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1.
Inflammopharmacology ; 32(5): 3327-3345, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39133352

RESUMO

Wounds or chronic injuries are associated with high medical costs so, develop healing-oriented drugs is a challenge for modern medicine. The identification of new therapeutic alternatives focuses on the use of natural products. Therefore, the main goal of this study was to evaluate the healing potential and anti-inflammatory mechanism of action of extracts and the main compounds derived from Myrciaria plinioides D. Legrand leaves. The antimicrobial activity of leaf extracts was analyzed. Cell viability, cytotoxicity and genotoxicity of plant extracts and compounds were also assessed. Release of pro- and anti-inflammatory cytokines and TGF-ß by ELISA, and protein expression was determined by Western Blot. The cell migration and cell proliferation of ethanol and aqueous leaf extracts and p-coumaric acid, quercetin and caffeic acid compounds were also evaluated. The aqueous extract exhibited antibacterial activity and, after determining the safety concentrations in three assays, we showed that this extract induced p38-α MAPK phosphorylation and the same extract and the p-coumaric acid decreased COX-2 and caspase-3, -8 expression, as well as reduced the TNF-α release and stimulated the IL-10 in RAW 264.7 cells. In L929 cells, the extract and p-coumaric acid induced TGF-ß release, besides increasing the process of cell migration and proliferation. These results suggested that the healing properties of Myrciaria plinioides aqueous extract can be associated to the presence of phenolic compounds, especially p-coumaric acid, and/or glycosylated metabolites.


Assuntos
Anti-Inflamatórios , Movimento Celular , Extratos Vegetais , Folhas de Planta , Cicatrização , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Cicatrização/efeitos dos fármacos , Camundongos , Células RAW 264.7 , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular , Citocinas/metabolismo , Myrtaceae/química , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação
2.
Mol Biol Rep ; 50(8): 7105-7111, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37326748

RESUMO

BACKGROUND: A novel virulent bacteriophage infecting phytobacteria Pseudomonas cichorii (P. cichorii) was isolated from leafy vegetables in Brazil. P. cichorii is a Gram-negative soil phytobacterium, the causal agent of a number of economically important plant diseases worldwide. METHODS AND RESULTS: In this study, a new phage specific for P. cichorii was isolated from solid samples (lettuce, chicory and cabbage), designated vB_Pci_PCMW57. Electron microscopy revealed a small virion (~ 50-nm-diameter icosahedral capsid) with a short, non-contractile tail. The genome of vB_Pci_PCMW57 is 40,117 bp in size, with a GC content of 57.6% and encodes 49 open reading frames. The phage is genetically similar to P. syringae phages Pst_GM1 and Pst_GIL1, and the P. fluorescens phages WRT and KNP. According to electron microscopy and whole-genome sequence analysis, vB_Pci_PCMW57 should be classified as a Caudoviticetes, family Autographiviridae, subfamily Studiervirinae. CONCLUSIONS: The complete phage genome was annotated, and the sequence identity of the virus with other Pseudomonas viruses was higher than 95%. To our knowledge, this is the first report of a bacteriophage infecting Pseudomonas cichorii.


Assuntos
Bacteriófagos , Bacteriófagos/genética , Genoma Viral , Análise de Sequência de DNA , Pseudomonas/genética , Fases de Leitura Aberta/genética , Filogenia
3.
Environ Geochem Health ; 45(10): 7081-7097, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37542205

RESUMO

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC-MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations.


Assuntos
Dano ao DNA , Hidrocarbonetos Policíclicos Aromáticos , Masculino , Humanos , Feminino , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Poeira/análise , Antracenos/análise , Carvão Mineral/toxicidade , Carvão Mineral/análise , Estresse Oxidativo
4.
Ecotoxicol Environ Saf ; 212: 111935, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33578128

RESUMO

During the welding activities many compounds are released, several of these cause oxidative stress and inflammation and some are considered carcinogenic, in fact the International Agency for Research on Cancer established that welding fumes are carcinogenic to humans. The aim of the present study was to analyze the cytotoxic and genotoxic potential of exposure to welding fumes and to determine concentrations of metals in blood and urine of occupationally exposed workers. We included 98 welders and 100 non-exposed individuals. Our results show significant increase in the frequency of micronuclei (MN), nucleoplasmic bridges (NPB), nuclear buds (NBUD) and necrotic cells (NECR) in cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, as well as in the telomere length (TL) of the exposed individuals with respect to the non-exposed group. In the analysis of the concentrations of inorganic elements using PIXE method, were found higher concentrations of Cr, Fe and Cu in the urine, and Cr, Fe, Mg, Al, S, and Mn in the blood in the exposed group compared to the non-exposed group. A significant correlation was observed between MN and age and between NPB and years of exposure. Additionally, we found a significant correlation for TL in relation to MN, NPB, age and years of exposure in the exposed group. Interestingly, a significant correlation between MN and the increase in the concentration of Mg, S, Fe and Cu in blood samples of the exposed group, and between MN and Cr, Fe, Ni and Cu in urine. Thus, our findings may be associated with oxidative and inflammatory damage processes generated by the components contained in welding fumes, suggesting a high occupational risk in welding workers.


Assuntos
Poluentes Ocupacionais do Ar/análise , Bioensaio , Testes para Micronúcleos/métodos , Exposição Ocupacional/análise , Telômero , Biomarcadores/análise , Citocinese , Dano ao DNA , Humanos , Linfócitos , Estresse Oxidativo , Soldagem
5.
Genet Mol Biol ; 43(3): e20190134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609278

RESUMO

Cell cycle alterations are among the principle hallmarks of cancer. Consequently, the study of cell cycle regulators has emerged as an important topic in cancer research, particularly in relation to environmental exposure. Particulate matter and coal dust around coal mines have the potential to induce cell cycle alterations. Therefore, in the present study, we performed chemical analyses to identify the main compounds present in two mineral coal samples from Colombian mines and performed systems chemo-biology analysis to elucidate the interactions between these chemical compounds and proteins associated with the cell cycle. Our results highlight the role of oxidative stress generated by the exposure to the residues of coal extraction, such as major inorganic oxides (MIOs), inorganic elements (IEs) and polycyclic aromatic hydrocarbons (PAH) on DNA damage and alterations in the progression of the cell cycle (blockage and/or delay), as well as structural dysfunction in several proteins. In particular, IEs such as Cr, Ni, and S and PAHs such as benzo[a]pyrene may have influential roles in the regulation of the cell cycle through DNA damage and oxidative stress. In this process, cyclins, cyclin-dependent kinases, zinc finger proteins such as TP53, and protein kinases may play a central role.

6.
Ecotoxicol Environ Saf ; 171: 264-273, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30612014

RESUMO

Diesel engine exhaust (DEE), which is the product of diesel combustion, is considered carcinogenic in humans. It comprises toxic gases, polycyclic aromatic hydrocarbons (PAHs) and particulate matter which can reach the pulmonary parenchyma and trigger various diseases, including cancer. The aim of the present study was to evaluate the potential cytotoxic and genotoxic effects of DEE exposure on peripheral blood and buccal epithelial cells in mechanics occupationally exposed to DEE. We recruited 120 exposed mechanics and 100 non-exposed control individuals. Significant differences were observed between the two groups in terms of percentage of tail DNA and damage index (DI) in the alkaline comet assay; levels of biomarkers by cytokinesis-block micronucleus cytome (CBMN-Cyt) assay; frequency of micronucleus (MN), nucleoplasmic bridge (NPB), nuclear bud (NBUD) and apoptotic cells (APOP) and levels of biomarkers for micronucleus, karyorrhexis (KRX), karyolysis (KRL) and condensed chromatin (CC) by the buccal micronucleus cytome (BM-Cyt) assay. A significant and positive correlation was found between the frequency of MN in lymphocytes and buccal cells in the exposed group. Also, there was a significant correlation between age and percentage of tail DNA and DI in the comet assay, APOP and MN in the CBMN-Cyt assay and NBUD and MN in the BM-Cyt assay. Additionally, we found a positive and significant correlation of MN frequency in lymphocytes and buccal cells and age and MN frequency in lymphocytes with the time of service (years). Regarding lifestyle-related factors, a significant correlation was observed between meat and vitamin consumption and NBUD formation on CBMN-Cyt and between meat consumption and MN formation on CBMN-Cyt. Of the BM-Cyt biomarkers, there was a correlation between alcohol consumption and NBUD formation and between binucleated cell (BN), pyknosis (PYC), CC and KRL occurrence and family cancer history. These results are the first data in Colombia on the cytotoxic and genotoxic effects induced by continuous exposure to DEE and thus showed the usefulness of biomarkers of the comet, CBMN-Cyt and BM-Cyt assays for human biomonitoring and evaluation of cancer risk in the exposed populations.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Apoptose/efeitos dos fármacos , Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Emissões de Veículos/toxicidade , Células Cultivadas , Colômbia , Ensaio Cometa , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos/métodos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Exposição Ocupacional/análise
7.
Arch Toxicol ; 90(9): 2063-2076, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27342245

RESUMO

Anthracyclines, e.g., doxorubicin (DOX), and anthracenediones, e.g., mitoxantrone (MTX), are drugs used in the chemotherapy of several cancer types, including solid and non-solid malignancies such as breast cancer, leukemia, lymphomas, and sarcomas. Although they are effective in tumor therapy, treatment with these two drugs may lead to side effects such as arrhythmia and heart failure. At the same clinically equivalent dose, MTX causes slightly reduced cardiotoxicity compared with DOX. These drugs interact with iron to generate reactive oxygen species (ROS), target topoisomerase 2 (Top2), and impair mitochondria. These are some of the mechanisms through which these drugs induce late cardiomyopathy. In this review, we compare the cardiotoxicities of these two chemotherapeutic drugs, DOX and MTX. As described here, even though they share similarities in their modes of toxicant action, DOX and MTX seem to differ in a key aspect. DOX is a more redox-interfering drug, while MTX induces energy imbalance. In addition, DOX toxicity can be explained by underlying mechanisms that include targeting of Top2 beta, mitochondrial impairment, and increases in ROS generation. These modes of action have not yet been demonstrated for MTX, and this knowledge gap needs to be filled.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Cardiopatias/induzido quimicamente , Mitoxantrona/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antígenos de Neoplasias/metabolismo , Cardiotoxicidade , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Humanos , Ferro/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Ligação a Poli-ADP-Ribose , Espécies Reativas de Oxigênio/metabolismo , Inibidores da Topoisomerase II/farmacologia
8.
J Toxicol Environ Health A ; 79(18): 825-36, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27587288

RESUMO

Grapes are one of the most commonly consumed fruit, in both fresh and processed forms; however, a significant amount is disposed of in the environment. Searching for a use of this waste, the antigenotoxic, antimutagenic, and antioxidant activities of aqueous extracts from organic and conventional Vitis labrusca leaves were determined using V79 cells as model. The antigenotoxic activity was analyzed by the alkaline comet assay using endonuclease III and formamidopyrimidine DNA glycosylase enzymes. The antimutagenic property was assessed through the micronucleus (MN) formation, and antioxidant activities were assessed using 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA) assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH(●)) radical scavenging, as well as with superoxide dismutase (SOD) and catalase (CAT) activity assays. In addition, phenolic content and ascorbic acid levels of both extracts were determined. Data showed that both organic and conventional grapevine leaves extracts possessed antigenotoxic and antimutagenic properties. The extract of organic leaves significantly reduced intracellular reactive oxygen species (ROS) levels in V79 cells, and displayed greater ability for DPPH(●) scavenging and higher SOD and CAT activities than extract from conventional leaves. Further, the extract from organic leaves contained higher phenolic and ascorbic acid concentrations. In summary, extracts from organic and conventional grape leaves induced important in vitro biological effects.


Assuntos
Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Ácido Ascórbico/análise , Agricultura Orgânica , Polifenóis/análise , Vitis/química , Animais , Linhagem Celular , Cricetulus , Testes para Micronúcleos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química
9.
Int J Food Sci Nutr ; 67(4): 479-88, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27018203

RESUMO

Dietary total antioxidant capacity (DTAC) seems to be associated with reducing risk of diseases. However, data about the influence of the DTAC on oxidative stress parameters are scarce. The aim of this study was to estimate the DTAC and its influence on plasma total antioxidant capacity (PTAC), and damage to lipids, proteins and DNA in healthy women. It was found a positive correlation between DTAC and PTAC in young and healthy subjects, where presumably the endogenous defenses are fully functional. DTAC and PTAC were positively correlated with the intake of known antioxidants, including vitamin C and polyphenols. The DTAC exhibited a negative correlation with lipid oxidative damage, while PTAC showed a negative correlation with DNA damage. This data contributes to better understanding of the recommended dietary antioxidant intake for promoting health.


Assuntos
Antioxidantes/administração & dosagem , Dano ao DNA , Dieta Saudável , Peroxidação de Lipídeos , Estresse Oxidativo , Carbonilação Proteica , Adolescente , Adulto , Antioxidantes/análise , Ácido Ascórbico/administração & dosagem , Biomarcadores/sangue , Brasil , Exercício Físico , Feminino , Estilo de Vida Saudável , Humanos , Hidrocortisona/sangue , Polifenóis/administração & dosagem , Autorrelato , Estresse Psicológico/sangue , Estresse Psicológico/fisiopatologia , Adulto Jovem
10.
J Toxicol Environ Health A ; 78(18): 1170-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26383782

RESUMO

Arrabidaea chica Verlot (Bignoniaceae) has been used as a medicinal herb to treat anemia, hemorrhage, inflammation, intestinal colic, hepatitis, and skin infections in the Brazilian Amazon region. Studies have demonstrated the healing properties of extracts obtained from A. chica leaves, which contain anthocyanins and flavonoids. However, few investigations have assessed the safe use of this plant species. In this study, mutagenic and genotoxic effects of a crude aqueous extract, a butanolic fraction, and aqueous waste from A. chica leaves were evaluated using the Salmonella/microsome assay in TA98, TA97a, TA100, TA102, and TA1535 strains and the alkaline comet assay in Chinese hamster ovary (CHO) cell culture with and without metabolic activation. The crude aqueous extract, butanolic fraction, and aqueous waste were not mutagenic in any of the Salmonella typhimurium strains tested, and showed negative responses for genotoxicity in CHO cells. High-performance liquid chromatography (HPLC) analysis indicated the presence of phenolic acids and flavonoids such as rutin and luteolin. The lack of mutagenic/genotoxic effects might be due to phytochemical composition with high concentrations of known anti-inflammatory compounds. Thus, the crude aqueous extract, butanolic fraction, and aqueous waste from A. chica leaves do not appear to pose short-term genotoxic risks.


Assuntos
Bignoniaceae/química , Extratos Vegetais/farmacologia , Animais , Células CHO , Cromatografia Líquida de Alta Pressão , Ensaio Cometa , Cricetulus , Dano ao DNA , Microssomos/efeitos dos fármacos , Mutagênicos/farmacologia , Extratos Vegetais/efeitos adversos , Folhas de Planta/química , Plantas Medicinais/efeitos adversos , Plantas Medicinais/química , Salmonella typhimurium/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-24561378

RESUMO

The organoselenium compound, dicholesteroyl diselenide (DCDS) is a structural analogue of diphenyl diselenide (DPDS) and may be considered as a promising antioxidant drug in vivo. Nevertheless, little is known about the toxicological properties of DCDS. In the present study we evaluated the cytotoxic, genotoxic and mutagenic properties of DCDS in Chinese hamster lung fibroblasts (V79) and in strains of the yeast Saccharomyces cerevisiae, proficient and deficient in several DNA-repair pathways. The results with V79 cells show that DCDS induced cytotoxicity, GSH depletion and elevation of lipid peroxidation at lower concentrations than did DPDS. DCDS also generated single- and double-strand DNA breaks in V79 cells, both in the presence and in the absence of metabolic activation, as revealed by alkaline and neutral comet assays. Moreover, the induction of oxidative DNA base-damage was demonstrated by means of a modified comet assay with formamidopyrimidine-DNA glycosylase and endonuclease III. Treatment with DCDS also induced micronucleus formation in V79 cells as well as point and frame-shift mutations in a haploid wild-type strain of S. cerevisiae. Yeast mutants defective in base excision-repair proteins were the most sensitive to DCDS. Pre-incubation with N-acetylcysteine reduced DCDS's oxidative, genotoxic and mutagenic effects in yeast and in V79 cells. Our findings indicate that the presence of cholesteroyl substituents in DCDS results in elevation of its cytotoxic and genotoxic potential compared with that of DPDS in yeast and in V79 cells. However, due to dose-dependent contrasting behaviour of organoselenium compounds and differences in their toxicity in in vitro and in vivo systems, further studies are needed in order to establish the non-toxic concentration range for treatment in mammals.


Assuntos
Colesterol/análogos & derivados , Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Mutagênicos/toxicidade , Compostos Organosselênicos/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Animais , Biomarcadores/análise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/toxicidade , Ensaio Cometa , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Mutação da Fase de Leitura/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes para Micronúcleos , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Testes de Toxicidade/métodos
12.
Artigo em Inglês | MEDLINE | ID: mdl-24495929

RESUMO

Stainless steel bands, with or without silver soldered joints, are routinely used in orthodontics. However, little is known about the toxic biological effects of these appliances. The aims of this study were to evaluate the cytotoxic, cytostatic, genotoxic and DNA damage-inducing effects of non-soldered bands (NSB) and silver soldered bands (SSB) on the HepG2 and HOK cell lines and to quantify the amount of ions released by the bands. The 24-h metallic eluates of NSBs and SSBs were quantified by atomic absorption spectrophotometry. An MTT reduction assay was performed to evaluate the cytotoxicity, alkaline and modified comet assays were employed to measure genotoxicity and oxidative DNA damage effects, and cytokinesis-block micronucleus cytome (CBMN-Cyt) assays were used to verify DNA damage, cytostasis and cytotoxicity. Ag, Cd, Cr, Cu and Zn were detected in SSB medium samples, and Fe and Ni were detected in both the SSB and NSB medium samples. The SSB group induced stronger cytotoxic effects than the NSB group in both evaluated cell lines. NSB and SSB induced genotoxicity as evaluated by comet assays; stronger effects were observed in the SSB group. Both groups induced similar increases in the number of oxidative DNA lesions, as detected by the FPG and Endo III enzymes. Nucleoplasmic bridges, biomarkers of DNA misrepair and/or telomere end fusions, were significantly elevated in the SSB group. The SSB eluates showed higher amounts of Ni and Fe than NSB, and all the quantified ions were detected in SSB eluates, including Cd. The SSB eluates were more cytotoxic and genotoxic than the NSB samples. Based on these results, we propose that other brands, materials and techniques should be further investigated for the future manufacture of orthodontic appliances.


Assuntos
Dano ao DNA , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Aparelhos Ortodônticos , Prata/toxicidade , Aço Inoxidável/toxicidade , Cátions , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Meios de Cultura , Células Hep G2 , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Testes para Micronúcleos , Testes de Toxicidade/métodos
13.
Ecotoxicol Environ Saf ; 107: 133-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24927390

RESUMO

During coal mining activities, large quantities of coal dust, ashes, polycyclic aromatic hydrocarbons and metals are released into the environment. This complex mixture presents one of the most important occupational hazards for health of workers. The aim of the present study was to evaluate the genetic damage together with the presence of inorganic elements, in an exposed workers population to coal mining residues of Guajira-Colombia. Thus, 100 exposed workers and 100 non-exposed control individuals were included in this study. To determine genetic damage we assessed the micronucleus (MN) frequencies and nuclear buds in buccal mucosa samples (BMCyt) assay, which were significantly higher in the exposed group than non-exposed control group. In addition, karyorrhectic and karyolytic cells were also significantly higher in the exposed group (cell death). No significant difference was observed between the exposed groups engaged in different mining activities. No correlation between age, alcohol consumption, time of service and MN assay data were found in this study. However, the content of inorganic elements in blood samples analyzed by a Particle-induced X-ray emission technique (PIXE) showed higher values of silicon (Si) and aluminum (Al) in the exposed group. In this study we discuss the possibility of DNA damage observed in the mine workers cells be a consequence of oxidative damage.


Assuntos
Minas de Carvão , Dano ao DNA , Mucosa Bucal/citologia , Exposição Ocupacional/análise , Adulto , Análise Química do Sangue , Estudos de Casos e Controles , Morte Celular , Carvão Mineral/efeitos adversos , Poeira , Humanos , Masculino , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Espectrometria por Raios X , Adulto Jovem
14.
Toxicology ; 508: 153902, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39094917

RESUMO

Glyphosate, the world's most widely used herbicide, has a low toxicity rating despite substantial evidence of adverse health effects. Furthermore, glyphosate-based formulations (GBFs) contain several other chemicals, some of which are known to be harmful. Additionally, chronic, and acute exposure to GBFs among rural workers may lead to health impairments, such as neurodegenerative diseases and cancer. P53 is known as a tumor suppressor protein, acting as a key regulator of the cellular response to stress and DNA damage. Therefore, mutations in the TP53 gene, which encodes p53, are common genetic alterations found in various types of cancer. Therefore, this study aimed to evaluate the cytotoxicity and genotoxicity of GBF in two glioblastoma cell lines: U87MG (TP53-proficient) and U251MG (TP53-mutant). Additionally, the study aimed to identify the main proteins involved in the response to GBF exposure using Systems Biology in a network containing p53 and another network without p53. The MTT assay was used to study the toxicity of GBF in the cell lines, the clonogenic assay was used to investigate cell survival, and the Comet Assay was used for genotoxicity evaluation. For data analysis, bioinformatics tools such as String 12.0 and Stitch 5.0 were applied, serving as a basis for designing binary networks in the Cytoscape 3.10.1 program. From the in vitro test analyses, it was observed a decrease in cell viability at doses starting from 10 ppm. Comet Assay at concentrations of 10 ppm and 30 ppm for the U251MG and U87MG cell lines, respectively observed DNA damage. The network generated with systems biology showed that the presence of p53 is important for the regulation of biological processes involved in genetic stability and neurotoxicity, processes that did not appear in the TP53-mutant network.


Assuntos
Sobrevivência Celular , Dano ao DNA , Glioblastoma , Glicina , Glifosato , Herbicidas , Proteína Supressora de Tumor p53 , Humanos , Glicina/análogos & derivados , Glicina/toxicidade , Herbicidas/toxicidade , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Mutação , Relação Dose-Resposta a Droga
15.
Artigo em Inglês | MEDLINE | ID: mdl-39364577

RESUMO

Valproic acid (VA) is a widely used drug for the treatment of diseases affecting the central nervous system. Due to its epigenetic modulatory potential, it has been studied for possible therapeutic application in anticancer therapies. However, the VA exhibits different side effects in its application. Thus, synthetic coordination complexes with valproate can generate promising candidates for new active drugs with reduced toxicity. In this sense, we investigated the genotoxic and mutagenic potential of the sodium valproate and of the mixed ternary mononuclear Mg complex based on VA with 1,10-phenanthroline (Phen) ligand - [Mg (Valp)2Phen], in Saccharomyces cerevisiae and V79 cells. The MTT and clonal survival assays in V79 cells indicated that the Mg complex has higher cytotoxicity than sodium valproate. A similar cytotoxicity profile is observed in yeast. This fact is possibly due to the intercalation capacity of [Mg(Valp)2Phen], inducing DNA strand breaks, as observed in the comet assay and micronucleus test. In this sense, members of the NER, HR, NHEJ and TLS repair pathways are required for the repair of DNA lesions induced by [Mg(Valp)2Phen]. Interestingly, BER proteins apparently increase the cytotoxic potential of the drug. Furthermore, the [Mg(Valp)2Phen] showed higher cytotoxicity in V79 cells and yeast when compared to sodium valproate indicating applicability as a cytotoxic agent.

16.
Fungal Genet Biol ; 60: 122-32, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24076078

RESUMO

Pso2 protein, a member of the highly conserved metallo-ß-lactamase (MBL) super family of nucleases, plays a central role in interstrand crosslink repair (ICL) in yeast. Pso2 protein is the founder member of a distinct group within the MBL superfamily, called ß-CASP family. Three mammalian orthologs of this protein that act on DNA were identified: SNM1A, SNM1B/Apollo and SNM1C/Artemis. Yeast Pso2 and all three mammalian orthologs proteins have been shown to possess nuclease activity. Besides Pso2, ICL repair involves proteins of several DNA repair pathways. Over the last years, new homologs for human proteins have been identified in yeast. In this review, we will focus on studies clarifying the function of Pso2 protein during ICL repair in yeast, emphasizing the contribution of Brazilian research groups in this topic. New sub-pathways in the mechanisms of ICL repair, such as recently identified conserved Fanconi Anemia pathway in yeast as well as a contribution of non-homologous end joining are discussed.


Assuntos
Reparo do DNA , Endodesoxirribonucleases/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , DNA Fúngico/genética , DNA Fúngico/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Anemia de Fanconi/metabolismo , Instabilidade Genômica
17.
BMC Med Genet ; 14: 93, 2013 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-24053728

RESUMO

BACKGROUND: We investigated a potential link between genetic polymorphisms in genes XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr) with the level of DNA damage and repair, accessed by comet and micronucleus test, in 51 COPD patients and 51 controls. METHODS: Peripheral blood was used to perform the alkaline and neutral comet assay; and genetic polymorphisms by PCR/RFLP. To assess the susceptibility to exogenous DNA damage, the cells were treated with methyl methanesulphonate for 1-h or 3-h. After 3-h treatment the % residual damage was calculated assuming the value of 1-h treatment as 100%. The cytogenetic damage was evaluated by buccal micronucleus cytome assay (BMCyt). RESULTS: COPD patients with the risk allele XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) showed higher DNA damage by comet assay. The residual damage was higher for COPD with risk allele in the four genes. In COPD patients was showed negative correlation between BMCyt (binucleated, nuclear bud, condensed chromatin and karyorrhexic cells) with pulmonary function and some variant genotypes. CONCLUSION: Our results suggest a possible association between variant genotypes in XRCC1 (Arg399Gln), OGG1 (Ser326Cys), XRCC3 (Thr241Met), and XRCC4 (Ile401Thr), DNA damage and progression of COPD.


Assuntos
Dano ao DNA , DNA Glicosilases/genética , Proteínas de Ligação a DNA/genética , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Alelos , Ensaio Cometa , Reparo do DNA , Genótipo , Humanos , Masculino , Metanossulfonato de Metila/química , Pessoa de Meia-Idade , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/patologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
18.
Cell Mol Neurobiol ; 33(8): 1123-33, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23989908

RESUMO

Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage.


Assuntos
Bebidas , Dieta Hiperlipídica , Comportamento Alimentar , Alimentos Orgânicos , Vitis/química , Animais , Antioxidantes/metabolismo , Peso Corporal , Encéfalo/enzimologia , Encéfalo/patologia , Comportamento de Ingestão de Líquido , Masculino , Óxido Nítrico/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
19.
Nutr Cancer ; 65(7): 943-53, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23919376

RESUMO

Orange juice (OJ) is among the most consumed fruit juices worldwide, and its chemopreventive action is fairly addressed in the literature. This review critically presents the available evidence linking OJ with cancer chemoprevention and on discussing the putative mechanisms and negative health effects. The chemopreventive action of OJ is related to its effect on metabolic enzymes and its antiinflammatory, cytoprotective/apoptotic, hormonal, cell signaling-modulating, antioxidant, and antigenotoxic effects. Most studies on OJ are in vitro, and few are conducted in vivo. Results from in vitro studies must be interpreted carefully because these findings do not consider in vivo bioavailability. However, such results are useful for studying the impact of different processing and storage methods on OJ's chemopreventive effect. Evidence of OJ's chemoprevention in humans is limited. OJ is antimutagenic in bacteria and antigenotoxic in humans and rodents. Studies using rodent cancer models showed that OJ is cancer chemopreventive, influencing either the induction stage or the promotion stage. The composition and, therefore, the chemopreventive action of OJ might be influenced by different cultivars, climates, extraction methods, packaging, storage temperatures, and shelf lives, among other factors. Epidemiological studies and randomized controlled intervention studies in humans evaluating the chemopreventive effect of OJ, taking into consideration variability in OJ composition, are needed.


Assuntos
Bebidas/análise , Quimioprevenção , Citrus/química , Frutas/química , Neoplasias/prevenção & controle , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citoproteção , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Fitoestrógenos/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
J Toxicol Environ Health A ; 76(6): 381-90, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23557236

RESUMO

Arrabidaea chica Verlot (Bignoniaceae) is an important folk medicine plant native to the Amazon region and used to treat anemia, hemorrhage, inflammation, intestinal colic, hepatitis, and skin affections. Although studies showed its therapeutic properties, little knowledge regarding genotoxic properties of this plant is available. The aim of this study was to determine the potential mutagenic and genotoxic/antigenotoxic effects of an A. chica chloroformic fraction (Ac-CF) obtained from leaves containing bioactive metabolites. The mutagenic effects were evaluated using the Salmonella mutagenicity assay, with TA98, TA97a, TA100, TA102, and TA1535 strains, with and without metabolic activation. In vivo mutagenic and genotoxic/antigenotoxic effects were investigated using the micronucleus (MN) test in bone marrow and alkaline comet assay in blood and liver after administration of 100, 500, or 1000 mg/kg Ac-CF in CF-1 mice by gavage (once a day for 3 d). In vitro antioxidant potential was evaluated using DPPH and xanthine/hypoxanthine assays. Ac-CF was not mutagenic in any of the Salmonella typhimurium strains tested and showed negative responses for mutagenicity and genotoxicity in mice. Further, Ac-CF displayed antigenotoxic effects by decreasing the oxidative DNA damage induced by hydrogen peroxide by greater than 50% in blood and liver. The antioxidant action detected in the in vitro assays demonstrated IC50 of 0.838 mg/ml in the xanthine/hypoxanthine assay and IC50 of 28.17 µg/ml in the DPPH assay. In conclusion, Ac-CF did not induce mutagenic and genotoxic effects and was able to protect DNA against oxidative damage in vivo, suggesting that this fraction may not pose genetic risks, although further toxicology assays are necessary.


Assuntos
Antioxidantes/toxicidade , Bignoniaceae/química , Medicina Tradicional , Mutagênicos/toxicidade , Extratos Vegetais/toxicidade , Plantas Medicinais/química , Administração Oral , Animais , Antioxidantes/classificação , Antioxidantes/metabolismo , Biotransformação , Células da Medula Óssea/efeitos dos fármacos , Ensaio Cometa , DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/análise , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mutagênicos/classificação , Mutagênicos/metabolismo , Extratos Vegetais/classificação , Extratos Vegetais/metabolismo , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
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