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1.
Life Sci ; 246: 117400, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32032645

RESUMO

AIMS: Comparative sub-acute toxicity, including tolerance and dependence potential of fentanyl and its three novel and potent analogues was determined in mice. MAIN METHODS: Comparative sub-acute (21 d, intraperitoneal; 1/10 LD50) toxicity of fentanyl and its three novel analogues viz., N-(1-(2-phenoxyethyl)-4-piperidinyl) propionanilide (2), N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6) was determined in mice. Animals were observed for additional seven days to assess the recovery. The brain, liver and kidney toxicity was assessed on the basis of various biochemical, oxidative, histological, and neuroadaptive markers. The expression levels of key neuronal markers associated with drug tolerance and dependence were investigated by western blot and immunohistochemistry. KEY FINDINGS: Fentanyl and its analogues caused abnormal levels of liver and kidney specific biomarkers in plasma. Brain malondialdehyde (MDA) levels were raised by all the treatments and kidney MDA level by analogue 6 (21 d). Reduced glutathione levels in brain, liver, and kidney were diminished by all the treatments (21 & 28 d) and a significant change in the levels of antioxidant enzymes was also produced mainly after 21 d. The deleterious effects of fentanyl and its analogues were further substantiated by corresponding histopathological changes in brain, liver and kidney (21 & 28 d). These compounds were also found to produce neuroadaptive changes as evidenced by the increased expression levels of c-Fos, glucocorticoid receptor, N-methyl-d-aspartate receptor1 and µ-opioid receptor (21 & 28 d). SIGNIFICANCE: Three novel analogues of fentanyl were envisaged to have alternative therapeutic potentials. However, their comparative sub-acute toxicity revealed undesirable side effects, thereby masking their therapeutic ability.


Assuntos
Fentanila/toxicidade , Animais , Biomarcadores/análise , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dano ao DNA/efeitos dos fármacos , Fentanila/análogos & derivados , Glutationa/análise , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/análise , Camundongos , Estresse Oxidativo/efeitos dos fármacos
2.
Chem Commun (Camb) ; 56(4): 515-518, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31825409

RESUMO

Understanding GSH flux in developing neurons is prerequisite to reveal its role in neuronal development but necessiates an ultrasensitive assay. By systematically exploring key structural factors determing probe sensitivity in live cells, we developed a fluorogenic probe capable of imaging subtle GSH fluctuations in developing neurons.


Assuntos
Corantes Fluorescentes/análise , Glutationa/análise , Neurônios/metabolismo , Animais , Butionina Sulfoximina/farmacologia , Células Cultivadas , Corantes Fluorescentes/química , Glutationa/antagonistas & inibidores , Glutationa/metabolismo , Humanos , Camundongos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Imagem Óptica
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117403, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31344582

RESUMO

In this study, a water-soluble, near-infrared fluorescent probe (EQR-S) was designed for the measurement of the glutathione (GSH) concentration. Responses of different interfering substances to the developed probe were investigated, and the luminescence mechanism was examined by theoretical calculations. Results revealed that EQR-S can be applied for the rapid, sensitive determination of the GSH concentration with a detection limit of 69 nM. Based on the above advantages, EQR-S was successfully applied to investigate the fluctuation in the GSH concentration of living cells under high-temperature stress.


Assuntos
Técnicas Citológicas/métodos , Corantes Fluorescentes/química , Glutationa/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Corantes Fluorescentes/análise , Glutationa/química , Células Hep G2 , Humanos , Modelos Moleculares
4.
Talanta ; 207: 120294, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594563

RESUMO

Dual-functional nanosensors based on small molecule regulation can be widely used due to their simplicity, high sensitivity and selectivity. Herein, glutathione (GSH) calibrated dual-functional system for GSH and cadmium ions (Cd2+) detection based on fluorescence resonance energy transfer (FRET) between NH2-NaYF4:Yb,Er/NaYF4@SiO2 upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) is designed. Unmodified AuNPs are easy to aggregate in high-salt solution and thereby quenching the red emission of UCNPs. The presence of GSH prevents the aggregation of AuNPs, so GSH can be detected by the changes in the color of solution and the recovery of red emission of UCNPs. However, Cd2+ can interact with GSH, which makes AuNPs easy to aggregate, resulting in a gradual decrease in red emission of UCNPs. The fluorescence response of the system is linear with the concentrations of GSH and Cd2+ in a wide range of concentrations, with low detection limits of 0.016 µM and 0.059 µM, respectively. Furthermore, the nanosensor demonstrates high selectivity for GSH and Cd2+ detection and can be applied for the detection of GSH in human plasma and Cd2+ in drinking water.


Assuntos
Cádmio/análise , Transferência Ressonante de Energia de Fluorescência , Fluoretos/química , Glutationa/análise , Ouro/química , Nanopartículas Metálicas/química , Dióxido de Silício/química , Ítrio/química , Água Potável/química , Glutationa/sangue , Humanos
5.
J Food Sci ; 84(12): 3546-3554, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710090

RESUMO

Sparkling wines were elaborated with the nontraditional varieties Villenave, Niagara, Manzoni, and Goethe, and monitored in relation to the changes in phenolic composition, browning index, and glutathione content during 18 months of biological aging (sur lies). Important changes in the phenolic profile, browning index, and glutathione content were observed in the sparkling wines during the over-lees aging period. The major phenolic compound in the sparkling wines was tyrosol, followed by caffeic, trans-caftaric, and gallic acids, catechin and epicatechin. The biological aging led to an increase in the individual phenolic compounds, especially caffeic, gallic, and ellagic acids, and an increase in the browning index was also observed during the aging period. Caffeic acid was significantly correlated with browning and aging period in all sparkling wines, which indicates that this compound can be useful as a quality marker to monitoring the biological aging profile of white sparkling wines. The results obtained indicate that the aging period (sur lie) had an important influence on the changes in the unique phenolic profile of the sparkling wines elaborated with nontraditional varieties. PRACTICAL APPLICATION: In sparkling wines production, the secondary fermentation occurring in the sealed bottle during the vinification contributes greatly to their quality and sensory complexity. The Vitis labrusca and hybrid grapes varieties represent most of the grapes cultivated in Brazil being employed in the elaboration of juices and wines. These varieties present a great oenological potential and have not been explored yet regarding to the production of white sparkling wines. The use of these nontraditional grape varieties cultivated in South Brazil may be a viable alternative in the production of white sparkling wines with biological aging potential and particular bioactive properties.


Assuntos
Glutationa/análise , Polifenóis/química , Vitis/química , Vinho/análise , Brasil , Fermentação , Manipulação de Alimentos , Frutas/química , Fenóis/química , Fatores de Tempo , Vitis/classificação
6.
Bratisl Lek Listy ; 120(11): 843-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31747765

RESUMO

INTRODUCTION: The aim of this study is to investigate the effects of obstructive jaundice on the liver and effectivity of alpha­lipoic acid on liver damage and oxidative stress. MATERIALS AND METHODS: Thirty­six male Sprague­Dawley rats were divided into 3 groups per 12 animals, namely into Group I (control group): the bile duct was only mobilized by laparotomy, Group II (bile duct ligation group - BDL): the common bile duct was closed with clips and OJ was caused after laparotomy, and Group III (bile duct ligation and alpha­lipoic acid group - BDL+LA): after closing the common bile duct, LA was administered in an intramuscular dose of 50 mg/kg for 10 days. On the 10th day, malondialdehyde, glutathione and superoxide dismutase levels were measured in liver and histopathological evaluation was performed. RESULTS: AST (U/L)/ALT(U/L) in groups I, II and III were 155.33/51.83, 445.28/165.89, 380.78/173.33, respectively (p < 0.005). Superoxide dismutase and glutathione levels were lower in patient groups than in the control group (0.31 µl/g vs 0.36 µl/g; p < 0.05). After the lipoic acid treatment, none of the biochemical markers of liver improved. Only the increase in superoxide dismutase (0.31 µl/g and 0.34 µl/g in groups II and III, respectively) and glutathione levels (0.16 µl/g and 0.22 µl/g in groups II and III, respectively) was statistically significant (p < 0.05). CONCLUSIONS: Histopathological damage was statistically significantly decreased and antioxidant levels were statistically significantly increased after LA treatment (Tab. 1, Fig. 6, Ref. 23).


Assuntos
Icterícia Obstrutiva/tratamento farmacológico , Estresse Oxidativo , Ácido Tióctico/farmacologia , Animais , Antioxidantes/análise , Ductos Biliares , Glutationa/análise , Humanos , Ligadura , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/análise , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Superóxido Dismutase/análise
7.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 728-731, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726501

RESUMO

Objective: To observe the lung injury of male rats induced by sub-chronic exposure to crotonaldehyde, and to explore the possible mechanism of injury. Methods: Forty SPF male Wistar rats were randomly divided into control group and 3 groups in each group, and each group received 0.0, 2.5, 4.5, 8.5 mg/kg body weight crotonaldehyde solution for continuous intragastric administration. 120 d, once a day. After the end of the exposure, the body weight of the rats was measured, and the lung tissues were quickly separated after cervical dislocation. The organ coefficients were calculated and histopathological examination was performed to determine malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione. Peroxidase (GSH-Px) content; ELISA was used to measure interleukin (IL) -6, IL-1ß, and tumor necrosis factor (TNF) -α in lung tissues. Results: Compared with the control group, the weight gain of the rats in the 4.5 and 8.5 mg/kg exposure groups was small, and the lung weight and organ coefficient of the exposed group decreased, the difference was statistically significant (P<0.05). In the exposed group, the lung tissue structure was disordered, the alveolar wall was thickened, and inflammatory cell infiltration was observed. Compared with the control group, the MDA activity in the serum of the rats in the 4.5 mg/kg and 8.5 mg/kg groups increased, and the SOD and GSH-Px activities decreased, the difference was statistically significant (P<0.05). TNF-α levels in the lung tissues of rats exposed to 4.5 mg/kg and 8.5 mg/kg, and levels of (IL) -6 and IL-1ß in the lungs of rats in the 2.5, 4.5, and 8.5 mg/kg groups. Significantly increased, the difference was statistically significant (P<0.05) . Conclusion: Crotonaldehyde may induce inflammatory and oxidative stress damage in rats by up-regulating the expression of inflammatory factors in lung tissue and changing the oxidative balance.


Assuntos
Inflamação , Lesão Pulmonar/induzido quimicamente , Estresse Oxidativo , Aldeídos , Animais , Glutationa/análise , Pulmão , Masculino , Malondialdeído/análise , Peroxidase/análise , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/análise , Fator de Necrose Tumoral alfa/análise
8.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 737-745, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726503

RESUMO

Objective: To investigate the antioxidant mechanism of diallyl sulfide (DAS) in antagonizing the reduction in peripheral blood white blood cells (WBC) induced by benzene in rats. Methods: A total of 60 specific pathogen-free adult male Sprague-Dawley rats, with a body weight of 180-220 g, were selected, and after 5 days of adaptive feeding, they were randomly divided into blank control group, DAS control group, benzene model group, benzene+low-dose DAS group, benzene+middle-dose DAS group, and benzene+high-dose DAS group, with 10 rats in each group. The rats in the benzene+low-dose DAS group, the benzene+middle-dose DAS group, the benzene+high-dose DAS group, and the DAS control group were given DAS by gavage at a dose of 40, 80, 160, and 160 mg/kg·bw, respectively, and those in the blank control group and the benzene model group were given an equal volume of corn oil; 2 hours later, the rats in the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group were given a mixture of benzene (1.3 g/kg·bw) and corn oil (with a volume fraction of 50%), and those in the blank control group and the DAS control group were given an equal volume of corn oil. The above treatment was given once a day for 4 consecutive weeks. At 1 day before treatment, anticoagulated blood was collected from the jugular vein for peripheral blood cell counting. After anesthesia with intraperitoneally injected pentobarbital (50 mg/kg·bw), blood samples were collected from the abdominal aorta, serum was isolated, and the thymus, the spleen, and the femur were freed at a low temperature to measure oxidative and antioxidant indices. The femur at one side was freed for WBC counting in bone marrow. Results: Compared with the blank control group, the benzene model group had significant reductions in the volume, weight, and organ coefficient of the spleen and the thymus (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had significant increases in the volume of the spleen and the thymus and the weight and organ coefficient of the spleen (P<0.05), and the benzene+middle-dose DAS group and the benzene+high-dose DAS group had significant increases in the weight and organ coefficient of the thymus (P<0.05). Compared with the blank control group, the benzene model group had a significant reduction in WBC count in peripheral blood and bone marrow (P<0.05), and compared with the benzene model group, the benzene+middle-dose DAS group and the benzene+high-dose DAS group had a significant increase in WBC count in peripheral blood and bone marrow (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the serum level of malondialdehyde (MDA) (P<0.05) and significant reductions in total superoxide dismutase (T-SOD) activity, reduced glutathione (GSH) level, GSH/oxidized glutathione (GSSG) ratio, total antioxidant capacity (T-AOC) (P<0.05) ; compared with the benzene model group, the benzene+high-dose DAS group had a significant reduction in the serum level of MDA and significant increases in T-SOD activity, GSH level, GSH/GSSG ratio, and T-AOC (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA (P<0.05) and significant reductions in GSH level, GSH/GSSG ratio, and T-AOC (P<0.05) in the spleen; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in MDA level (P<0.05) and significant increases in GSH level and T-AOC (P<0.05), and the benzene+high-dose DAS group had significant increases in T-SOD activity and GSH/GSSG ratio (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA in bone marrow cells (BMCs) and peripheral blood mononucleated cells (PBMCs) (P<0.05) and a significant reduction in T-AOC in PBMCs (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in the level of MDA in BMCs and PBMCs (P<0.05), and the benzene+high-dose DAS group had significant increases in GSH level and GSH/GSSG ratio (P<0.05) . Conclusion: DAS can antagonize the benzene-induced reduction in peripheral blood WBC, possibly by exerting an anti-oxidative stress effect.


Assuntos
Compostos Alílicos/farmacologia , Antioxidantes/farmacologia , Leucopenia/tratamento farmacológico , Sulfetos/farmacologia , Animais , Benzeno/efeitos adversos , Glutationa/análise , Leucopenia/induzido quimicamente , Masculino , Malondialdeído/análise , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/análise
9.
Sheng Li Xue Bao ; 71(5): 689-697, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31646322

RESUMO

The aim of the present study was to investigate the role of ferroptosis in acute lung injury (ALI) mouse model induced by oleic acid (OA). ALI was induced in the mice via the lateral tail vein injection of pure OA. The histopathological score of lung, lung wet-dry weight ratio and the protein content of bronchoalveolar lavage fluid (BALF) were used as the evaluation indexes of ALI. Iron concentration, glutathione (GSH) and malondialdehyde (MDA) contents in the lung tissues were measured using corresponding assay kits. The ultrastructure of pulmonary cells was observed by transmission electron microscope (TEM), and the expression level of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA was detected by quantitative polymerase chain reaction (q-PCR). Protein expression levels of glutathione peroxidase 4 (GPX4), ferritin and transferrin receptor 1 (TfR1) in lung tissues were determined by Western blot. The results showed that histopathological scores of lung tissues, lung wet-dry weight ratio and protein in BALF in the OA group were higher than those of the control group. In the OA group, the mitochondria of pulmonary cells were shrunken, and the mitochondrial membrane was ruptured. The expression level of PTGS2 mRNA in the OA group was seven folds over that in the control group. Iron overload, GSH depletion and accumulation of MDA were observed in the OA group. Compared with the control group, the protein expression levels of GPX4 and ferritin in lung tissue were down-regulated in the OA group. These results suggest that ferroptosis plays a potential role in the pathogenesis of ALI in our mouse model, which may provide new insights for development of new drugs for ALI.


Assuntos
Lesão Pulmonar Aguda/patologia , Apoptose , Ácido Oleico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/química , Ciclo-Oxigenase 2/metabolismo , Ferritinas/metabolismo , Glutationa/análise , Glutationa Peroxidase/metabolismo , Ferro/análise , Sobrecarga de Ferro/fisiopatologia , Pulmão/citologia , Pulmão/patologia , Malondialdeído/análise , Camundongos , Microscopia Eletrônica de Transmissão , Membranas Mitocondriais/ultraestrutura
10.
Undersea Hyperb Med ; 46(4): 509-519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509907

RESUMO

Nitric oxide (NO) may protect against gas bubble formation and risk of decompression sickness. We have previously shown that the crucial co-factor tetrahydrobiopterin (BH4) is oxidized in a dose-dependent manner when exposed to hyperoxia similar to diving conditions but with minor effects on the NO production by nitric oxide synthase. By manipulating the intracellular redox state, we further investigated the relationship between BH4 levels and production of NO in human endothelial cells (HUVECs). HUVECs were cultured with and without ascorbic acid (AA) and the glutathione (GSH) synthesis inhibitor buthionine sulfoximine, prior to hyperoxic exposure. The levels of biopterins and GSH were determined in cell lysates while the production of NO was determined in intact cells. Omitting AA resulted in a 91% decrease in BH4 levels (0.49 ± 0.08 to 0.04 ± 0.01 pmol/106 cells, p⟨0.001) at 20 kPa oxygen (O2), and 88% decrease (0.24 ± 0.03 to 0.03 ± 0.01 pmol/106 cells, p=0.01) after exposure to 60 kPa O2. The NO generation was decreased by 23% (74.5 ± 2.2 to 57.3 ± 5.6 pmol/min/mg protein, p⟨0.001) at 20 kPa O2, but no significant change was observed at 60 kPa O2. GSH depletion had no effects on the NO generation. No correlation was found between NO generation and the corresponding intracellular BH4 concentration (p=0.675, r=-0.055) or the BH4 to BH2 ratio (p=0.983, r=0.003), determined across 18 in vitro experiments. Decreased BH4 in HUVECs, due to hyperoxia or lack of ascorbic acid, does not imply corresponding decreases in NO generation.


Assuntos
Ácido Ascórbico/administração & dosagem , Biopterina/análogos & derivados , Células Endoteliais/metabolismo , Hiperóxia/metabolismo , Óxido Nítrico/biossíntese , Antimetabólitos , Biopterina/análise , Biopterina/metabolismo , Butionina Sulfoximina , Doença da Descompressão/etiologia , Doença da Descompressão/prevenção & controle , Endotélio Vascular , Glutationa/análise , Glutationa/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxido Nítrico Sintase/metabolismo , Oxirredução , Oxigênio , Pressão Parcial
11.
Anal Chim Acta ; 1082: 146-151, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472703

RESUMO

Glutathione (GSH) is an important antioxygen and free radical scavenger in the organism. Level of GSH in vivo is associated with many diseases and specific recognition for GSH is very important. Here, a pyrene chalcone derivative 1 1-(2-hydroxyphenyl)-3-(1-pyrenyl)-2-propen-1-one as specific probe for GSH was developed. The probe can give rise to rapid blue fluorescence enhancement for GSH based on Michael addition reaction in pure PBS solution with high sensitivity, fast response rate and high specificity. The compound also can be applied for GSH detection in HeLa cell. Simultaneously, the compound exhibits blue fluorescence emission enhancement in methanol-water (1:1, v/v) solution with fluorescence quantum yield being 0.45 due to the competition of water molecules for hydrogen bonds between hydroxyl and carbonyl and the formation of structurally regular rodlike crystals, which allows regulating fluorescence emission by different solvent condition.


Assuntos
Chalconas/química , Corantes Fluorescentes/química , Glutationa/análise , Pirenos/química , Chalconas/efeitos da radiação , Fluorescência , Corantes Fluorescentes/efeitos da radiação , Células HeLa , Humanos , Luz , Limite de Detecção , Modelos Químicos , Pirenos/efeitos da radiação , Espectrometria de Fluorescência/métodos
12.
Chem Commun (Camb) ; 55(77): 11543-11546, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31490483

RESUMO

In this work, a simulated enzyme inhibition-based strategy was transplanted from natural peroxidase-based sensing methods for colorimetric nanoperoxidase-based biothiol detection. This work might provide some new perspectives for the construction and biomimetic regulation of mimicked biological signalling systems based on nanoperoxidases.


Assuntos
Corantes Fluorescentes/química , Glutationa/análise , Mercúrio/química , Nanopartículas Metálicas/química , Peroxidases/química , Pontos Quânticos/química , Compostos de Sulfidrila/análise , Materiais Biomiméticos/química , Técnicas Biossensoriais/métodos , Carbono/química , Catálise , Colorimetria/métodos , Ouro/química , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Limite de Detecção , Oxirredução , Peroxidases/antagonistas & inibidores , Propriedades de Superfície
13.
Analyst ; 144(17): 5284-5291, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31372627

RESUMO

5,10,15,20-Tetrakis(4-carboxyl phenyl)porphyrin (Por) modified Co(OH)2 deposited on the surface of GO nanocomposites (Por/Co(OH)2/GO) were prepared and characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and XRD. For the first time, H2TCPP/Co(OH)2/GO is found to have enhanced peroxidase-like activity and catalyze the oxidation of the substrate 3,3,5,5-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2). Notably, the colorless TMB rapidly transformed into blue oxTMB in just 60 s, which was easily observed visually. The catalytic kinetics of H2TCPP/Co(OH)2/GO is in accord with the Michaelis-Menten equation. The catalytic mechanism of H2TCPP/Co(OH)2/GO nanocomposites is attributed to hydroxyl radicals (˙OH), due to decomposition of H2O2, which is verified by using terephthalic acid as a fluorescent probe. What's more, H2O2 can be detected in a wide linear detection range from 5 to 35 mM with a detection limit of 0.385 mM. Furthermore, based on the excellent peroxidase-like activity of H2TCPP/Co(OH)2/GO, a colorimetric sensor is established to sensitively detect glutathione (GSH) in a linear range from 10 to 300 µM with a low detection limit of 9.5 µM.


Assuntos
Cobalto/química , Grafite/química , Hidróxidos/química , Nanocompostos/química , Peroxidases/química , Porfirinas/química , Benzidinas/química , Materiais Biomiméticos , Técnicas Biossensoriais/métodos , Catálise , Glutationa/análise , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Cinética , Limite de Detecção , Oxirredução , Sensibilidade e Especificidade , Propriedades de Superfície
14.
Anal Chim Acta ; 1080: 127-137, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31409462

RESUMO

Glutathione is an essential intra- and extracellular antioxidant. The level of glutathione in the body is highly related to different disease states and is a useful indicator of disease risk and oxidative stress status. We have developed a sensitive, selective, and comprehensive LC-MS/MS method for the absolute quantification and 13C-tracer analysis of total glutathione using dithiothreitol for the reduction of glutathione disulfide. The limit of detection (LOD) was 0.01 µM, while the lower limit of quantification (LLOQ) was 0.78 µM, with the linear (R = 0.9997) range extending up to 100 µM. The intra-run and inter-run coefficients of variation of 2.49% and 2.04%, respectively, attest to high repeatability. Mean (±SD) recoveries of three different concentrations (low, medium, high) of GSH spiked into aliquots of HCT116 cells prior to cell extraction were 108.9% (±2.1), 100.8% (±8.3), and 99.9% (±7.1), respectively. Finally, using a 20 Da wide Q1 window in MRM mode, we were able to detect and relatively quantify all isotopic labeling states of GSH extracted from HCT116 cells fed with either 13C-labeled glucose or glutamine.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glutationa/análise , Espectrometria de Massas em Tandem/métodos , Isótopos de Carbono , Ditiotreitol/química , Glucose/química , Glucose/metabolismo , Glutamina/química , Glutamina/metabolismo , Glutationa/química , Células HCT116 , Humanos , Marcação por Isótopo , Limite de Detecção , Oxirredução
15.
Molecules ; 24(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461829

RESUMO

In this work, a novel 7-hydroxybenzoxazinone-based fluorescent probe (PBD) for the selective sensing of biothiols is reported. Upon treatment with biothiols, PBD shows a strong fluorescence enhancement (up to 70-fold) and a large Stokes shift (155 nm). Meanwhile, this probe exhibits high resistance to interference from other amino acids and competing species. PBD features good linearity ranges with a low detection limit of 14.5 nM for glutathione (GSH), 17.5 nM for cysteine (Cys), and 80.0 nM for homocysteine (Hcy), respectively. Finally, the potential utility of this probe for biothiol sensing in living HeLa cells is demonstrated.


Assuntos
Benzoxazinas/química , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Cisteína/análise , Glutationa/análise , Células HeLa , Homocisteína/análise , Humanos , Limite de Detecção , Imagem Óptica
16.
ACS Appl Mater Interfaces ; 11(36): 32605-32612, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31423764

RESUMO

Drug-induced hepatotoxicity is the main cause of acute liver injury, and its early diagnosis is indispensable in pharmacological and pathological studies. As a hepatotoxicity indicator, the GSH distribution in the liver could reflect the damage degree in situ. In this work, we have provided a theoretical design strategy to determine the generation of photo-induced electron transfer mechanism and achieve high selectivity for the target. After that, we precisely synthesized a novel near-infrared fluorescent probe BSR1 to specifically monitor endogenous GSH and hepatotoxicity in biosystem with a moderate fluorescent quantum yield (Φ = 0.394) and low detection limit (83 nM) under this strategy. Moreover, this mapping method for imaging GSH depletion in vivo to assay hepatotoxicity may provide a powerful molecular tool for early diagnosis of some diseases and contribute to assay hepatotoxicity for the development of new drugs. Importantly, this theoretical calculation-guided design strategy may provide an effective way for the precise synthesis of the target-specific fluorescent probe and change this research area from "trial-and-error" to concrete molecular engineering.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Corantes Fluorescentes/síntese química , Glutationa/análise , Fígado/patologia , Modelos Teóricos , Animais , Linhagem Celular , Modelos Animais de Doenças , Corantes Fluorescentes/química , Humanos , Camundongos , Fenômenos Ópticos , Espectrometria de Fluorescência
17.
Adv Exp Med Biol ; 1155: 463-470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468423

RESUMO

We previously reported that taurine treatment inhibited arsenic (As)-induced apoptosis in the liver of mice. This study was designed to explore the effect of taurine on liver function and its underlying mechanism in As-exposed mice. Mice were randomly divided into 3 groups, ten mice in each group. Group 1, control group, only orally received drinking water alone. Group 2, As intoxication group, was exposed to 4 mg/L As2O3 via drinking water for 60 days. Group 3, taurine protection group, was treated with 4 mg/L As2O3 and 150 mg/kg both. Taurine administration significantly revered the increases of alanine transaminase (ALT) and aspartate transaminase (AST) activities in serum. The decrease of glutathione (GSH) was inhibited with taurine treatment in the liver of As-exposed mice. At the same time, taurine significantly inhihibited As-induced enhancement of malondialdehyde (MDA) in the liver. Here we show that taurine protective effect on liver function in As-exposed mice maybe involve lipid peroxidation.


Assuntos
Arsênico/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estresse Oxidativo , Taurina/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Suplementos Nutricionais , Glutationa/análise , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Malondialdeído/análise , Camundongos , Distribuição Aleatória
18.
Int J Mol Sci ; 20(13)2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31284671

RESUMO

(1) Antioxidants are involved in body protection mechanisms against reactive oxygen species. Amino acids such as glutathione (GSH) and N-acetylcysteine (NAC) are known to be involved in providing protection against oxidative lethality. A quick and simple method for the determination of NAC and GSH in various biological matrices such as urine, plasma, and homogenates of brain tissues has been developed and described in this work. (2) The assay is based on reversed phase high performance liquid chromatography with spectrofluorimetric detection and on-column derivatization. Butylamine and o-phthaldialdehyde have been used as derivatization reagents. Since o-phthaldialdehyde constitutes a part of the mobile phase, the derivatization reaction and chromatographic separation occur simultaneously. (3) Linearity in the detector response for NAC in human urine was observed in the range of 5-200 nmol mL-1, and NAC and GSH in the brain tissue homogenates were observed in the range of 0.5-5 nmol mL-1 and 0.5-15 nmol mL-1, respectively. Human plasma linearity ranges covered 0.25-5.00 nmol mL-1 and 0.5-15 nmol mL-1 for NAC and GSH, respectively. The LODs for NAC and GSH were 0.01 and 0.02 nmol mL-1 while the LOQs were 0.02 and 0.05 nmol mL-1, respectively. The usefulness of the proposed method was proven through its application to real samples.


Assuntos
Aminoácidos/sangue , Aminoácidos/urina , Antioxidantes/análise , Encéfalo/metabolismo , Butilaminas/química , Acetilcisteína/urina , Adulto , Animais , Calibragem , Dissulfetos/química , Glutationa/análise , Humanos , Indicadores e Reagentes , Limite de Detecção , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Suínos , o-Ftalaldeído/química
19.
Molecules ; 24(13)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277409

RESUMO

We report the development of a new colorimetric probe (L-ol) for investigations of the redox process regulated by hypochlorous acid (HOCl) and glutathione (GSH). The HOCl/GSH redox-switching cycle process was investigated in detail by UV-vis absorption spectroscopy, colorimetric analysis assay and high-resolution mass spectrometry (HRMS). The switchable absorbance responses were attributed to the HOCl-induced oxidation of the p-methoxyphenol unit to the benzoquinone derivative (L-one) and sequential reduction of L-one to hydroquinone (L-ol') by GSH. In phosphate-buffered saline (PBS) buffer, the absorbance of L-ol at 619 nm underwent a remarkable bathochromic-shift, accompanied by a color change from pale yellow to blue in the presence of HOCl. With further addition of GSH, the absorbance of L-one exclusively recovered to the original level. Meanwhile, the blue-colored solution returned to the naive pale yellow color in the presence of GSH. The detection limits for HOCl and GSH were calculated to be 6.3 and 96 nM according to the IUPAC criteria. Furthermore, L-ol-loaded chromatography plates have been prepared and successfully applied to visualize and quantitatively analyze HOCl in several natural waters.


Assuntos
Colorimetria/métodos , Glutationa/análise , Ácido Hipocloroso/análise , Benzoquinonas/química , Cor , Hidroquinonas/química , Sondas Moleculares/síntese química , Sondas Moleculares/química , Oxirredução , Espectrofotometria Ultravioleta , Fatores de Tempo , Água/química
20.
Chem Biol Interact ; 310: 108752, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31330126

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease whose pathogenesis is still not fully understood. Since inflammatory processes correlate with oxidative stress, the redox status may play a key role in AD. In this study, electron paramagnetic resonance (EPR) spectroscopy was mainly used to investigate the redox status in normal and inflammatory skin equivalents mimicking characteristics of AD in vitro using EPR spin probes (TEMPO, PCA) and a spin trap (DMPO). The total antioxidant status in the hydrophilic and lipophilic compartments of skin (microenvironment) showed no differences between the skin equivalents. In the inflammatory skin equivalents, a decreased glutathione concentration in the epidermis and an increased metabolic radical production could be observed compared to normal skin equivalents. The induction of external stress by simulated solar irradiation (UVB-NIR) resulted in the same amount and type of radicals in normal and inflammatory skin equivalents. For the first time, the antioxidant and oxidant status of inflammatory in vitro skin equivalents was analyzed by EPR to elucidate their redox status using different methods which focus on various microenvironments. Our investigations suggested that the redox status in atopic skin could be different, but this should be investigated more comprehensively, because the results can vary depending on the used methods and where the investigations take place.


Assuntos
Dermatite Atópica/patologia , Pele/patologia , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Glutationa/análise , Humanos , Inflamação/metabolismo , Oxirredução , Pele/metabolismo
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