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1.
Anticancer Res ; 39(9): 4795-4803, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519581

RESUMO

BACKGROUND/AIM: To determine the mechanism of vitamin D3-induced modulation of antioxidant-related factors in endometrial cancer, we investigated their role in apoptosis of human endometrial cancer cells exposed to vitamin D3 Materials and Methods: The survival rate of human endometrial cancer cells was estimated after treatment with activated vitamin D3 Reactive oxygen species (ROS) levels were measured using flow cytometry. The levels of VDR, Trx, TXNIP and apoptosis-related proteins were investigated using western blotting and immunocytochemistry in human tissues. RESULTS: Treatment with D3 induced apoptotic cell death and cell-cycle arrest by increasing ROS concentration. Vitamin D3 inhibited proliferation of human endometrial cancer cells. It regulated intracellular ROS concentration in endometrial cancer cells via increased TXNIP expression. CONCLUSION: Antioxidant regulation via TXNIP is an important cell death mechanism in human endometrial cancer, and occurs via induction by vitamin D3.


Assuntos
Antioxidantes/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias do Endométrio/metabolismo , Tiorredoxinas/metabolismo , Vitamina D/análogos & derivados , Apoptose/efeitos dos fármacos , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Vitamina D/farmacologia
2.
Dokl Biochem Biophys ; 486(1): 197-200, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367820

RESUMO

The oxidative modification of human hemoglobin (Hb) treated with hydrogen peroxide was investigated. Using the mass spectrometry method, the oxidized amino acid residues of the hemoglobin molecule were detected: αTrp14, αTyr24, αArg31, αMet32, αTyr42, αHis45, αHis72, αMet76, αPro77, αLys90, αCys104, αTyr140, ßHis2, ßTrp15, ßTrp37, ßMet55, ßCys93, ßCys112, ßTyr130, ßLys144, and ßHis146. The antioxidant potential of the Hb molecule in the intracellular space and in the blood plasma is discussed.


Assuntos
Hemoglobinas/metabolismo , Peróxido de Hidrogênio/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
3.
BMC Plant Biol ; 19(1): 323, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319801

RESUMO

BACKGROUND: Exogenous 5-aminolevulinic acid (ALA) positively regulates plants chlorophyll synthesis and protects them against environmental stresses, although the protection mechanism is not fully clear. Here, we explored the effects of ALA on chlorophyll synthesis in tomato plants, which are sensitive to low temperature. We also examined the roles of the glutathione S-transferase (GSTU43) gene, which is involved in ALA-induced tolerance to oxidation stress and regulation of chlorophyll synthesis under low temperature. RESULTS: Exogenous ALA alleviated low temperature caused chlorophyll synthesis obstacle of uroporphyrinogen III (UROIII) conversion to protoporphyrin IX (Proto IX), and enhanced the production of chlorophyll and its precursors, including endogenous ALA, Proto IX, Mg-protoporphyrin IX (Mg-proto IX), and protochlorophyll (Pchl), under low temperature in tomato leaves. However, ALA did not regulate chlorophyll synthesis at the level of transcription. Notably, ALA up-regulated the GSTU43 gene and protein expression and increased GST activity. Silencing of GSTU43 with virus-induced gene silencing reduced the activities of GST, superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, and increased the membrane lipid peroxidation; while fed with ALA significant increased all these antioxidase activities and antioxidant contents, and alleviated the membrane damage. CONCLUSIONS: ALA triggered GST activity encoded by GSTU43, and increased tomato tolerance to low temperature-induced oxidative stress, perhaps with the assistance of ascorbate- and/or a glutathione-regenerating cycles, and actively regulated the plant redox homeostasis. This latter effect reduced the degree of membrane lipid peroxidation, which was essential for the coordinated synthesis of chlorophyll.


Assuntos
Ácido Aminolevulínico/metabolismo , Clorofila/metabolismo , Genes de Plantas/fisiologia , Glutationa Transferase/metabolismo , Lycopersicon esculentum/genética , Proteínas de Plantas/metabolismo , Ácido Aminolevulínico/farmacologia , Resposta ao Choque Frio , Glutationa Transferase/genética , Homeostase/efeitos dos fármacos , Peroxidação de Lipídeos , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/metabolismo , Lycopersicon esculentum/fisiologia , Oxirredução/efeitos dos fármacos , Proteínas de Plantas/genética
4.
Phys Chem Chem Phys ; 21(29): 16190-16197, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31298243

RESUMO

Over the past few years, the interest in Resveratrol (3,4',5,-trihydroxystilbene, RSV) has increased due to the evidence found of its antioxidant action that protects biomolecules and cells from oxidative damage. The interest has been further exacerbated by the natural presence of RSV in some fruits and derivatives, especially in red wine. In this paper we present evidence of RSV capacity in protecting a deoxynucleotide, an essential constituent of DNA, from one-electron oxidation. This article evaluates the mechanism responsible for the antioxidant action of RSV, after one-electron oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP), by kinetic analysis during steady-state irradiation and laser flash photolysis experiments. Results showed that RSV protects dGMP by recovering the nucleotide from its radical, which is formed after the reaction of dGMP with the triplet excited state of the photosensitizer. In the absence of RSV, dGMP is irremediably oxidized, and if the damage occurs in dGMP located in DNA molecules, the consequences can be as serious as mutations and subsequent carcinogenic lesions.


Assuntos
Guanina/química , Resveratrol/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Elétrons , Neoplasias/prevenção & controle , Oxirredução/efeitos dos fármacos , Resveratrol/química
5.
Life Sci ; 232: 116634, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279782

RESUMO

AIM: Here, we evaluated the possible protective effects of oleuropein, the major phenolic constituent in virgin olive oil against glycerol-induced acute kidney injury (AKI) in rats. MAIN METHODS: Twenty-eight Sprague Dawley rats were allocated equally into four groups as follows: control group, oleuropein group (50 mg/kg body weight), AKI group and the oleuropein + AKI group. AKI was induced by injecting 50% glycerol (10 ml/kg body weight) intramuscularly. KEY FINDINGS: Glycerol injection increased the kidney relative weight as well as rhabdomyolysis (RM)- and AKI-related index levels, including the levels of creatine kinase, lactate dehydrogenase, creatinine, urea, and Kim-1 expression. Additionally, alteration in oxidative conditions in renal tissue was recorded, as confirmed by the elevated malondialdehyde and nitric oxide levels and the decreased glutathione content. Concomitantly, the protein and mRNA expression levels of antioxidant enzymes were suppressed. Moreover, Nfe2l2 and Hmox1 mRNA expression was also downregulated. Glycerol triggered inflammatory reactions in renal tissue, as evidenced by the increased pro-inflammatory cytokines and Ccl2 protein and mRNA expression, whereas myeloperoxidase activity was increased. Furthermore, glycerol injection enhanced apoptotic events in renal tissue by increasing the expression of the pro-apoptotic proteins and decreasing that of anti-apoptotic. However, oleuropein administration reversed the molecular, biochemical, and histological alterations resulting from glycerol injection. SIGNIFICANCE: Our data suggest that oleuropein has potential as an alternative therapy to prevent or minimize RM incidence and subsequent development of AKI, possibly due to its potent anti-stress, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Iridoides/farmacologia , Lesão Renal Aguda/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Creatina Quinase/metabolismo , Creatinina/metabolismo , Glutationa/metabolismo , Glicerol/efeitos adversos , Glicerol/farmacologia , Inflamação/metabolismo , Iridoides/metabolismo , Rim/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Rabdomiólise/complicações
6.
Pestic Biochem Physiol ; 157: 211-218, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153471

RESUMO

Herbivore attack leads to enhanced production of defensive compounds to mount anti-herbivore defense in plants via activation of the jasmonate signaling pathway. On the other hand, some herbivores can eavesdrop on plants defense signaling and up-regulate their cytochrome P450 genes to increase detoxification of defensive compounds. However, the ecological risk of eavesdropping on plant defense signaling is largely unknown. In this study, we examined the induction of cytochrome P450s by methyl jasmonate (MeJA) and its consequence on the toxicity of aflatoxin B1 (AFB1) to Helicoverpa armigra larvae. The results show that MeJA applications either in a diet or volatile exposure enhanced the toxicity of AFB1 to the larvae. RNA sequences analysis revealed that cytochrome P450 CYP6AE19 was highly induced when MeJA was applied with AFB1. In addition, HaGST encoding glutathione-S-transferase that mainly transforms aflatoxin B1 exo-8,9-epoxide to aflatoxin B1 exo-8,9-glutathione was also induced. RNA interference of CYP6AE19 via injecting a double-stranded RNA decreased mortality of larvae exposed to AFB1; while injecting a double-stranded RNA of HaGST increased larval mortality. Furthermore, a protein model was generated and a subsequent docking simulation for AFB1 suggests the bioactivation as a major mechanism of AFB1. This study provides evidence that MeJA increased larval mortality of H. armigera via induction of CYP6AE19 that can bioactivate AFB1.


Assuntos
Acetatos/farmacologia , Aflatoxina B1/metabolismo , Ciclopentanos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Mariposas/efeitos dos fármacos , Mariposas/metabolismo , Oxilipinas/farmacologia , Animais , Larva/efeitos dos fármacos , Larva/metabolismo , Oxirredução/efeitos dos fármacos
7.
Pestic Biochem Physiol ; 157: 45-52, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31153476

RESUMO

Herein, we describe the enhanced antifungal activity of silver nanoparticles biosynthesized by cell free filtrate of Trichoderma viride (MTCC 5661) in comparison to chemically synthesized silver nanoparticles (CSNP) of similar shape and size. Biosynthesized silver nanoparticles (BSNP) enhanced the reduction in dry weight by 20 and 48.8% of fungal pathogens Fusarium oxysporum and Alternaria brassicicola respectively in comparison to their chemical counterparts (CSNP). Nitroblue tetrazolium and Propidium iodide staining demonstrated the higher generation of superoxide radicals lead to higher death in BSNP treated fungus in comparison to CSNP. Scanning electron microscopy of A. brassicicola revealed the osmotic imbalance and membrane disintegrity to be major cause for fungal cell death after treatment with BSNP. To gain an insight into the mechanistic aspect of enhanced fungal cell death after treatment of BSNP in comparison to CSNP, stress responses and real time PCR analysis was carried out with A. brassicicola. It revealed that generation of ROS, downregulation of antioxidant machinery and oxidative enzymes, disruption of osmotic balance and cellular integrity, and loss of virulence are the mechanisms employed by BSNP which establishes them as superior antifungal agent than their chemical counterparts. With increasing drug resistance and ubiquitous presence of fungal pathogens in plant kingdom, BSNP bears the candidature for new generation of antifungal agent.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Nanopartículas Metálicas/química , Doenças das Plantas/microbiologia , Prata/química , Alternaria/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
8.
Chem Biol Interact ; 310: 108728, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254498

RESUMO

Disruption of the mitochondrial function has been associated with redox impairment and triggering of cell death in nucleated human cells, as observed in several diseases. The administration of chemicals that would prevent mitochondrial dysfunction is an attractive strategy in cases of neurodegeneration, cardiovascular diseases, and metabolic disorders. Methylglyoxal (MG) is a dicarbonyl compound that exhibits an important role as a mitochondrial toxicant in neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease) and diabetes mellitus. On the other hand, naringenin (NGN; C15H12O5) is a natural antioxidant that also presents anti-inflammatory effects in mammalian cells. In this context, we have evaluated whether and how NGN would be able to prevent the mitochondria-related bioenergetics and redox dysfunctions induced by MG in the human neuroblastoma SH-SY5Y cells. The cells were pretreated (for 2 h) with NGN (at 10-80 µM) and then challenged with MG at 500 µM for 24 h. NGN significantly attenuated the effects of MG on the mitochondrial function and redox environment in this experimental model. Moreover, NGN prevented the MG-triggered mitochondria-related cell death in SH-SY5Y cells. Nonetheless, the inhibition of the synthesis of glutathione (GSH, a major non-enzymatic antioxidant) suppressed the promotion of mitochondrial protection by NGN in MG-treated cells. We also found that the synthesis of GSH was induced by NGN through a mechanism associated with the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Therefore, NGN caused mitochondrial protection by an Nrf2/GSH-dependent manner in SH-SY5Y cells exposed to MG.


Assuntos
Flavanonas/farmacologia , Glutationa/metabolismo , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Neuroblastoma/patologia , Fármacos Neuroprotetores/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Flavanonas/uso terapêutico , Humanos , Oxirredução/efeitos dos fármacos , Aldeído Pirúvico/efeitos adversos
9.
An Acad Bras Cienc ; 91(2): e20181373, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241709

RESUMO

Fabry disease (FD) is an X-linked inherited disease and occurs due to mutations in GLA gene that encodes the α-galactosidase enzyme. Consequently, there is an accumulation of enzyme substrates, namely globotriaosylceramide (GB3). FD is a multisystemic disease, caused by storage of GB3 in vascular endothelia, with significant renal, cardiac and vascular involvement. The aim of this work was to evaluate the in vitro effect of GB3 on electron transport chain complexes (ETC) and redox parameters. Biochemical biomarkers were determined in homogenates of cerebral cortex, kidneys and liver of Wistar rats in the presence or absence of GB3 at concentrations of 3, 6, 9 and 12 mg/L. We found that GB3 caused an increase of ETC complexes II and IV activities, increased production of reactive species and decreased superoxide dismutase enzyme activity in homogenates of cerebral cortex. As well also increased production of reactive species and superoxide dismutase activity in kidney homogenates. The results obtained in our work suggest that GB3 interferes in ETC complexes II and IV activities, however, the magnitude of this increase seems to be too low to present a physiologically importance. However, the imbalance in cellular redox state indicating that these alterations may be involved in the pathophysiology of FD, mainly in renal and cerebral manifestations.


Assuntos
Córtex Cerebral/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Doença de Fabry/metabolismo , Rim/metabolismo , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Triexosilceramidas/farmacologia , Animais , Modelos Animais de Doenças , Doença de Fabry/enzimologia , Masculino , Ratos , Ratos Wistar
10.
Gen Physiol Biophys ; 38(3): 237-244, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31184310

RESUMO

Hyperglycemia impairs oxidative capacity in skeletal muscle. Muscle oxidative capacity is regulated by peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). Transcutaneous carbon dioxide (CO2) enhances PGC-1α expression in skeletal muscle. Therefore, the aim of this study was to clarify the effects of CO2 therapy on muscle oxidative capacity impaired by streptozotocin (STZ)-induced hyperglycemia. Eight-week-old male Wistar rats were randomly divided into 4 groups: control, CO2 treatment, STZ-induced hyperglycemia, and STZ-induced hyperglycemia treated with CO2. STZ-induced hyperglycemia resulted in a decrease of muscle oxidative capacity and decreased PGC-1α and cytochrome c oxidase subunit 4 (COX-4) expression levels; while, application of transcutaneous CO2 attenuated this effect, and enhanced the expression levels of endothelial nitric oxide synthesis (eNOS). These results indicate that transcutaneous CO2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.


Assuntos
Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/farmacologia , Hiperglicemia/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Administração Cutânea , Animais , Modelos Animais de Doenças , Masculino , Oxirredução/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar
11.
Ultrason Sonochem ; 55: 57-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084791

RESUMO

The synthesis of nanoparticles often result in the generation of harmful chemical pollutants. As such, many researchers have focused on developing green processes, which include the biosynthesis. In this research, ZnO nanoparticles were prepared using the leaf extract of whortleberry (Vaccinium arctostaphylos L.) via a simple ultrasonic-assisted method. The morphology, crystal size and structure, surface, thermal, and optical properties of the bio-mediated ZnO sample (ZnOext) were analyzed and compared with that produced without incorporating the extract (ZnOchem). The ZnO samples were evaluated for their antidiabetic, antibacterial, as well as their sono- and photo-catalytic performances. Initially, the samples were intraperitoneal injected to alloxan-diabetic rats to examine their treatment efficiency in terms of effects on fasting blood glucose, insulin, cholesterol, high-density lipoprotein, and total triglyceride levels. The ZnOext showed significantly higher efficiency for improving the health status of alloxan-diabetic rats in contrast with other tested treatments, vis. ZnOchem, insulin, and only leaf extract. In addition, both the ZnO samples were assessed against gram-negative and gram-positive bacteria and through sono- and photo-catalytic processes for removing rhodamine B, respectively. The results of this study indicated that not only the ZnOext sample was pollution free, it also exhibited higher potentials for treating diabetic rats, bacterial decontamination, and also oxidative removal of organic compounds under the influences of ultrasound and UV irradiations when compared with ZnOchem sample.


Assuntos
Nanopartículas/química , Extratos Vegetais/química , Folhas de Planta/química , Ondas Ultrassônicas , Vaccinium/química , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Técnicas de Química Sintética , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Oxirredução/efeitos dos fármacos
12.
Acta Cir Bras ; 34(4): e201900404, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066786

RESUMO

PURPOSE: To examine the effect of taxifolin on I/R induced gastric injury in rats using biochemical and histopatholohical methods. METHODS: Eighteen albino Wistar male rats equally grouped as; gastric I/R (I/R), 50 mg/kg taxifolin + gastric I/R (TAX+ I/R) and sham operation applied (SHAM). Ischemia induced for 1 hour, and reperfusion induced for 3 hours. RESULTS: Oxidant parameters like, Malondialdehyde (MDA) and Hydroxyguanine (8-OHdG) were higher, whereas total glutathione (tGSH) was lower in the I/R group according to SHAM group, histopathological findings such as marked destruction, edema, and proliferated dilated congested blood vessels were observed severely in the I/R group, whereas there was not any pathological finding except mild dilated congested blood vessels in the TAX+ I/R group. CONCLUSION: The taxifolin can be clinically beneficial in the treatment of gastric injury due to I/R procedure.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Mucosa Gástrica/lesões , Quercetina/análogos & derivados , Traumatismo por Reperfusão/prevenção & controle , Animais , Artéria Celíaca/cirurgia , Modelos Animais de Doenças , Ligadura , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/uso terapêutico , Ratos , Ratos Wistar
13.
Molecules ; 24(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067700

RESUMO

A global approach that is based on a combination of mass spectrometry (MS) and nuclear magnetic resonance (NMR) data has been developed for a complete and rapid understanding of drug degradation mixtures. We proposed a workflow based on a sample preparation protocol that is compatible to MS and NMR, the selection of the most appropriate experiments for each technique, and the implementation of prediction software and multivariable analysis method for a better interpretation and correlation of MS and NMR spectra. We have demonstrated the efficient quantification of the remaining active pharmaceutical ingredient (API). The unambiguous characterization of degradation products (DPs) was reached while using the potential of ion mobility-mass spectrometry (IM-MS) for fragment ions filtering (HDMSE) and the implementation of two-dimensional (2D) NMR experiments with the non-uniform sampling (NUS) method. We have demonstrated the potential of quantitative NMR (qNMR) for the estimation of low level DPs. Finally, in order to simultaneously monitor multi-samples, the contribution of partial least squares (PLS) regression was evaluated. Our methodology was tested on three indapamide forced degradation conditions (acidic, basic, and oxidative) and it could be easily transposed in the drug development field to assist in the interpretation of complex mixtures (stability studies, impurities profiling, and biotransformation screening).


Assuntos
Desenvolvimento de Medicamentos , Estabilidade de Medicamentos , Indapamida/química , Cromatografia Líquida de Alta Pressão , Humanos , Indapamida/uso terapêutico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Oxirredução/efeitos dos fármacos
14.
Molecules ; 24(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052590

RESUMO

Type 2 diabetic patients possess a two to four fold-increased risk for Cardiovascular Diseases (CVD). Hyperglycemia, oxidative stress associated with endothelial dysfunction and dyslipidemia are regarded as pro-atherogenic mechanisms of CVD. In this study, high-fat diet-induced diabetic and non-diabetic vervet monkeys were treated with 90 mg/kg of aspalathin-rich green rooibos extract (Afriplex GRT) for 28 days, followed by a 1-month wash-out period. Supplementation showed improvements in both the intravenous glucose tolerance test (IVGTT) glycemic area under curve (AUC) and total cholesterol (due to a decrease of the low-density lipoprotein [LDL]) values in diabetics, while non-diabetic monkeys benefited from an increase in high-density lipoprotein (HDL) levels. No variation of plasma coenzyme Q10 (CoQ10) were found, suggesting that the LDL-lowering effect of Afriplex GRT could be related to its ability to modulate the mevalonate pathway differently from statins. Concerning the plasma oxidative status, a decrease in percentage of oxidized CoQ10 and circulating oxidized LDL (ox-LDL) levels after supplementation was observed in diabetics. Finally, the direct correlation between the amount of oxidized LDL and total LDL concentration, and the inverse correlation between ox-LDL and plasma CoQ10 levels, detected in the diabetic monkeys highlighted the potential cardiovascular protective role of green rooibos extract. Taken together, these findings suggest that Afriplex GRT could counteract hyperglycemia, oxidative stress and dyslipidemia, thereby lowering fundamental cardiovascular risk factors associated with diabetes.


Assuntos
Chalconas/farmacologia , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores , Glicemia/efeitos dos fármacos , Cercopithecus aethiops , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Lipídeos/sangue , Lipoproteínas LDL/sangue , Masculino , Extratos Vegetais/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/sangue
15.
Molecules ; 24(9)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086086

RESUMO

The wax apple (Syzygium samarangense) is traditionally employed as an antibacterial and immunostimulant drug in traditional medicine. This plant is rich in different flavonoids and tannins. In this study, we isolated two compounds from S. samarangense leaves: myricitrin and 3,5-di-O-methyl gossypetin. Then, we investigated the mechanisms of action of the two compounds against oxidative stress (induced by sodium arsenite) and inflammation (induced by UV light) on human keratinocytes. We could clearly demonstrate that the pre-treatment of cells with both compounds was able to mitigate the negative effects induced by oxidative stress, as no alteration in reactive oxygen species (ROS) production, glutathione (GSH) level, or protein oxidation was observed. Additionally, both compounds were able to modulate mitogen-activated protein kinase (MAPK) signaling pathways to counteract oxidative stress activation. Finally, we showed that 3,5-di-O-methyl gossypetin exerted its antioxidant activity through the nuclear transcription factor-2 (Nrf-2) pathway, stimulating the expression of antioxidant proteins, such as HO-1 and Mn-SOD-3.


Assuntos
Flavonoides/química , Flavonoides/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Syzygium/química , Antioxidantes/metabolismo , Linhagem Celular , Flavonoides/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
16.
Mediators Inflamm ; 2019: 7072917, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011285

RESUMO

Reactive oxidative species (ROS) are important inflammatory mediators. Electrons escaping from the mitochondrial electron transport chain (ETC) during oxidative phosphorylation (OXPHOS) in the mitochondrial respiratory chain (RC) complexes contribute to ROS production. The cellular antioxidant enzymes are important for maintaining ROS release at the physiological levels. It has been reported that BoHV-1 infection induces overproduction of ROS and oxidative mitochondrial dysfunction in cell cultures. In this study, we found that chemical interruption of RC complexes by TTFA (an inhibitor of RC complex II), NaN3 (an inhibitor of RC complex IV), and oligomycin A (an inhibitor of ATP synthase) consistently decreased virus productive infection, suggesting that the integral processes of RC complexes are important for the virus replication. The virus infection significantly increased the expression of subunit SDHB (succinate dehydrogenase) and MTCO1 (cytochrome c oxidase subunit I), critical components of RC complexes II and IV, respectively. The expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase (CAT), and glutathione peroxidase 4 (GPX4) was differentially affected following the virus infection. The protein TFAM (transcription factor A, mitochondrial) stimulated by either nuclear respiratory factor 1 (NRF1) or NRF2 is a key regulator of mitochondrial biogenesis. Interestingly, the virus infection at the late stage (at 16 h after infection) stimulated TFAM expression but decreased the levels of both NRF1 and NRF2, indicating that virus infection activated TFAM signaling independent of either NRF1 or NRF2. Overall, this study provided evidence that BoHV-1 infection altered the expression of molecules associated with RC complexes, antioxidant enzymes, and mitochondrial biogenesis-related signaling NRF1/NRF2/TFAM, which correlated with the previous report that virus infection induces ROS overproduction and mitochondrial dysfunction.


Assuntos
Antioxidantes/metabolismo , Herpesvirus Bovino 1/patogenicidade , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Western Blotting , Linhagem Celular , Cães , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Oligomicinas/farmacologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Azida Sódica/farmacologia , Succinato Desidrogenase/metabolismo , Tenoiltrifluoracetona/farmacologia
17.
Biosens Bioelectron ; 133: 160-168, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30933710

RESUMO

An efficient and new electrochemical biosensor for detection of DNA damage, induced by the interaction of the hybrid anti-cancer compound (7ESTAC01) with DNA, was studied by differential pulse voltammetry (DPV). The biosensor consists of a Stem-Loop DNA (SL-DNA) probe covalently attached to the gold electrode (GE) surface that hybridizes to a complementary DNA strand (cDNA) to form a double-stranded DNA (dsDNA). The interaction and DNA damage induced by 7ESTAC01 was electrochemically studied based on the oxidation signals of the electroactive nucleic acids on the surface of the GE by DPV. As a result, the SL-DNA/GE and dsDNA/GE were tested with the reduced 7ESTAC01, showing the voltammetric signal of guanine and adenine, increase in the presence of 7ESTAC01. Under optimum conditions, the dsDNA/GE biosensor exhibited excellent DPV response in the presence of 7ESTAC01. The bonding interaction between 7ESTAC01 and calf thymus DNA (ctDNA) was confirmed by UV-Vis absorption spectroscopy, dynamic simulations (performed to investigate the DNA structure under physiological conditions), and molecular docking. Theoretical results showed the presence of hydrogen bonding and intercalation in the minor groove of DNA, involving hydrophobic interactions.


Assuntos
Antineoplásicos/química , Técnicas Biossensoriais , DNA/isolamento & purificação , Técnicas Eletroquímicas , Antineoplásicos/farmacologia , DNA/química , DNA/genética , Dano ao DNA/efeitos dos fármacos , DNA Complementar/química , DNA Complementar/genética , Ouro/química , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Sequências Repetidas Invertidas/genética , Simulação de Acoplamento Molecular , Oxirredução/efeitos dos fármacos , Raios Ultravioleta
18.
Biomed Res Int ; 2019: 7127869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032360

RESUMO

Natural enzyme mimics have attracted considerable attention due to leakage of enzymes and their easy denaturation during their storage and immobilization procedure. Here in this study, for the first time, a new iron oxide hydroxide, ferrihydrite - Fe1.44O0.32 (OH) 3.68 magnetic nanoparticles were synthesized by bacterial strain named Comamonas testosteroni. The characterization of the produced magnetic nanoparticles was confirmed by transmission electron microscopy (TEM), Fourier-transform spectroscopy (FTIR), X-ray diffraction (XRD), and magnetization hysteresis loops. Further, these extracted nanoparticles were proven to have biogenic magnetic behavior and to exhibit enhanced peroxidase-like activity. It is capable of catalyzing the oxidation of 3, 3', 5, 5'-Tetramethylbenzidine (TMB) by H2O2 to produce blue color (typical color reactions). Catalysis was examined to follow Michaelis-Menton kinetics and the good affinity to both H2O2 and TMB. The K m value of the Fe1.44O0.32 (OH) 3.68 with H2O2 and TMB as the substrate was 0.0775 and 0.0155 mM, respectively, which were lower than that of the natural enzyme (HRP). Experiments of electron spin resonance (ESR) spectroscopy proved that the BMNPs could catalyze H2O2 to produce hydroxyl radicals. As a new peroxidase mimetic, the BMNPs were exhibited to offer a simple, sensitive, and selective colorimetric method for determination of H2O2 and glucose and efficiently catalyze the detection of glucose in real blood samples.


Assuntos
Comamonas testosteroni/química , Glucose/química , Peróxido de Hidrogênio/química , Peroxidase/química , Benzidinas/química , Biomimética , Técnicas Biossensoriais , Catálise , Espectroscopia de Ressonância de Spin Eletrônica , Compostos Férricos/síntese química , Compostos Férricos/química , Compostos Férricos/farmacologia , Glucose/isolamento & purificação , Peróxido de Hidrogênio/isolamento & purificação , Cinética , Nanopartículas de Magnetita , Microscopia Eletrônica de Transmissão , Oxirredução/efeitos dos fármacos , Peroxidase/síntese química , Peroxidase/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
19.
Int J Mol Sci ; 20(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995737

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by defective social communication and interaction and restricted, repetitive behavior with a complex, multifactorial etiology. Despite an increasing worldwide prevalence of ASD, there is currently no pharmacological cure to treat core symptoms of ASD. Clinical evidence and molecular data support the role of impaired mitochondrial fatty acid oxidation (FAO) in ASD. The recognition of defects in energy metabolism in ASD may be important for better understanding ASD and developing therapeutic intervention. The nuclear peroxisome proliferator-activated receptors (PPAR) α, δ, and γ are ligand-activated receptors with distinct physiological functions in regulating lipid and glucose metabolism, as well as inflammatory response. PPAR activation allows a coordinated up-regulation of numerous FAO enzymes, resulting in significant PPAR-driven increases in mitochondrial FAO flux. Resveratrol (RSV) is a polyphenolic compound which exhibits metabolic, antioxidant, and anti-inflammatory properties, pointing to possible applications in ASD therapeutics. In this study, we review the evidence for the existing links between ASD and impaired mitochondrial FAO and review the potential implications for regulation of mitochondrial FAO in ASD by PPAR activators, including RSV.


Assuntos
Antioxidantes/uso terapêutico , Transtorno do Espectro Autista/tratamento farmacológico , Ácidos Graxos/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Resveratrol/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Transtorno do Espectro Autista/metabolismo , Metabolismo Energético/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Terapia de Alvo Molecular/métodos , Oxirredução/efeitos dos fármacos , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos
20.
Methods Mol Biol ; 1977: 83-97, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30980324

RESUMO

Reduction and alkylation are common processing steps in sample preparation for qualitative and quantitative proteomic analyses. In principle, these steps mitigate the limitations resulting from the presence of disulfide bridges. There has been recurring debate in the proteomics community around their use, with concern over negative impacts that result from overalkylation (off-target, non-thiol sites) or incomplete reduction and/or S-alkylation of cysteine. This chapter integrates findings from a number of studies on different reduction and alkylation strategies, to guide users in experimental design for their optimal use in proteomic workflows.


Assuntos
Cisteína/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteômica , Alquilantes/farmacologia , Alquilação/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Proteômica/métodos , Substâncias Redutoras/farmacologia , Fluxo de Trabalho
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