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1.
Molecules ; 26(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443417

RESUMO

Sambucus nigra flowers (elderflower) have been widely used in traditional medicine for the relief of early symptoms of common cold. Its chemical composition mainly consists of polyphenolic compounds such as flavonoids, hydroxycinnamic acids, and triterpenes. Although the antioxidant properties of polyphenols are well known, the aim of this study is to assess the antioxidant and protective potentials of Sambucus nigra flowers in the human neuroblastoma (SH-SY5Y) cell line using different in vitro approaches. The antioxidant capacity is first evaluated by the oxygen radical absorbance capacity (ORAC) and the free radical scavenging activity (DPPH) methods. Cell viability is assessed by the crystal violet method; furthermore, the intracellular ROS formation (DCFH-DA method) is determined, together with the effect on the cell antioxidant defenses: reduced glutathione (GSH) and antioxidant enzyme activities (GPx, GR). On the other hand, mTORC1 hyperactivation and autophagy blockage have been associated with an increase in the formation of protein aggregates, this promoting the transference and expansion of neurodegenerative diseases. Then, the ability of Sambucus nigra flowers in the regulation of mTORC1 signaling activity and the reduction in oxidative stress through the activation of autophagy/mitophagy flux is also examined. In this regard, search for different molecules with a potential inhibitory effect on mTORC1 activation could have multiple positive effects either in the molecular pathogenic events and/or in the progression of several diseases including neurodegenerative ones.


Assuntos
Técnicas de Cultura de Células , Degeneração Neural/tratamento farmacológico , Sambucus nigra/química , Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Compostos de Bifenilo/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Flores/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Degeneração Neural/patologia , Picratos/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Nat Commun ; 12(1): 5103, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429409

RESUMO

Hypercholesterolemia and dyslipidemia are associated with an increased risk for many cancer types and with poor outcomes in patients with established disease. Whereas the mechanisms by which this occurs are multifactorial we determine that chronic exposure of cells to 27-hydroxycholesterol (27HC), an abundant circulating cholesterol metabolite, selects for cells that exhibit increased cellular uptake and/or lipid biosynthesis. These cells exhibit substantially increased tumorigenic and metastatic capacity. Notably, the metabolic stress imposed upon cells by the accumulated lipids requires sustained expression of GPX4, a negative regulator of ferroptotic cell death. We show that resistance to ferroptosis is a feature of metastatic cells and further demonstrate that GPX4 knockdown attenuates the enhanced tumorigenic and metastatic activity of 27HC resistant cells. These findings highlight the general importance of ferroptosis in tumor growth and metastasis and suggest that dyslipidemia/hypercholesterolemia impacts cancer pathogenesis by selecting for cells that are resistant to ferroptotic cell death.


Assuntos
Colesterol/metabolismo , Ferroptose/fisiologia , Homeostase , Metabolismo dos Lipídeos , Neoplasias/metabolismo , Animais , Neoplasias da Mama , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Glutationa Peroxidase/metabolismo , Humanos , Hidroxicolesteróis , Neoplasias Pulmonares , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Metástase Neoplásica , Neoplasias/genética , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Molecules ; 26(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299505

RESUMO

Ebselen is the leader of selenorganic compounds, and starting from its identification as mimetic of the key antioxidant enzyme glutathione peroxidase, several papers have appeared in literature claiming its biological activities. It was the subject of several clinical trials and it is currently in clinical evaluation for the treatment of COVID-19 patients. Given our interest in the synthesis and pharmacological evaluation of selenorganic derivatives with this review, we aimed to collect all the papers focused on the biological evaluation of ebselen and its close analogues, covering the timeline between 2016 and most of 2021. Our analysis evidences that, even if it lacks specificity when tested in vitro, being able to bind to every reactive cysteine, it proved to be always well tolerated in vivo, exerting no sign of toxicity whatever the administered doses. Besides, looking at the literature, we realized that no review article dealing with the synthetic approaches for the construction of the benzo[d][1,2]-selenazol-3(2H)-one scaffold is available; thus, a section of the present review article is completely devoted to this specific topic.


Assuntos
Azóis/química , Azóis/síntese química , Azóis/farmacologia , Compostos Organosselênicos/química , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Antivirais/farmacologia , Biomimética/métodos , Inibidores de Ciclo-Oxigenase/farmacologia , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/farmacologia , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Selênio/química , Selenoproteínas/síntese química , Selenoproteínas/farmacologia
4.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299253

RESUMO

Pentathiepins are polysulfur-containing compounds that exert antiproliferative and cytotoxic activity in cancer cells, induce oxidative stress and apoptosis, and inhibit glutathione peroxidase (GPx1). This renders them promising candidates for anticancer drug development. However, the biological effects and how they intertwine have not yet been systematically assessed in diverse cancer cell lines. In this study, six novel pentathiepins were synthesized to suit particular requirements such as fluorescent properties or improved water solubility. Structural elucidation by X-ray crystallography was successful for three derivatives. All six underwent extensive biological evaluation in 14 human cancer cell lines. These studies included investigating the inhibition of GPx1 and cell proliferation, cytotoxicity, and the induction of ROS and DNA strand breaks. Furthermore, selected hallmarks of apoptosis and the impact on cell cycle progression were studied. All six pentathiepins exerted high cytotoxic and antiproliferative activity, while five also strongly inhibited GPx1. There is a clear connection between the potential to provoke oxidative stress and damage to DNA in the form of single- and double-strand breaks. Additionally, these studies support apoptosis but not ferroptosis as the mechanism of cell death in some of the cell lines. As the various pentathiepins give rise to different biological responses, modulation of the biological effects depends on the distinct chemical structures fused to the sulfur ring. This may allow for an optimization of the anticancer activity of pentathiepins in the future.


Assuntos
Glutationa Peroxidase/antagonistas & inibidores , Tiepinas/química , Tiepinas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
5.
Molecules ; 26(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202230

RESUMO

Prediabetes (PrDM) is a prodromal stage of diabetes mellitus (DM) with an increasing prevalence worldwide. During DM progression, individuals gradually develop complications in various organs. However, lungs are suggested to be affected later than other organs, such as the eyes, heart or brain. In this work, we studied the effects of PrDM on male Wistar rats' lungs and whether the regular consumption of white tea (WTEA) for 2 months contributes to the improvement of the antioxidant profile of this tissue, namely through improved activity of the first line defense antioxidant enzymes, the total antioxidant capacity and the damages caused in proteins, lipids and histone H2A. Our data shows that PrDM induced a decrease in lung superoxide dismutase and glutathione peroxidase activities and histone H2A levels and an increase in protein nitration and lipid peroxidation. Remarkably, the regular WTEA intake improved lung antioxidant enzymes activity and total antioxidant capacity and re-established the values of protein nitration, lipid peroxidation and histone H2A. Overall, this is the first time that lung is reported as a major target for PrDM. Moreover, it is also the first report showing that WTEA possesses relevant chemical properties against PrDM-induced lung dysfunction.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estado Pré-Diabético/metabolismo , Chá/química , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Glutationa Peroxidase/metabolismo , Histonas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Extratos Vegetais/química , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
6.
Nutrients ; 13(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207090

RESUMO

Nutrients consumed by mothers during pregnancy and lactation can exert permanent effects upon infant developing tissues, which could represent an important risk factor for diseases during adulthood. One of the important nutrients that contributes to regulating the cell cycle and tissue development and functionality is the trace element selenium (Se). Maternal Se requirements increase during gestation and lactation. Se performs its biological action by forming part of 25 selenoproteins, most of which have antioxidant properties, such as glutathione peroxidases (GPxs) and selenoprotein P (SELENOP). These are also related to endocrine regulation, appetite, growth and energy homeostasis. In experimental studies, it has been found that low dietary maternal Se supply leads to an important oxidative disruption in dams and in their progeny. This oxidative stress deeply affects gestational parameters, and leads to intrauterine growth retardation and abnormal development of tissues, which is related to endocrine metabolic imbalance. Childhood pathologies related to oxidative stress during pregnancy and/or lactation, leading to metabolic programing disorders like fetal alcohol spectrum disorders (FASD), have been associated with a low maternal Se status and intrauterine growth retardation. In this context, Se supplementation therapy to alcoholic dams avoids growth retardation, hepatic oxidation and improves gestational and breastfeeding parameters in FASD pups. This review is focused on the important role that Se plays during intrauterine and breastfeeding development, in order to highlight it as a marker and/or a nutritional strategy to avoid diverse fetal programming disorders related to oxidative stress.


Assuntos
Desenvolvimento Fetal , Estado Nutricional , Estresse Oxidativo , Selênio/análise , Animais , Antioxidantes , Feminino , Fertilidade , Transtornos do Espectro Alcoólico Fetal , Glutationa Peroxidase/metabolismo , Homeostase , Lactação , Fígado/metabolismo , Doenças Metabólicas , Oxirredução , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fatores de Risco , Selênio/deficiência , Selenoproteína P/metabolismo , Selenoproteínas/metabolismo
7.
Chem Biol Interact ; 347: 109601, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34324854

RESUMO

Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 µg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 µg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent: SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.


Assuntos
Aterosclerose/etiologia , Nanopartículas/toxicidade , Selênio/toxicidade , Animais , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa Peroxidase/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/patologia , Efeitos Adversos de Longa Duração , Masculino , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Selênio/administração & dosagem , Selênio/química , Tiorredoxina Redutase 1/metabolismo , Tiorredoxina Redutase 2/metabolismo
8.
Croat Med J ; 62(3): 215-226, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34212558

RESUMO

AIM: To determine the effects of metformin or liraglutide on oxidative stress level and antioxidative enzymes gene expression and activity in the blood and vessels of pre-diabetic obese elderly Sprague-Dawley (SD) rats of both sexes. METHODS: Male and female SD rats were assigned to the following groups: a) control group (fed with standard rodent chow); b) high-fat and high-carbohydrate diet (HSHFD) group fed with HSHFD from 20-65 weeks of age; c) HSHFD+metformin treatment (50 mg/kg/d s.c.); and d) HSHFD+liraglutide treatment (0.3 mg/kg/d s.c). Oxidative stress parameters (ferric reducing ability of plasma and thiobarbituric acid reactive substances) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and gene expression were determined from serum, aortas, and surface brain blood vessels (BBV). RESULTS: HSHFD increased body weight in both sexes compared with the control group, while liraglutide prevented this increase. Blood glucose level did not change. The liraglutide group had a significantly increased antioxidative capacity compared with the HSHFD group in both sexes. The changes in antioxidative enzymes' activities in plasma were more pronounced in male groups. The changes in antioxidative gene expression were more prominent in microvessels and may be attributed to weight gain prevention. CONCLUSIONS: Obesity and antidiabetic drugs caused sex-related differences in the level of antioxidative parameters. Liraglutide exhibited stronger antioxidative effects than metformin. These results indicate that weight gain due to HSHFD is crucial for developing oxidative stress and for inhibiting antioxidative protective mechanisms.


Assuntos
Metformina , Estado Pré-Diabético , Animais , Antioxidantes , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Liraglutida/farmacologia , Masculino , Metformina/farmacologia , Obesidade/tratamento farmacológico , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Caracteres Sexuais , Superóxido Dismutase/metabolismo
9.
Biomed Pharmacother ; 140: 111797, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34098193

RESUMO

Sodium Thiosulfate (STS) is already reported as an antioxidant, anti-inflammatory agent with antiseptic, antifungal properties. The search for an ideal antiseptic still continues, which is lethal to all types of bacteria and their spores and sustain the activity for a longer time without any harm to the host tissue. The aim of the present study is to evaluate the effect of STS on curing of wounds in rats when compared to Betadine. We developed topical gels having 6% and 12% STS. The effects of STS on wound healing rate of Rats were evaluated against Betadine as positive control. Wounds of control group, selected as Group 1 was treated with normal saline (0.2 ml), twice a day. Reference standard control, designated as Group 2 rats were given with 0.2 ml Betadine twice a day. Rats in Groups 3 and 4 were treated with 0.2 ml of STS gel (6% or 12% respectively) twice a day. In our study, STS formulation has proved to be a safe and efficient wound healing product. It has a neutral pH and longer half life (>12 months). Higher STS dose of 12% proved to have a wound curing rate equivalent to that of Betadine. On 11th Day, 97 ± 0.79% healing was achieved with Betadine and 98 ± 0.67% with 12% STS Gel (∗P < 0.05). Microscopic images of H&E stained skin tissue from animals treated with Betadine and 12% STS formulation showed a reduction in scar size, lesser amount of inflammatory cells, higher fibroblasts and blood vessels, with considerable collagen accumulation. Furthermore, a significant enhancement in the levels of GPx, CAT and SOD was observed in the tissue at the wound site of the treated group. The IL 10 levels in both groups of STS-treated rats was increased, whereas, TNF-α levels were reduced significantly in tissue homogenate compared with control. Thus, this study shows the wound-healing performance of STS formulation. Further studies are necessary to understand the real mechanism of how STS formulation heals wounds.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Tiossulfatos/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Catalase/metabolismo , Géis , Glutationa Peroxidase/metabolismo , Interleucina-10/metabolismo , Masculino , Povidona-Iodo/uso terapêutico , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
J Med Chem ; 64(13): 9166-9181, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34132541

RESUMO

Timely myocardial reperfusion salvages ischemic myocardium from infarction, whereas reperfusion itself induces cardiomyocyte death, which is called myocardial ischemia/reperfusion (MI/R) injury. Herein, ß-carboline derivative 17c was designed and synthesized with obvious myocardial protective activity for the first time. Pretreatment of 17c effectively protected the cardiomyocyte H9c2 cells from H2O2-induced lactate dehydrogenase leakage and restored the endogenous antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Besides, 17c effectively protected the mitochondria through decreasing the reactive oxygen species overproduction and enhancing the mitochondrial membrane potential. As a result, 17c significantly reduced the necrosis of cardiomyocytes in H2O2-induced oxidative stress, which was more potent than polydatin. In MI/R injury rats, 17c pretreatment obviously increased the levels of SOD and GSH-Px and inhibited the apoptosis of cardiomyocytes. Through this way, the size of myocardial infarction was significantly reduced after MI/R injury in vivo, better than that of polydatin, suggesting that 17c is a promising cardioprotectant for the prevention of MI/R injury.


Assuntos
Carbolinas/farmacologia , Descoberta de Drogas , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Masculino , Estrutura Molecular , Traumatismo por Reperfusão Miocárdica/induzido quimicamente , Traumatismo por Reperfusão Miocárdica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Superóxido Dismutase/metabolismo
11.
Toxicology ; 458: 152836, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34147545

RESUMO

China's clean energy and resources are mainly located in the west and north while electric load center is concentrated in the middle and east. Thus, these resources and energy need to be converted into electrical energy in situ and transported to electric load center through ultra-high voltage direct current (UHVDC) transmissions. China has built 25,000 km UHVDC transmission lines of 800 kV and 1100 kV, near which the impact of electric field on health has attracted public attention. Previous studies showed that time-varying electromagnetic field exposure could disturb testosterone secretion. To study the effect of non-time-varying electric field caused by direct current transmission lines on testosterone synthesis, male ICR mice were continually (24 h/d) exposed to static electric field of 56.3 ± 1.4 kV/m. Results showed that on the 3rd day of exposure and on the 7th day after ceasing the exposure of 28 d, serum testosterone level and testicular oxidative stress indicators didn't change significantly. On the 28th day of exposure, serum testosterone levels, testicular glutathione peroxidase (GSH-Px) activity, the mRNA and protein levels of testicular StAR, PBR, CYP11A1 decreased significantly, and testicular malondialdehyde (MDA) content increased significantly. Meanwhile, electron-dense edges and vacuolation appeared in lipid droplets of Leydig cells. The gap between inner mitochondrial membrane (IMM) and outer mitochondrial membrane (OMM) enlarged, which would cause the swelling of mitochondria, the rupture and deficiency of mitochondrial membranes. Analysis showed that testicular oxidative stress could induce the damage of mitochondrial structure in Leydig cells, which would decrease the rate of cholesterol transport from cytoplasm to mitochondria. Since cholesterol is the necessary precursor of testosterone synthesis, testosterone synthesis was inhibited. The decrease of the mRNA and protein expression levels of StAR and PBR in testes could diminish the cholesterol transported from OMM to IMM. The decrease of the mRNA and protein expression levels of CYP11A1 could reduce the pregnenolone required in testosterone synthesis and inhibit testosterone synthesis consequently.


Assuntos
Campos Eletromagnéticos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/efeitos da radiação , Testosterona/biossíntese , Animais , Antioxidantes/metabolismo , Colesterol/metabolismo , Citoplasma/metabolismo , Citoplasma/efeitos da radiação , Glutationa Peroxidase/metabolismo , Células Intersticiais do Testículo/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos ICR , Membranas Mitocondriais/metabolismo , Membranas Mitocondriais/efeitos da radiação , Dilatação Mitocondrial/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Fosfoproteínas/metabolismo , Testosterona/sangue , Vacúolos/efeitos da radiação , Vacúolos/ultraestrutura
12.
Mar Environ Res ; 169: 105383, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34116384

RESUMO

The activities of the key antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP) and glutathione reductase (GR) as well as levels of reduced glutathione (GSH) and integral antioxidant activity (IAA), were studied in the digestive glands and gills of 14 bivalve species. Species and tissue differences of the antioxidant (AO) systems of the investigated mollusks were discussed in connection with their physiological and biochemical peculiarities. This article describes the role of the AO system of mollusks in adaptation to natural habitat conditions and shows the relationship of AO activity with the maximum habitat depth (MHD) and maximum lifespan (MLS) of these species.


Assuntos
Antioxidantes , Bivalves , Animais , Bivalves/metabolismo , Catalase/metabolismo , Ecossistema , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo
13.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070944

RESUMO

Embryogenesis is a complex multi-stage process regulated by various signaling molecules including pineal and extrapineal melatonin (MT). Extrapineal MT is found in the placenta and ovaries, where it carries out local hormonal regulation. MT is necessary for normal development of oocytes, fertilization and subsequent development of human, animal and avian embryos. This review discusses the role of MT as a regulator of preimplantation development of the embryo and its implantation into endometrial tissue, followed by histo-, morpho- and organogenesis. MT possesses pronounced antioxidant properties and helps to protect the embryo from oxidative stress by regulating the expression of the NFE2L2, SOD1, and GPX1 genes. MT activates the expression of the ErbB1, ErbB4, GJA1, POU5F1, and Nanog genes which are necessary for embryo implantation and blastocyst growth. MT induces the expression of vascular endothelial growth factor (VEGF) and its type 1 receptor (VEGF-R1) in the ovaries, activating angiogenesis. Given the increased difficulties in successful fertilization and embryogenesis with age, it is of note that MT slows down ovarian aging by increasing the transcription of sirtuins. MT administration to patients suffering from infertility demonstrates an increase in the effectiveness of in vitro fertilization. Thus, MT may be viewed as a key factor in embryogenesis regulation, including having utility in the management of infertility.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Melatonina/uso terapêutico , Ovário/metabolismo , Placenta/metabolismo , Animais , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Feminino , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Infertilidade Feminina/genética , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Infertilidade Feminina/prevenção & controle , Melatonina/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ovário/crescimento & desenvolvimento , Glândula Pineal/crescimento & desenvolvimento , Glândula Pineal/metabolismo , Gravidez , Receptor ErbB-4/genética , Receptor ErbB-4/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Molecules ; 26(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067571

RESUMO

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 µg/mL) or N-Acetyl-L-cysteine (NAC) (20 µM) for 24 h, and then incubated with 200 µM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 µM) or PCs (4, 8 or 16 µg/mL) in the absence or presence of 300 µM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.


Assuntos
Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Acetilcisteína/farmacologia , Animais , Elementos de Resposta Antioxidante , Antioxidantes/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator de Transcrição NF-E2/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/metabolismo
15.
Mol Immunol ; 135: 388-397, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022514

RESUMO

Heat stress-induced decline in milk production and mammary glands dysfunction are economically important challenges facing the dairy industry, especially in summer. Choline is an organic water-soluble compound that can regulate a series of vital biological process, including cellular structural integrity and oxidative stress. However, it is unclear whether choline plays an anti-apoptosis and antioxidant effect in heat stress-induced mammary epithelial cells. This study aimed to determine the antioxidant effect of choline on heat stress-induced apoptosis and oxidative stress and its underlying molecular mechanism in bovine mammary epithelial cells (MAC-T cells). The MAC-T cells were divided into four treatment groups: control (37℃), choline (37℃), heat stress (HS, 42℃), and HS + choline. The results showed that heat stress up-regulated the HSP70 and HSP90 expression both in mRNA and protein, enhanced ROS accumulation, increased malondialdehyde (MDA) content, reduced the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, significantly increased the expression of caspase-3 and upregulated the ratio of Bax/Bcl-2 and ultimately lead to oxidative stress and apoptosis in MAC-T cells. However, choline pretreatment reversed the above phenomenon compared with the HS group. The HS + choline group inhibited heat stress-induced phosphorylation of PERK, nuclear translocation of Nrf-2 and the protein expression of GRP78. In addition, the ratio of Bax/Bcl-2 and the expression of caspase-3 were significantly reduced in HS + choline group, thereby reduced the HS-induced oxidative stress and apoptosis in MAC-T cells. In conclusion, choline attenuates heat stress-induced oxidative stress and apoptosis of MAC-T cells by modulating PERK/Nrf-2 pathway.


Assuntos
Apoptose/efeitos dos fármacos , Colina/farmacologia , Resposta ao Choque Térmico/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , eIF-2 Quinase/metabolismo , Animais , Antioxidantes/farmacologia , Caspase 3/metabolismo , Bovinos , Linhagem Celular , Células Epiteliais/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP72/biossíntese , Proteínas de Choque Térmico HSP90/biossíntese , Proteínas de Choque Térmico/metabolismo , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Linfócitos T/efeitos dos fármacos
16.
Biomed Pharmacother ; 139: 111627, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33965728

RESUMO

Lipids excess from an uterine environment can increase free radicals production of and thus induce oxidative status imbalance, a key factor for progression of non-alcoholic fatty liver disease (NAFLD) in offspring. Food antioxidant components in maternal diet may play an important role in preventing offspring metabolic disorders. The objective of the study was to evaluate the effects of açaí pulp supplementation on maternal high-fat diet, by assessing activity and expression of antioxidant enzymes and biomarkers of oxidative stress in the liver. Female Fisher rats were divided into four groups and fed a control diet (C), a high-fat diet (HF), a control diet supplemented with açaí (CA) and a high-fat diet supplemented with açaí (HFA) before mating, during gestation and lactation. The effects of açaí supplementation on oxidative stress biomarkers and antioxidant enzymes expression were evaluated in dams and male offspring after weaning. HFA diet increased body weight in dams, however reduced absolute and relative liver weight. There was a reduction in liver biomarkers of oxidative stress, malondialdehyde and carbonyl protein, as well as in catalase, glutathione peroxidase and superoxide dismutase activity. In offspring, HFA diet reduced liver weight and increased Gpx1, Gpx4 and Sod1 mRNA expression. These results suggest that açaí is able to restore redox status, preventing oxidative damage in dams by a direct mechanism and to promote beneficial effects on expression of antioxidant defences related genes in offspring.


Assuntos
Antioxidantes/metabolismo , Euterpe/química , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Suplementos Nutricionais , Feminino , Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Lactação , Fígado/efeitos dos fármacos , Fígado/enzimologia , Camundongos , Hepatopatia Gordurosa não Alcoólica , Tamanho do Órgão/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Gravidez , Ratos , Ratos Endogâmicos F344 , Superóxido Dismutase-1/metabolismo
17.
FASEB J ; 35(6): e21550, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33960023

RESUMO

Species have evolved unique mechanisms to combat the effects of oxidative stress inside cells. A particularly devastating consequence of an unhindered oxidation of membrane lipids in the presence of iron results in cell death, known as ferroptosis. Hallmarks of ferroptosis, including peroxidation of polyunsaturated fatty acids, are conserved among animals and plants, however, early divergence of an ancestral mammalian GPX4 (mGPX4) has complicated our understanding of mechanistic similarities between species. To this end, we performed a comprehensive phylogenetic analysis and identified that orthologous Arabidopsis GPXs (AtGPXs) are more highly related to mGPX4 than mGPX4 is to other mammalian GPXs. This high degree of conservation suggested that experimental substitution may be possible. We, therefore, ectopically expressed AtGPX1-8 in ferroptosis-sensitive mouse fibroblasts. This substitution experiment revealed highest protection against ferroptosis induction by AtGPX5, as well as moderate protection by AtGPX2, -7, and -8. Further analysis of these cells revealed substantial abatement of lipid peroxidation in response to pharmacological challenge. The results suggest that the presence of ancestral GPX4 resulted in later functional divergence and specialization of GPXs in plants. The results also challenge a strict requirement for selenocysteine activity and suggest thioredoxin as a potent parallel antioxidant system in both plants and mammals.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Evolução Biológica , Ferroptose , Fibroblastos/citologia , Glutationa Peroxidase/metabolismo , Animais , Proteínas de Arabidopsis/genética , Morte Celular , Fibroblastos/metabolismo , Glutationa Peroxidase/genética , Células HeLa , Humanos , Camundongos , Oxirredução , Estresse Oxidativo , Filogenia
18.
Fish Shellfish Immunol ; 114: 199-206, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33940173

RESUMO

Co-infection with parasites and bacteria is of frequent occurrence in aquaculture, leads to growth impedance otherwise mortality in fish depending on the varying degree of a load of primary pathogen either parasite or bacteria. The mechanistic regulation of immune response during co-infection in fish has merely documented. The aim of this study was to determine the impact of co-infection with Aeromonas hydrophila at three exposure doses of Argulus sp. on the innate immune responses and antioxidative stress enzymes of goldfish (Carassius auratus). The experimental fish were randomly distributed into eight treatment groups viz. T1 (control group without Argulus and A. hydrophila infection), T2 (fish exposed to a sub-lethal dose of A. hydrophila), T3 (low Argulus-infested fish), T4 (T3 + sub-lethal dose of A. hydrophila), T5 (moderate Argulus-infested fish), T6 (T5 + sub-lethal dose of A. hydrophila), T7 (high Argulus-infested fish) and T8 (T7+ sub-lethal dose of A. hydrophila) in duplicates. After distributing experimental fish into their respective treatment group, A. hydrophila was injected to T2, T4, T6 and T8. After the bacterial challenge, four fish from each experimental group were randomly sampled on 24, 72, and 168 h and subjected to the hematological, innate immune parameters and enzymatic analysis. In the co-infection group T8, a high degree of enhanced pathogenicity of A. hydrophila was noticed with increased mortalities (84.2%) in comparison to other groups. The current study shows a declining pattern in RBC, PCV and Hb values with the degree of parasite infestation without co-infection groups. Moreover, in the T8 group, exposure of a sub-lethal dose of bacteria resulted in a drastic reduction of the recorded parameters. Furthermore, a decreased value for WBC, monocyte and neutrophil was found in higher parasite group co-infected with a sub-lethal dose of bacteria relative to other co-infected groups during the experimental period. Also, a decrease in innate immune parameters and antioxidative stress enzymes were observed in the T8 group compared to T7 and T2 groups throughout the trial period. These findings indicate that a rise in the dose of Argulus infection improves A. hydrophila colonization in goldfish and contributes to suppression of the innate immune system and increased mortality.


Assuntos
Aeromonas hydrophila , Arguloida , Carpa Dourada , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata/fisiologia , Doenças Parasitárias em Animais/parasitologia , Animais , Antioxidantes , Catalase/genética , Catalase/metabolismo , Regulação Enzimológica da Expressão Gênica/imunologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Infecções por Bactérias Gram-Negativas/complicações , Infecções por Bactérias Gram-Negativas/imunologia , Doenças Parasitárias em Animais/complicações , Doenças Parasitárias em Animais/imunologia , Estresse Fisiológico , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 259: 119891, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33984715

RESUMO

As primary industrial raw material, the widespread usage of bisphenol A (BPA) has resulted in sustained release and accumulation in the environment. Besides its endocrine-disrupting character, BPA was reported to generate excessive reactive oxygen species (ROS). However, the potential toxic mechanisms of the BPA-induced oxidative damage to plants were poorly understood. In this study, glutathione peroxidase 6 from Arabidopsis thaliana (AtGPX6) was regarded as biomarker to investigate the toxic effects of BPA on plants by multi-spectroscopic techniques and molecular docking method. Firstly, BPA effectively quenched the intrinsic fluorescence of AtGPX6 via static quenching mechanism, and a single binding site of AtGPX6 towards BPA was presumed. Moreover, the binding force was mainly driven by van der Waals forces and hydrogen bonding based on the negative values of ΔH0 and ΔS0, which was consistent with the molecular docking result. In addition, the conformational changes of AtGPX6 accompanied with the enhancement of the hydrophilicity around the tryptophan residues upon the combination with BPA, were evaluated through the combination of the fluorescence, UV-visible absorption and Circular dichroism (CD) spectroscopy. Finally, the inhibitory impact on the development of Arabidopsis seedling roots was observed under BPA exposure. Therefore, the exploration of the molecular mechanism of AtGPX6 with BPA would provide valuable assessments on the toxic effects of BPA on plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Arabidopsis/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Simulação de Acoplamento Molecular
20.
Wiad Lek ; 74(3 cz 1): 535-538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813464

RESUMO

OBJECTIVE: The aim: To increase the effectiveness of treatment of sinusitis polyposa patients, develop and introduce a new non-traditional complex method of influencing several links of the pathogenesis of this disease, including laser therapy and laser puncture, used in the postoperative period. PATIENTS AND METHODS: Materials and methods: In 60 rhinosinusitis polyposa patients the indicators of lipid peroxidation and the state of antioxidant protection were studied. Depending on the type of treatment, the patients were divided into two groups: the first included 30 people who underwent traditional surgical intervention, and the second - 30 people who used complex therapy, including in the postoperative period endonasal laser exposure and laser puncture. Methods: clinical data, the functional state of the nasal mucosa, indicators of lipid peroxidation (hydroperoxide, malondialdehyde) and antioxidant activity (glutathione peroxidase, glutathione reductase, reduced glutathione, superoxide cismutase, catalase) of erythrocyte membranes and blood serum were studied. RESULTS: Results: The proposed complex method for treating lipids of erythrocyte membranes and serum, which includes endonasal surgical intervention, endonasal laser therapy and laser puncture leads to the normalization of physiological functions of the nose, activates antioxidant protection and reduces the peroxide activity of lipids in the membranes of erythrocytes and blood serum. CONCLUSION: Conclusions: When examining patients in the long-term (after 1 year) period, a significant improvement in 85.7% of cases, an improvement in 10.7%, and absence of effect in 3.6% was achieved. Thus, the proposed method of therapy can be recommended for widespread use in medical institutions.


Assuntos
Sinusite , Superóxido Dismutase , Antioxidantes , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Peroxidação de Lipídeos , Sinusite/terapia , Superóxido Dismutase/metabolismo
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