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1.
Comp Biochem Physiol C Toxicol Pharmacol ; 283: 109960, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885749

RESUMO

Pesticides used in rice cultivation can cause negative health effects to non-target organisms representative of natural biodiversity. In this context, the present study aimed to investigate the occurrence of pesticides in surface waters from a river that flows in the middle of a rice farming-dominated area. We were also interested in evaluate biochemical and histological effects caused by exposure (16 d) to the lower and higher concentrations of the main found herbicide (bentazone, BTZ), insecticide (chlorantraniliprole, CTP) and fungicide (tebuconazole, TBZ), isolated or mixed, in Boana faber tadpoles. No significant differences were observed in the development of the animals. Tadpoles exposed to the herbicide BTZ showed higher hepatic levels of malondialdehyde (MDA). In animals exposed to CTP, MDA levels were lower than controls. Animals exposed to the fungicide TBZ showed higher hepatic activity of glutathione S-transferase and carboxylesterase (CbE), as well as higher levels of carbonyl proteins and MDA. Animals exposed to Mix showed higher activity in CbE and glucose-6-phosphate dehydrogenase activity in the liver, as well as higher levels of MDA. In the brain and muscle of tadpoles exposed to Mix, acetylcholinesterase activity was higher. Histological changes were also observed in pesticide-exposed animals, such as increased occurrence of melanomacrophages, inflammatory infiltrates and congestion. Our data evidences the contamination of natural aquatic environments by rice pesticides, and the adverse effects of main ones in B. faber tadpoles, which suggests the contribution of pesticides derived from rice cultivation to the degradation of local biodiversity health.

2.
Aquat Toxicol ; 273: 106978, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38870676

RESUMO

Pesticides are released into the environment daily, and their effects on nontarget species in aquatic ecosystems have been widely reported. To evaluate the adverse effects caused in adults of Danio rerio species exposed to the pesticides abamectin, difenoconazole, and their commercial formulations (Kraft 36EC® and Score 250EC®), both isolated and in mixtures, biochemical biomarkers were analyzed in the gills of organisms exposed to sublethal concentrations. To this end, the activities of the enzymes 7-ethoxyresorufin-O-deethylase (EROD), glucuronosyltransferase (UDPGT), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), lipid hydroperoxide (LH), and malondialdehyde (MDA), which are indicative of oxidative stress, were measured after 48 h of exposure to the different pesticide treatments. The results showed a significant increase in EROD activity and MDA levels in the gills of fish exposed to the commercial formulation of abamectin. When the fish were exposed to difenoconazole and its commercial formulation, an increase in GST, GPx, and MDA levels and a decrease in GR activity were observed in the gills. Furthermore, the responses of the biomarkers were more pronounced in organisms exposed to mixtures of both active ingredients and commercial formulations. It is concluded that the commercial formulations Kraft 36EC® and Score 250EC® and their mixtures cause significant alterations in the detoxification metabolism of exposed organisms and induce oxidative stress in fish.

3.
Gene ; 927: 148722, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914244

RESUMO

Products from stingless bees are rich reservoirs of microbial diversity, including yeasts with fermentative potential. Previously, two Saccharomyces cerevisiae strains, JP14 and IP9, were isolated from Jataí (Tetragonisca angustula) and Iraí (Nannotrigona testaceicornis) bees, respectively, aiming at mead production. Both strains presented great osmotic and sulfite tolerance, and ethanol production, although they have a high free amino nitrogen demand. Herein, their genomes were sequenced, assembled, and annotated, and the variants were compared to the S. cerevisiae S288c reference strain. The final assembly of IP9 and JP14 presented high N50 and BUSCO scores, and more than 6430 protein-coding genes. Additionally, nQuire predicted the ploidy of IP9 as diploid, but the results were not enough to determine the ploidy of JP14. The mitochondrial genomes of IP9 and JP14 presented the same gene content as S288c but the genes were rearranged and fragmented in different patterns. Meanwhile, the genes with mutations of high impact (e.g., indels, gain of stop codon) for both yeasts were enriched for transmembrane transport, electron transfer, oxidoreductase, heme binding, fructose, mannose, and glucose transport, activities related to the respiratory chain and sugar metabolism. The IP9 strain presented copy number gains in genes related to sugar transport and cell morphogenesis; in JP14, genes were enriched for disaccharide metabolism and transport, response to reactive oxygen species, and polyamine transport. On the other hand, IP9 presented copy number losses related to disaccharide, thiamine, and aldehyde metabolism, while JP14 presented depletions related to disaccharide, oligosaccharide, asparagine, and aspartate metabolism. Notably, both strains presented a killer toxin gene, annotated from the assembling of unmapped reads, representing a potential mechanism for the control of other microorganisms population in the environment. Therefore, the annotated genomes of JP14 and IP9 presented a high selective pressure for sugar and nitrogen metabolism and stress response, consistent with their isolation source and fermentative properties.

4.
Aquat Toxicol ; 268: 106869, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38387247

RESUMO

Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.


Assuntos
Prednisolona , Poluentes Químicos da Água , Animais , Larva , Prednisona/metabolismo , Prednisona/farmacologia , Prednisolona/toxicidade , Prednisolona/metabolismo , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo
5.
Environ Pollut ; 341: 122900, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952920

RESUMO

Tebuconazole (TBZ) and azoxystrobin (AZX) are fungicides frequently used in rice cultivation. Despite protecting crops against fungal diseases, these compounds can contaminate the natural environments close to the crops, exerting negative effects on non-target organisms, the present study aimed to characterize the contamination by fungicides of a river that flows in an area dominated by rice cultivation in the north of the state of Santa Catarina, SC, Brazil. Concentrations of TBZ and AZX found in the field were used to evaluate their negative effects on development, biochemical biomarkers and histopatology of the liver of a native tadpole species, the hammerfrog (Boana faber). Tadpoles were exposed for 16 days to the lowest (1.20 µg/L) and highest (2.60 µg/L) concentration of TBZ, lowest (0.70 µg/L) and highest (1.60 µg/L) concentration of AZX, and the mix of both fungicides at lowest and highest concentration of each found in field analyses. Exposure to the lower TBZ concentration and both concentrations of the Mix accelerated the development of tadpoles. AZX caused an increase in the activities of glutathione S-transferase (GST), carboxylesterase (CbE) and glucose-6-phosphate dehydrogenase (G6PDH) in the liver, an increase in the levels of protein carbonyls (PC) in the liver and an increase in the activity of acetylcholinesterase (AChE) in muscle of tadpoles. TBZ, on the other hand, generated an increase in GST, G6PDH, PC and histopathological severity scores in liver and in muscle AChE activity. The effects were more intense in the groups exposed to the Mix of contaminants. No treatment altered brain AChE. The data showed that the fungicides from in rice cultivation found in natural aquatic environments around the crops pose risks to the health of the animals, compromising their metabolism and development.


Assuntos
Fungicidas Industriais , Oryza , Poluentes Químicos da Água , Animais , Fungicidas Industriais/toxicidade , Acetilcolinesterase , Produtos Agrícolas , Glutationa Transferase , Poluentes Químicos da Água/toxicidade , Larva
6.
Mar Pollut Bull ; 195: 115559, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37738876

RESUMO

This study aimed to assess the combined effect of hypoxia and exposure to diesel on biochemical parameters of Perna perna mussels. Mussels previously kept for 48 h in clean seawater were submitted to hypoxia for 24 h followed by reoxygenation in clean seawater for 48 h. The same procedure was done but using seawater containing 0.01 mL/L of diesel, before and after hypoxia. Antioxidant enzymes as well as levels of glutathione and lipid peroxidation were measured in gills and digestive glands. The neutral red retention time assay was also evaluated in hemocytes. Results showed that cycles of air exposure and reoxygenation caused oxidative stress and antioxidant modulation in both the gills and digestive glands. The presence of diesel in water triggered additional modulation of antioxidants under hypoxia and reoxygenation stress, apparently enhancing the capacity of mussels to avoid lipid peroxidation.

7.
Environ Monit Assess ; 195(6): 784, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261565

RESUMO

Land cover changes threaten biodiversity and alter the geographic distribution of forests worldwide. Studies on this topic are important to establish conservation strategies and public policies. However, different studies may propose different spatial representations due to differences when identifying, classifying, and/or mapping the same vegetation formation, as observed for the Cocais Forest region. This palm-dominated ecosystem predominates the Brazilian mid-north region in an ecotone region with 3 of the 6 Brazilian biomes. In this study, we conducted a literature review of studies that delineated and mapped the Cocais Forest, aiming to compare different mapped regions and to establish a new distribution map integrating these spatial data. We found seven sources that revealed spatial divergences in identifying the spatial distribution of Cocais Forest, including its characteristics in terms of size and shape, which could affect the conservation, socioeconomic, and cultural policies and studies carried out on this emblematic vegetation formation and influence area. The delineation proposed by de Sousa Nascimento and Lima (Revista de Políticas Públicas 189-192, 2016) encompassed the largest area. In addition, there was a lack of consensus regarding the nomenclature for this ecosystem, and few works offered a detailed description of the mapping process. Despite the different spatial distributions found for the Cocais Forest, we succeeded in establishing a common area by overlapping individual maps, resulting in the identification of a core region exclusive located in the State of Maranhão.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Florestas , Biodiversidade , Árvores
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 296: 122677, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37030253

RESUMO

Three new complexes Na[Ln(pic)4]ּ⋅2.5H2O (Ln = Tb, Eu or Gd; pic = picolinate) were synthesized and characterized by infrared spectroscopy, powder X-ray diffraction and thermogravimetric analyses. The molecular structures of the complexes have been determined by single-crystal X-ray diffraction. The three isostructural lanthanide complexes crystalize in the hexagonal system with space group P6122 to Eu complex and Gd complex and space group P6522 to Tb complex. In each of the complexes, the picolinate ligands are bonded to Ln3+ and Na+ ions by different coordination modes promoting polymeric structures. The photoluminescent properties of complexes were studied and combined with theoretical studies using the density functional theory (DFT: B3LYP, PBE1PBE) and the semiempirical method AM1/Sparkle from the single crystal X-ray diffraction structures to assign a suitable model for describing the system. The B3LYP DFT functional was considered the most adequate for providing structural properties of the compounds and for describing luminescence properties. The excited triplet states (T1) and excited singlet states (S1) of the ligand were determined theoretically using Time-dependent DFT calculations (TD-DFT: B3LYP, CAM-B3LYP and LC-wPBE) and INDO/S-CIS, with the best agreement with experimental values obtained from the LC-wPBE DFT functional. The photoluminescent spectra of the complexes and their lifetime measurements were determined indicating that the Eu complex and Tb complex display different intramolecular energy transfer mechanisms with higher efficiency to ligand-to-terbium energy transfer. In addition, the experimental and theorical Judd-Ofelt intensity parameters and quantum yields of the complexes were also determined and discussed besides to a proposed 9-state diagram to describe the luminescence properties of the Eu complex. The low value of emission quantum efficiency of 5D0 emitting level of Eu(III) ion was explained by the presence of the ligand-to-metal charge transfer state (LMCT) evidenced experimentally and theoretically. A good agreement was obtained between the proposed kinetic model and experimental results showing the consistency of the set of rate equations assumed and the intramolecular pathways proposed.

10.
Aquat Toxicol ; 257: 106468, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36870175

RESUMO

The influence of temperature (25 and 32 °C) on the biomarker responses of bullfrog tadpoles (Lithobates catesbeianus) to different concentrations of the atrazine metabolite 2-hydroxyatrazine (2-HA, 0, 10, 50 and 200 ng.L-1, 16 days), was evaluated. Temperature affected the activities of superoxide dismutase, glutathione S-transferase and acetylcholinesterase. The activities of catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and carboxylesterase presented no alterations. Frequencies of micronuclei and nuclear abnormalities were also not altered. 2-HA decreased SOD activity at 25 °C and caused histopathological changes in the liver and the kidney at both temperatures, with the kidney being more affected by the combination of higher temperature and 2-HA exposure, presenting glomerular shrinkage and an increase in Bowman's space. Our results indicate that at environmentally relevant concentrations, 2-HA can cause changes in biomarker responses as well as in the morphology of liver and kidney in L. catesbeianus tadpoles. Temperature has an important influence on biomarker response and histopathological alterations.


Assuntos
Atrazina , Poluentes Químicos da Água , Animais , Rana catesbeiana , Atrazina/metabolismo , Larva/metabolismo , Temperatura , Acetilcolinesterase/metabolismo , Poluentes Químicos da Água/toxicidade , Biomarcadores/metabolismo
12.
Food Chem ; 412: 135548, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-36738531

RESUMO

The purpose of this research was to evaluate performance of an energy-dispersive X-ray fluorescence (XRF) sensor to classify soybean based on protein content. The hypothesis was that sulfur signals and other XRF spectral features can be used as proxies to infer soybean protein content. Sample preparation and equipment settings to optimize detection of S and other specific emission lines were tested for this application. A logistic regression model for classifying soybean as high- or low-protein was developed based on XRF spectra and protein contents. Additionally, the model was validated with an independent set of samples. Global accuracies of the method were 0.83 (training set) and 0.81 (test set) and the corresponding kappa indices were 0.66 and 0.61, respectively. These numbers indicated satisfactory performance of the sensor, suggesting that XRF spectral features can be applied for screening protein content in soybean.


Assuntos
Glycine max , Espectrometria por Raios X/métodos , Raios X
13.
Ann Diagn Pathol ; 64: 152129, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36822052

RESUMO

INTRODUCTION: According to the World Health Organization's classification of endocrine tumors, papillary thyroid carcinoma (PTC) accounts for almost 90 % of malignant thyroid neoplasms. This study aimed to create a point system based on cytomorphological criteria for evaluating FNA products from thyroid nodules to predict the risk of papillary thyroid carcinomas. METHODS: This was an analytical observational study based on a retrospective analysis of cytological reports and surgical specimens from January 1, 2016, to December 31, 2021. Cytological slides were analyzed using the following ten variables: Nuclear Grooves; Intranuclear Pseudoinclusion; Cellularity; Colloid (Quantity); Clarified Chromatin; Overlapping nuclei; Irregular Nuclear Membrane; Multinucleated Giant Cells; Psamoma bodies; and Papillae. We categorized these variables quantitatively from zero to three points as follows: zero (absent), one (mild), two (moderate), and three (intense). RESULTS: Cytologies of 254 (4.9 %) cases were analyzed. The cut-off point was defined in this study as 6 ± 1 points. For the prediction of cases in benign, values < 5 points, malignant, values > 7 points and indeterminate, 5-7 points. Among the benign, there were 64 (69.5 %) cases <5 points, 17 (18.4 %) from 5 to 7 points and 11 (11.9 %) >7 points. Among the malignant ones, there were 12 (8.6 %) cases <5 points, 19 (13.6 %) from 5 to 7 points and 108 (77.6) >7 points. CONCLUSION: In this context, through the quantitative analysis of the ten suggested cytological variables, scored from 0 to 3, a final score > 7 is suspicious for malignancy, while a score < 5 is related to benign lesions.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/patologia , Biópsia por Agulha Fina , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico
15.
Adv Pharm Bull ; 13(1): 160-169, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36721806

RESUMO

Purpose: Breast cancer is the most common female malignancy and melanoma is the most lethal type of skin cancer. Traditional therapy for cancer treatment is far from satisfactory due to drug resistance and side effects, thus a search for new medicines is being emphasized. Palladium(II) complexes have been reported as anticancer potential agents. In this work, the anticancer activities and cell death induction of a new series of square-planar Pd(II) complexes were evaluated against MCF-7 and MDA-MB-435 cancer cells. Methods: MCF-7 (breast carcinoma) and MDA-MB-435 (melanoma) cells were cultivated, and treated with ligand and Pd(II) complexes. Cell growth, migration and adhesion inhibition, morphological alterations, cell death induction and, DNA interaction upon treatment were studied. Results: Pd(II) complexes exhibited both short and long-term antiproliferative effects on both cell lines, reducing by 80% cell growth in the SRB assay and abolishing longterm proliferation, estimated by the clonogenic assay. Complexes reduced significantly (P<0.05) cell migration and adhesion when compared to the control group. Complexes induced morphological alterations in cell lines and significant (P<0.05) cellular shrinkage. Cell death was induced and the complexes were able to interact with DNA, inducing cleavage of double-stranded DNA, which may account for the complexes cytotoxic effects, observed against both MCF-7 and MDA-MB-435 cells. Conclusion: Overall, the complexes exhibited cytotoxic activities and induced cell death. These observations emphasize an anticancer role with a potential therapeutic value for Pd(II) complexes to improve the outcome of patients with breast cancer and melanoma.

16.
Environ Pollut ; 322: 121159, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36716946

RESUMO

Thyroid hormones (TH) are essential for the metamorphosis of amphibians and their production can be influenced by environmental stressors, such as temperature fluctuations, and exposure to aquatic pollutants, such as herbicides. In the present study we evaluated the influence of different temperatures (25 and 32 °C) on the effects of the herbicide ametryn (AMT, 0 - control, 10, 50 and 200 ng.L-1) for 16 days on thyroidogenesis of bullfrog tadpoles. Higher temperature and AMT exposure caused a delay in the development of tadpoles, despite no differences were noted in weight gain and total length of the animals. Levels of triiodothyronine (T3) and thyroxine (T4) were not altered neither by AMT nor by temperature, but the highest temperature caused a decrease in total area and number of follicles in the thyroid gland. Transcript levels of thyroid hormone receptors alpha and beta (TRα and TRß) and iodothyronine deiodinase 3 (DIO3) were lower at 32 °C, which is consistent with developmental delay at the higher temperature. Tadpoles exposed to 200 ng.L-1 of AMT at 25 °C also presented delayed development, which was consistent with lower TRα and DIO3 transcript levels. Lower levels of estradiol were noted in tadpoles exposed to AMT at the higher temperature, being also possibly related to a developmental delay. This study demonstrates that higher temperature and AMT exposure impair thyroidgenesis in bullfrog tadpoles, disrupting metamorphosis.


Assuntos
Herbicidas , Animais , Rana catesbeiana , Larva , Herbicidas/toxicidade , Temperatura , Metamorfose Biológica
17.
J Exp Zool A Ecol Integr Physiol ; 339(2): 138-152, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36216792

RESUMO

γ-aminobutyric acid (GABA) is one of the main neurotransmitters involved in the adaptation processes against the damage that hypoxia can cause to the brain. Due to its antagonist action on GABA receptors, the insecticide fipronil can turn the fish more susceptible to the negative effects of hypoxia. This study aimed to understand better if fipronil affects these GABAergic responses of Tilapia ahead to hypoxia. Oreochromis Niloticus (Nile Tilapia) were exposed for 3 and 8 h to fipronil (0.0, 0.1, and 0.5 µg.L-1 ) under normoxia (dissolved O2 > 6 mg.L-1 ) and moderate hypoxia (dissolved O2 < 2 mg.L-1 ) conditions. Briefly, hypoxia caused opposite effects on the gene transcription of the evaluated ionotropic and metabotropic GABA receptors. Unexpectedly, we obtained reduced HIF1A mRNA and brain GABA levels, mostly in the first 3 h of the experiment, for the hypoxic group compared with the normoxia one. Besides that, we also demonstrated that the insecticide fipronil impairs the brain GABAergic signaling of a hypoxia-tolerant fish during the transition from a normoxic to an acute hypoxic state. Thus, these results predict the relevant impact on the brain metabolic adaptations of fishes exposed to such stressful conditions in an aquatic environment, as well as the effects of fipronil in the GABAergic responses to hypoxia, which in turn may have ecological and physiological significance to hypoxia-tolerant fishes exposed to this insecticide.


Assuntos
Ciclídeos , Inseticidas , Animais , Inseticidas/toxicidade , Hipóxia/metabolismo , Encéfalo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia , Receptores de GABA/genética , Receptores de GABA/metabolismo
18.
Biometals ; 36(1): 49-66, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36282444

RESUMO

This study, performed during 2003-2005 and 2008-2009, investigated metals (Al, Fe, Ba, Zn, Mn, Cr, Cu, Ni, Cd) content in seston at Cabo Frio Bay, SE-Brazil. This study may serve as a baseline of seston metal distribution to guide biogeochemical and ecological models. The seston fractions (> 20 µm, > 64 µm, > 100 µm, and > 150 µm) were sampled in sub-surface horizontal hauls. Metals were determined by ICP-MS. The metals range: Al (62.5-56,867.6 µg g-1), Fe (23.5-25,384.0 µg g-1), Mn (2.7-336.8 µg g-1), Ba (< 0.005-356.3 µg g-1), Zn (0.5-94.2 µg g-1), Cr (0.7-35.5 µg g-1), Cu (4.3-41.7 µg g-1), Ni (< 0.005-19.1 µg g-1) and Cd (< 0.0004-2.4 µg g-1). Aluminium, Fe, Mn, Ba, and Zn showed significant differences (p < 0.05) between the seston fraction. The results obtained in this study suggest that the elements (Fe, Mn, Ba) in the seston were strongly influenced by the abiogenic source. In contrast, Zn, Cd, Cu, Cr, and Ni can be biogenic/anthropogenic sources. The significant positive linear correlation of Zn:P, Cd:P, and Cu:P can indicate an intracellular concentration higher than the external adsorption in the plankton community.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Baías , Brasil , Cádmio , Monitoramento Ambiental/métodos , Metais
19.
Genes (Basel) ; 13(12)2022 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-36553603

RESUMO

Melatonin (MEL) presents well-documented pleiotropic actions against oxidative stress (OS), acting indirectly through activation of transcription factors, e.g., FoxO3 and Nrf2. Thus, this study aimed to investigate the possible modulating effects of MEL on the redox signaling pathways PI3K/AKT/FoxO3 and Keap1/Nrf2/ARE in K562 erythroleukemic cells subjected to OS induction. For this, the viability, and transcript levels of genes involved in redox adaptation were evaluated in K562 cells in different periods of erythroid differentiation: under OS induction by hydrogen peroxide (100 µM H2O2); treated with 1 nM (C1) and 1 mM (C2) MEL; and associated or not with stress induction. We observed a restoration of physiological levels of Nrf2 in both MEL concentrations under OS. The C1 was related to enhanced expression of antioxidant and proteasome genes through the Nrf2-ARE pathway, while C2 to the induction of FOXO3 expression, suggesting an involvement with apoptotic pathway, according to BIM transcript levels. The effects of MEL administration in these cells showed a period and dose-dependent pattern against induced-OS, with direct and indirect actions through different pathways of cellular adaptation, reinforcing the importance of this indolamine in the regulation of cellular homeostasis, being a promising therapeutic alternative for diseases that present an exacerbated OS.


Assuntos
Melatonina , Humanos , Melatonina/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Células K562 , Peróxido de Hidrogênio/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Oxirredução
20.
Genes (Basel) ; 13(12)2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36553634

RESUMO

This study aimed to establish the importance of ergothioneine (ERT) in the erythroid adaptation mechanisms by appraising the expression levels of redox-related genes associated with the PI3K/AKT/FoxO3 and Nrf2-ARE pathways using K562 cells induced to erythroid differentiation and H2O2-oxidative stress. Cell viability and gene expression were evaluated. Two concentrations of ERT were assessed, 1 nM (C1) and 100 µM (C2), with and without stress induction (100 µM H2O2). Assessments were made in three periods of the cellular differentiation process (D0, D2, and D4). The C1 treatment promoted the induction of FOXO3 (D0 and 2), PSMB5, and 6 expressions (D4); C1 + H2O2 treatment showed the highest levels of NRF2 transcripts, KEAP1 (D0), YWHAQ (D2 and 4), PSMB5 (D2) and PSMB6 (D4); and C2 + H2O2 (D2) an increase in FOXO3 and MST1 expression, with a decrease of YWHAQ and NRF2 was observed. in C2 + H2O2 (D2) an increase in FOXO3 and MST1, with a decrease in YWHAQ and NRF2 was observed All ERT treatments increased gamma-globin expression. Statistical multivariate analyzes highlighted that the Nrf2-ARE pathway presented a greater contribution in the production of PRDX1, SOD1, CAT, and PSBM5 mRNAs, whereas the PI3K/AKT/FoxO3 pathway was associated with the PRDX2 and TRX transcripts. In conclusion, ERT presented a cytoprotective action through Nrf2 and FoxO3, with the latter seeming to contribute to erythroid proliferation/differentiation.


Assuntos
Ergotioneína , Humanos , Ergotioneína/farmacologia , Ergotioneína/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Células K562 , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Oxirredução , Expressão Gênica
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