal micronucleus cytome (BMCyt) assay. Results: Of 44 pregnant women evaluated, 28.6% had anemia and 79.5% received iron supplementation; of the latter, 75.0% did not have gestational anemia. Hemoglobin levels were not associated with genomic instability (p > 0.05), but an association was found between nuclear buds and blood glucose levels (r = 0.977; p = 0.003). Conclusion: There was no association between anemia and genomic instability in women with GDM.(AU)


Subject(s)
Humans , Female , Pregnancy , Adult , Young Adult , Diabetes, Gestational/genetics , Genomic Instability , Anemia/genetics , Prenatal Care , Blood Glucose/analysis , DNA Damage , Hemoglobins/analysis , Cross-Sectional Studies , Anemia, Iron-Deficiency/complications , Anemia, Iron-Deficiency/diet therapy , Anemia, Iron-Deficiency/genetics , Iron, Dietary/therapeutic use , Anemia/complications , Anemia/diet therapy
20.
J. oral res. (Impresa) ; 8(6): 505-509, dic. 28, 2019. ilus, graf, tab
Article in English | LILACS | ID: biblio-1224479

ABSTRACT

Objectives: A systematic review was conducted to evaluate effectiveness and safety of beta carotenes for the treatment of oral leukoplakia regarding clinical resolution and prevention of malignant transformation. Material and Methods: The systematic search was conducted in three electronic databases and the study's selection was performed according to pre-set eligibility criteria. Four studies evaluating the efficacy of beta carotenes in oral leukoplakia compared to placebo were included in the review; three of which were assigned for quantitative analysis. Data were extracted, tabulated, quality assessed and statistically analyzed. Results: The meta-analysis revealed that when comparing clinical resolution the beta carotene group favored was favored compared to placebo, with statistically significant difference. However, a meta-analysis comparing beta carotene and placebo groups regarding malignant transformation as a primary outcome failed to show any significant benefit. Furthermore, results showed evidence of beta carotene safety. Conclusion: the overall quality of evidence about efficacy of beta carotene in oral leukoplakia treatment was not high. However, given the obvious safety of this agent, data suggests it could have a promising effect in clinical improvement of oral leukoplakia lesions. However, no evidence supporting its benefits in reducing risk of malignant transformation in these lesions was found. Therefore, further long term, well designed randomized clinical trials are highly recommended.


Introducción: el cáncer oral es un problema grave con alta mortalidad y morbilidad, a pesar de la disponibilidad de los mejores tratamientos. Uno de los factores más importantes para una mortalidad tan alta es su diagnóstico tardío. La mejor manera de enfrentar un problema de este tipo es evitar su aparición creando conciencia entre la población y tenendo un diagnóstico más temprano. El cáncer oral es una enfermedad multifactorial, donde el daño genómico tiene un papel. Se ha demostrado que los micronúcleos (MNi) son un biomarcador importante y en este estudio se utilizó como una herramienta para crear conciencia sobre el riesgo de cáncer oral. Objetivo: evaluar y comparar la frecuencia de MNi en fumadores sin ninguna lesión oral visible (Grupo I) y no fumadores sanos (Grupo II). Materiales y métodos: se obtuvieron citoestimuladores de fumadores sauditas (n = 15, Grupo I) sin ninguna lesión oral visible y no fumadores sanos (n = 15, control, Grupo II) y se tiñeron con hemotoxilina y eosina para evaluar la frecuencia de MNi y las observaciones fueron sometidas a análisis estadístico utilizando la prueba t de Student. Resultados: La frecuencia media de MNi en el Grupo I fue significativamente mayor (p<0.05) que en el Grupo II. El estudio ayuda a educar, motivar y crear conciencia, alentando así a los pacientes a dejar de fumar, y evitando así el cáncer oral antes de su inicio.


Subject(s)
Humans , Mouth Neoplasms/genetics , Micronucleus Tests , Mouth Mucosa/pathology , Saudi Arabia , DNA Damage , Leukoplakia, Oral , Biomarkers , Delayed Diagnosis , Smokers , Non-Smokers
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