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1.
Toxicol Lett ; 317: 24-44, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31541690

RESUMO

Exposure of humans to xenobiotic mixtures is a continuous state during their everyday routine. However, the majority of toxicological studies assess the in vivo effects of individual substances rather than mixtures. Therefore, our main objective was to evaluate the impact of the 12- and 18-month exposure of rats to a mixture containing 13 pesticides, food, and life-style additives in three dosage levels (i.e. 0.0025 × NOAEL, 0.01 × NOAEL, and 0.05 × NOAEL), on redox biomarkers in blood and tissues. Our results indicate that the exposure to the mixture induces physiological adaptations by enhancing the blood antioxidant mechanism (i.e., increased glutathione, catalase and total antioxidant capacity and decreased protein carbonyls and TBARS) at 12 months of exposure. On the contrary, exposure to the 0.05 × NOAEL dose for 18 months induces significant perturbations in blood and tissue redox profile (i.e., increased carbonyls and TBARS). This study simulates a scenario of real-life risk exposure to mixtures of xenobiotics through a long-term low-dose administration regimen in rats. The results obtained could support, at least in part, the necessity of introducing testing of combined stimuli at reference doses and long term for the evaluation of the risk from exposure to chemicals.


Assuntos
Aditivos Alimentares/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Xenobióticos/toxicidade , Animais , Biomarcadores/sangue , Catalase/sangue , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Feminino , Glutationa/sangue , Masculino , Nível de Efeito Adverso não Observado , Oxirredução , Carbonilação Proteica/efeitos dos fármacos , Ratos Sprague-Dawley , Medição de Risco , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
2.
Transplant Proc ; 51(8): 2667-2670, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31477426

RESUMO

BACKGROUND: Elevated levels of plasma homocysteine could, through homocysteine oxidation, induce the overproduction of reactive oxygen species, leading to a reduction in glutathione-related antioxidants, and may impair graft functions in patients with renal transplants. The purpose of this study was to determine whether plasma homocysteine, glutathione, or its related antioxidants were related to graft functions in patients with renal transplants. PATIENTS AND METHODS: We recruited 66 patients (mean age 48.4 years) with renal transplants (mean transplant duration 8.3 years). Patients were divided into 2 groups, based on their estimated glomerular filtration rate (eGFR): the moderate graft function group (eGFR ≥ 60 mL/min/1.73 m2, n = 37) and low graft function group (eGFR < 60 mL/min/1.73 m2, n = 29). We then determined their fasting levels of the following: malondialdehyde (MDA), homocysteine, cysteine, pyridoxal 5'-phosphate (PLP), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSH ratio, glutathione peroxidase (GSH-Px) activity. RESULTS: We found in the low graft function group significantly higher levels of plasma homocysteine, cysteine, GSH, and GSH/GSSG ratios. But an intergroup difference was not found regarding levels of MDA, PLP, GSSG, and GSH-Px activity. After adjusting for potential confounders, the increased plasma homocysteine and GSH levels were independently associated with lower eGFR. No interaction existed between homocysteine and GSH levels in association with eGFR. CONCLUSION: Increased plasma homocysteine and GSH levels appeared to be independent indicators of decreased graft functions in patients with renal transplants.


Assuntos
Função Retardada do Enxerto/sangue , Taxa de Filtração Glomerular/fisiologia , Glutationa/sangue , Homocisteína/sangue , Transplante de Rim , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Indian J Med Res ; 149(4): 497-502, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31411173

RESUMO

Background & objectives: Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD), but biomarkers to assess oxidative stress in patients with MDD have yielded ambiguous results. Glutathionyl haemoglobin (GS-Hb) has been reported as a stable and potential biomarker for oxidative stress in various clinical conditions. The objective of the study was to evaluate GS-Hb as a potential biomarker of oxidative stress in patients with MDD through its quantification and to compare the levels of GS-Hb in age- and gender-matched healthy controls. Methods: The levels of GS-Hb were estimated using liquid chromatography coupled to electrospray ionization mass spectrometry in patients diagnosed with MDD and in a subset of patients after six weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Results: GS-Hb levels in drug-naïve patients with MDD (n=26) were significantly elevated compared to matched healthy controls (n=17). GS-Hb levels were not significantly different between MDD patients with and without co-morbid anxiety disorders. There were no significant differences in GS-Hb levels following six weeks of treatment with SSRIs compared to baseline. Interpretation & conclusions: Compared to controls, GS-Hb level in patients with MDD was significantly elevated, suggestive of increased oxidative stress associated with MDD. However, six weeks of antidepressant treatment was not sufficient to modify the alterations in antioxidant/oxidant system. Further studies need to be done with a large sample of MDD patients with a longer duration of antidepressant treatment.


Assuntos
Biomarcadores/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Glutationa/sangue , Adulto , Antidepressivos/administração & dosagem , Cromatografia Líquida , Transtorno Depressivo Maior/patologia , Feminino , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Inibidores de Captação de Serotonina/administração & dosagem , Espectrometria de Massas por Ionização por Electrospray
4.
Anal Bioanal Chem ; 411(25): 6687-6695, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407048

RESUMO

Fluorescence resonance energy transfer (FRET) is a kind of energy transfer mechanism depending on the distance between donor and acceptor, which exhibited potential application in biosensors. In this study, an efficient fluorescence "turn-on" strategy for the detection of glutathione (GSH) has been established based on FRET between nitrogen and sulfur dual-doped carbon dots (N,S-CDs) and gold nanoparticles (Au NPs). A novel N,S-CDs was synthesized by a one-pot hydrothermal treatment of 3-aminothiophenol, which possessed excellent fluorescence property with the maximum emission wavelength of 530 nm. Then, the as-prepared N,S-CDs served as energy donor to transfer energy to Au NPs via FRET process, resulting in fluorescence quenching of N,S-CDs. However, the fluorescence of N,S-CDs was recovered efficiently by adding GSH into the mixture solution of N,S-CDs and Au NPs. Therefore, the FRET assembly of N,S-CDs and Au NPs was used as a fluorescence probe for the "turn-on" sensing GSH with the linear range from 3.8 to 415.1 µM and the limit detection of 0.21 µM. This nanosensor platform was employed to monitor GSH in serum samples with satisfying results. Graphical abstract.


Assuntos
Carbono/química , Corantes Fluorescentes/química , Glutationa/sangue , Ouro/química , Nanoestruturas/química , Técnicas Biossensoriais/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Nitrogênio/química , Enxofre/química
5.
J Toxicol Sci ; 44(8): 559-563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31378767

RESUMO

Acetaminophen (Paracetamol, APAP) has been widely used for many decades as an analgesic and antipyretic agent but APAP overdose often causes acute adverse reactions, particularly liver damage. The metabolically oxidized form of APAP, N-acetyl-p-benzoquinone imine (NAPQI), is chemically reactive and binds covalently to proteins. Therefore, NAPQI is believed to be the key metabolite that causes hepatotoxicity, especially under conditions of glutathione depletion. Other APAP-induced adverse reactions, such as skin damage, are rare and remain poorly studied. Here, we report a case study of a male patient who presented with an acute swelling skin rash (without hepatotoxicity) caused by therapeutic doses of APAP. Plasma samples were collected at 17 hr after dosing (during the manifestation of symptoms) and at one month (after recovery) and were subjected to LC-MS analysis of NAPQI-adducts. A significant concentration of NAPQI-cysteine adduct (33 pmol/mL) was found together with low concentrations of NAPQI-N-acetylcysteine adduct (2.0 pmol/mL) and NAPQI-glutathione adduct (0.13 pmol/mL). However, the NAPQI-albumin adduct was below the detection limit (below 0.001% modification on albumin) despite a previous report of high concentrations of NAPQI-albumin adduct following acute liver injury. Therefore, the observed APAP-induced skin damage may have had a different cause from APAP-induced liver injury.


Assuntos
Acetaminofen/efeitos adversos , Acetilcisteína/sangue , Benzoquinonas/efeitos adversos , Benzoquinonas/sangue , Cisteína/sangue , Edema/induzido quimicamente , Exantema/induzido quimicamente , Glutationa/sangue , Iminas/efeitos adversos , Iminas/sangue , Dermatopatias/induzido quimicamente , Acetilcisteína/metabolismo , Doença Aguda , Adulto , Benzoquinonas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Cromatografia Líquida , Cisteína/metabolismo , Glutationa/metabolismo , Humanos , Iminas/metabolismo , Masculino , Ligação Proteica , Albumina Sérica/metabolismo , Espectrometria de Massas em Tandem
6.
Talanta ; 204: 402-408, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357312

RESUMO

A novel plasmon enhanced electrochemiluminescence (ECL) sensor was fabricated for the highly sensitive detection of glutathione (GSH). First, Au nanoparticles (AuNPs) were coated with silica dioxide to prevent the direct contact of AuNPs and luminophore Ru(bpy)32+; then Ru(bpy)32+-containing silica layer (RuDS) was allowed to grow onto the obtained Au@SiO2. Owing to the high luminescence efficiency of RuDS and the surface plasmon resonance of AuNPs, the nanocomposite Au@SiO2@RuDS exhibited large ECL signal. As free radical scavenger, GSH could react with tri-n-propylamine radical (i.e. TPA+•) and effectively suppress the excitation of Ru(bpy)32+, thus made the ECL signal significantly decrease. By using Nafion as immobilization reagent, the resulting Au@SiO2@RuDS/GCE sensor showed wide linear response ranges (1.0 fM-1.0 nM and 1.0 nM-1.0 µM) and low detection limit (0.5 fM, S/N=3) for GSH. In addition, it had excellent stability, repeatability and reproducibility. The sensor was applied to the detection of GSH in human serum samples and satisfactory results were achieved.


Assuntos
Glutationa/sangue , Nanocompostos/química , Complexos de Coordenação/química , Espectroscopia Dielétrica/métodos , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Dióxido de Silício/química , Ressonância de Plasmônio de Superfície/métodos
7.
Talanta ; 204: 833-839, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357372

RESUMO

The peroxidase-like activity of ficin is relatively low, which limits its application. It was found that thiol groups of ficin could inhibit its peroxidase-like activity. So, two procedures, i.e., direct blocking with N-ethylmaleimide (NEM), or using tris (2-carboxyethyl) phosphine hydrochloride (TCEP) to interrupt disulfide bonds then blocking thiol groups with NEM, were applied to block thiol groups of ficin, ficin-NEM (ficin-N) and ficin-TCEP-NEM (ficin-TN) were produced, respectively. The blocking of thiol groups accelerated the peroxidase activity dramatically. The peroxidase catalytic activity of ficin-N and ficin-TN toward the peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by H2O2 was about 2.5-fold and 5-fold increase compared with ficin, respectively, which accompanied a color change from colorless to blue and followed classic Michaelis-Menten model. The kinetic parameters indicated that higher affinity of ficin-N (Km = 0.31) and ficin-TN (Km = 0.39) to H2O2 compared with ficin (Km = 0.58), and ficin-TN had the highest Kcat which increased by 6.5 times and 4.5 times for TMB and H2O2, respectively. According to these findings, a colorimetric method with high sensitivity for the detection of biothiols was developed due to sulfhydryl compounds inhibited the peroxidase activity of ficin. Comparing with ficin and ficin-N, ficin-TN had the widest detection range (0.01-16 µM) and the lowest detection limit (3 nM). The practical applications of ficin-TN for biothiol determination in human serum samples have been demonstrated with satisfactory results. Ficin-N and ficin-TN are promising to apply to the bioanalysis.


Assuntos
Cisteína/sangue , Ficina/química , Glutationa/sangue , Homocisteína/sangue , Peroxidases/química , Benzidinas/química , Compostos Cromogênicos/química , Colorimetria/métodos , Etilmaleimida/química , Humanos , Peróxido de Hidrogênio/química , Indicadores e Reagentes/química , Cinética , Limite de Detecção , Fosfinas/química
8.
J Pharm Pharmacol ; 71(8): 1324-1338, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168820

RESUMO

OBJECTIVES: Cuminaldehyde self-emulsified nanoemulsion (CuA-SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. METHODS: Cuminaldehyde self-emulsified nanoemulsion was developed through the self-nanoemulsification method using Box-Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA-SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in-vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. KEY FINDINGS: Cuminaldehyde self-emulsified nanoemulsion with acceptable characteristics (mean DS-48.83 ± 1.06 nm; PDI-0.232 ± 0.140; ZP-29.92 ± 1.66 mV; EE-91.51 ± 0.44%; and drug-loading capacity (DL)-9.77 ± 0.75%) was formulated. In-vitro drug release of CuA-SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA-SEN to CCl4 -induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA-SEN reduced the levels of tumour necrosis factor-alpha and interleukin-6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. CONCLUSIONS: These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti-inflammation and antihepatotoxicity of the drug.


Assuntos
Benzaldeídos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Emulsões/farmacologia , Nanoestruturas/administração & dosagem , Animais , Benzaldeídos/sangue , Benzaldeídos/farmacocinética , Disponibilidade Biológica , Tetracloreto de Carbono/efeitos adversos , Catalase/sangue , /farmacocinética , Liberação Controlada de Fármacos/efeitos dos fármacos , Emulsões/farmacocinética , Glutationa/sangue , Masculino , Camundongos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 222: 117260, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31226617

RESUMO

In this work, sodium salicylate and ethylenediamine (EDA) are used as the precursors to synthesize green fluorescent carbon dots (CDs). The CDs have some attractive properties, including better oxidation resistance, good water solubility, and excellent stability in high ionic strength solutions in a pH range of 6.0-10.0. Compared to other metal ions, only Hg2+ can quench the fluorescence of CDs, and with the introduction of biothiols, the fluorescence of the CDs/Hg2+ system can be recovered. Therefore, a turn off/on fluorescent sensor is constructed using CDs as a fluorescent probe, and the sensor is applied to the detection of Hg2+ and biothiols (glutathione, homocysteine and cysteine). In addition, the fluorescent sensor exhibits excellent selectivity and sensitivity. The linear range of Hg2+ is 0.05-10 µM with the detection limit of 44 nM. Glutathione, homocysteine, and cysteine have a linear response in the range of 0.5-10 µM with the limit of detection of 80, 76, and 69 nM, respectively. Furthermore, the fluorescence method is successfully used to detect Hg2+ in actual water samples and biothiols in human plasma.


Assuntos
Cisteína/sangue , Glutationa/sangue , Homocisteína/sangue , Mercúrio/análise , Pontos Quânticos/química , Poluentes Químicos da Água/análise , Carbono/química , Corantes Fluorescentes/química , Humanos , Limite de Detecção , Pontos Quânticos/ultraestrutura , Espectrometria de Fluorescência/métodos
10.
BMC Complement Altern Med ; 19(1): 97, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060549

RESUMO

BACKGROUND: Endothelial dysfunction (ED) has been observed in individuals with metabolic syndrome (MetS) and contributes to the initiation and progression of atherosclerosis. The primary management of MetS involves lifestyle modifications and treatment of its individual components with drugs all of which have side effects. Thus, it would be of advantageous if natural products would be used as adjuncts or substitutes for conventional drugs. The aim of the present study was to evaluate the effect of standardized aqueous extract of fruits of Phyllanthus emblica (P. emblica) 250 mg and 500 mg twice daily on ED, oxidative stress, systemic inflammation and lipid profile in subjects with MetS. METHODS: In this randomised, double-blind, placebo-controlled clinical study endothelial function was measured by calculating reflection index (RI) using digital plethysmograph. Oxidative stress biomarkers used were nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA). Systemic inflammation was measured by determining high sensitivity C-reactive protein (hsCRP) and dyslipidemia by lipid profile. ANOVA, paired and unpaired t-test were used. P-value < 0.05 was considered statistically significant. RESULTS: Out of 65 screened subjects all 59 enrolled completed the study. P. emblica aqueous extract (PEE), 250 mg and 500 mg twice daily dosing, showed significant reduction in mean RI, measure of endothelial function, at 8 and 12 weeks (p <  0.001) compared to baseline and placebo. Significant mean % change was seen in oxidative stress biomarkers, NO (+ 41.89%, + 50.7%), GSH (+ 24.31%, + 53.22%) and MDA (- 21.02%, - 31.44%), and systemic inflammation biomarker, hsCRP (- 39.68%, - 53.77%) (p <  0.001) at 12 weeks with 250 mg and 500 mg twice daily dosage respectively. Significant mean % change was also seen at 12 weeks with TC (- 7.71%, - 11.11%), HDL-C (+ 7.33% + 22.16%, p <  0.05), LDL-C (- 11.39%, - 21.8%) and TG (- 9.81%, - 19.22%) respectively with 250 mg and 500 mg twice daily (p <  0.001). PEE 500 mg twice daily was significantly more efficacious than the 250 mg twice daily and placebo. No participant discontinued the study because of adverse events. CONCLUSIONS: P.emblica aqueous extract significantly improved endothelial function, oxidative stress, systemic inflammation and lipid profile at both dosages tested, but especially at 500 mg twice daily. Thus, this product may be used as an adjunct to conventional therapy (lifestyle modification and pharmacological intervention) in the management of metabolic syndrome. TRIAL REGISTRATION: This study was registered with Clinical Trials Registry - India (CTRI) with the registration number of CTRI/2017/09/009606 . The study was registered retrospectively on 4th September 2017.


Assuntos
Inflamação/tratamento farmacológico , Lipídeos/sangue , Síndrome Metabólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Phyllanthus emblica , Extratos Vegetais , Idoso , Método Duplo-Cego , Dislipidemias/metabolismo , Feminino , Frutas/química , Glutationa/sangue , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(2): 183-187, 2019 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-31060672

RESUMO

Objective To investigate the changes of serum melatonin(MLT)and glutathione(GSH)levels in patients with Parkinson's disease(PD)and explore their relationships with disease severity,cognitive dysfunction,and sleep disorders. Methods Totally 50 PD patients treated in our center from September 2017 to February 2018 were enrolled as the PD group,and 50 healthy controls matched with age and sex as the control group.The improved Hoehn and Yahr scale was used to assess the severity of PD.The Montreal Cognitive Assessment Scale was used to assess the cognitive function and Pittsburgh's Sleep Quality Index was used to detect the patient's sleep.The serum levels of MLT and GSH were detected by enzyme-linked immunosorbent assay and the results were compared. Results Serum MLT level in the PD group was significantly higher than that in the control group [(84.12±6.58)pg/ml vs.(46.29±9.73)pg/ml,P=0.000],and serum GSH level was significantly lower than that in the control group [(21.07±12.05)µmol/L vs.(77.73±39.90)µmol/L,P=0.000].There was a positive correlation between serum MLT level and H-Y grade(r=0.537,P=0.000),and there was a negative correlation between serum GSH level and H-Y grade(r=-0.596,P=0.000).Serum MLT was negatively correlated with GSH level in PD patients(r=-0.842,P=0.000).The MLT level in PD patients with sleep disorders was significantly higher than in those without sleep disorders [(85.79±6.45)pg/ml vs.(78.84±3.54)pg/ml,P=0.001];the level of GSH in PD patients with cognitive dysfunction was significant lower than in the non-cognitive dysfunction group [(17.47±10.67)µmol/L vs.(26.09±12.23)µmol/L,P=0.011]. Conclusions Serum MLT level increases and GSH level decreases in PD patients.Both MLT and GSH are correlated with PD severity,and there is a negative correlation between MLT and GSH.In addition,PD patients with sleep disorders have higher MLT level and those with cognitive impairment tend to have lower GSH level.


Assuntos
Glutationa/sangue , Melatonina/sangue , Estresse Oxidativo , Doença de Parkinson/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/complicações , Humanos , Doença de Parkinson/complicações , Transtornos do Sono-Vigília/complicações
12.
PLoS One ; 14(4): e0215815, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31039164

RESUMO

BACKGROUND: Glutathione is an endogenous antioxidant found in oxidized (GSSG) and reduced (GSH) forms. Glutathione depletion is indicative of oxidative stress and occurs in various pathological conditions and following extreme exercise activity. Raising blood glutathione concentration has potential to attenuate and prevent chronic disease and also to improve recovery from exercise. There are a number of challenges to achieving this through traditional dietary supplements, and thus there is a need to develop optimized delivery methods to improve blood glutathione status. This study evaluated the effect of a novel glutathione formulation on blood glutathione parameters in healthy individuals. METHODS: 15 (8 male) healthy individuals (25±5y old, 78.0±14.6kg) participated in a single-blinded randomized placebo-controlled crossover study, with a minimum one-week washout period between treatments. Participants were overnight fasted and administered 1mL of a non-liposomal nano-size glutathione solution (NLNG) containing 200mg of glutathione or 1mL of placebo lacking glutathione. The solution was held in the mouth for 90 seconds before the remainder was swallowed. Blood was collected at baseline, 5, 10, 30, 60 and 120 minutes post-treatment. Protein-bound plasma and erythrocyte lysate concentrations of GSH and GSSG were measured at all time points using previously validated procedures. Linear mixed effects models were used to compare differences between baseline and post-treatment glutathione concentrations between NLNG and placebo for each parameter. RESULTS: There was a significant main effect for treatment type, such that increases in GSH concentration in erythrocyte lysate were greater following NLNG than placebo (p = 0.001). Similar significant main effects for treatment were also found for total (protein bound + erythrocyte lysate) GSH (p = 0.015) and GSSG (p = 0.037) concentration, as well as total blood glutathione pool (GSH+GSSG, p = 0.006). DISCUSSION: NLNG increased multiple blood glutathione parameters compared to placebo. Future research should examine whether NLNG can attenuate oxidative stress.


Assuntos
Absorção Fisiológica , Glutationa/sangue , Boca/metabolismo , Nanopartículas/química , Tamanho da Partícula , Adulto , Glutationa/administração & dosagem , Humanos , Lipossomos , Masculino , Projetos Piloto
13.
Biomolecules ; 9(5)2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31058806

RESUMO

Wu Shan Shen Cha is the leaf of Malus asiatica Nakai., a special type of tea that is consumed in the same way as green tea. To study the effect of Wu Shan Shen Cha-derived flavonoids (WSSCF) on lesions in the stomach, a 15% hydrochloric acid-95% ethanol (volume ratio 4:6) solution was used to induce gastric injury in mice. The degree of gastric injury was assessed using tissue specimens, and the effects of WSSCF on the serum levels of antioxidant enzymes were investigated. The results showed that WSSCF could alleviate the damage of the gastric mucosa and gastric wall caused by the hydrochloric acid-ethanol solution, decrease the tissue and serum levels of malondialdehyde (MDA) in mice with gastric injury, and increase the serum levels of superoxide dismutase (SOD) and glutathione (GSH). The results of quantitative polymerase chain reaction (qPCR) showed that WSSCF could increase the mRNA expression of Mn-SOD, Cu/Zn-SOD, catalase (CAT), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) in tissue specimens from mice with gastric injury and decrease the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). At the same time, the results of the high concentration of WSSCF (WSSCFH) group were closer to those of the drug (ranitidine) treatment group. Wu Shan Shen Cha-derived flavonoids had a good antioxidant effect, so as to play a preventive role in alcoholic gastric injury.


Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Etanol/efeitos adversos , Flavonoides/farmacologia , Malus/química , Folhas de Planta/química , Estômago/lesões , Animais , Líquidos Corporais/efeitos dos fármacos , Catalase/genética , Catalase/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação Enzimológica da Expressão Gênica , Glutationa/sangue , Glutationa/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Malondialdeído/sangue , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Padrões de Referência , Estômago/efeitos dos fármacos , Estômago/patologia , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
14.
Medicina (Kaunas) ; 55(5)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31086097

RESUMO

Background and objectives: The pathophysiology of tethered cord syndrome (TCS) in children is not well elucidated. An inelastic filum terminale (FT) is the main factor underlying the stretching of the spinal cord in TCS. Our study aimed to investigate the expression of glutathione-S-transferase (GST) in children and fetal FT samples in order to understand the relationship between this enzyme expression and the development of TCS. Materials and Methods: FT samples were obtained from ten children with TCS (Group 1) and histological and immunohistochemical examinations were performed. For comparison, FT samples from fifteen normal human fetuses (Group 2) were also analyzed using the same techniques. Statistical comparison was made using a Chi-square test. Results: Positive GST-sigma expression was detected in eight (80%) of 10 samples in Group 1. The positive GST-sigma expression was less frequent in nine (60%) of 15 samples from Group 2. No statistically significant difference was detected between the two groups (p = 0.197). Conclusions: Decreased FT elasticity in TCS may be associated with increased GST expression in FT. More prospective studies are needed to clarify the mechanism of the GST-TCS relationship in children.


Assuntos
Glutationa/sangue , Defeitos do Tubo Neural/enzimologia , Cauda Equina , Distribuição de Qui-Quadrado , Pré-Escolar , Feminino , Glutationa/análise , Humanos , Lactente , Masculino , Defeitos do Tubo Neural/sangue , Estudos Prospectivos , Transferases/análise , Transferases/sangue
15.
Pak J Pharm Sci ; 32(2 (Supplementary)): 779-784, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103972

RESUMO

Prevalence of pulmonary tuberculosis (TB) in Pakistan is due to poor living conditions, malnutrition and low immunity. The present project was conducted to show the role of selenium complement to enhance the immune status against TB. Total of 80 human TB patients were divided into treatment (selenium and anti-tuberculosis drug) and control groups (anti-tuberculosis drug). Levels of selenium, immunoglobulin and leukocyte count were determined before and after treatment. Selenium showed significant increase in levels of immunoglobulin and leukocyte count in patients as compared to control group. The level of SOD, catalase, glutathione and total antioxidants were remarkably lowered among control type group as compared to treatment type group (P<0.01). However, the values of lipid peroxidation products malondialdehyde (MDA) were notably higher in control group than treatment group.


Assuntos
Antioxidantes/uso terapêutico , Antituberculosos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Selênio/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antioxidantes/metabolismo , Catalase/sangue , Suplementos Nutricionais , Feminino , Glutationa/sangue , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Contagem de Leucócitos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Selênio/sangue , Superóxido Dismutase/sangue , Resultado do Tratamento , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia
16.
Medicina (Kaunas) ; 55(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137620

RESUMO

Background: The optimal use of oxygen at greater than atmospheric pressures in any operational or therapeutic application (hyperbaric oxygen, HBO2) requires awareness of the fact that the beneficial effects of oxygen coexist with toxic effects depending on the pressure and duration of exposure. In this study, we aimed to investigate the effect of HBO2 therapy on oxidative stress and antioxidant status in commonly used protocol for acute HBO2 indications, such as carbon monoxide intoxication, central retinal artery occlusion, crush injury, gas gangrene, and to compare it with normobaric oxygen (NBO2) in healthy rats. Materials and Methods: Fifty-six male, young adult Wistar albino rats were randomly divided into seven groups and named as Group I through Group VII. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), and erythrocyte glutathione (GSH) levels in control group were compared to the levels in other groups. Results: The increases in MDA levels and the decrease in SOD activities were statistically significant in HBO2 groups at the end of the first 24 h when compared to the control group, and the significant decrease in erythrocyte GSH level was only at 2.4 atmospheres absolute. Conclusions: The present study showed that pressure and frequency of exposure are important factors to consider when investigating HBO2-induced oxidative stress and antioxidant response.


Assuntos
Oxigenação Hiperbárica/métodos , Estresse Oxidativo/fisiologia , Pressão , Análise de Variância , Animais , Antioxidantes/fisiologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Glutationa/análise , Glutationa/sangue , Malondialdeído/análise , Malondialdeído/sangue , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Superóxido Dismutase/análise , Superóxido Dismutase/sangue
17.
Environ Pollut ; 252(Pt A): 21-30, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146235

RESUMO

Concentrations of mercury (Hg) were examined in the blood of mute swans from rural breeding sites and urban wintering areas in southern parts of Poland, Europe. The birds were classified into three age groups: cygnets, juveniles and adults. To investigate the potential impact of Hg on birds, hematocrit (Ht), reduced glutathione (GSH) levels and morphometric measurements were taken. Using morphometric parameters, we stated that all mute swans sampled were in good condition. The mercury concentrations found were rather low and differed between birds from industrialized wintering areas and rural breeding areas (means 7 ng/mL and 2 ng/mL, respectively). We found no difference in Hg concentrations between the sexes, but concentrations varied significantly between age groups (cygnets 2 ng/mL, juveniles 7 ng/mL and adults 6 ng/mL). A similar trend was observed for hematocrit levels. GSH levels did not differ between any of the groups studied. We found no significant relationship between blood parameters (Ht, GSH) in relation to Hg concentrations. We conclude that the Hg concentrations in blood may be influenced by industrialization, season and age, but generally low concentration such as those found by us do not affect Ht and GSH levels.


Assuntos
Envelhecimento/sangue , Anseriformes/sangue , Mercúrio/sangue , Animais , Aves , Feminino , Glutationa/sangue , Masculino , Polônia , Estações do Ano
18.
Oxid Med Cell Longev ; 2019: 9417048, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31093318

RESUMO

Buprenorphine and methadone are two substances widely used in the substitution treatment of patients who are addicted to opioids. Although it is known that they partly act efficiently towards this direction, there is no evidence regarding their effects on the redox status of patients, a mechanism that could potentially improve their action. Therefore, the aim of the present investigation was to examine the impact of buprenorphine and methadone, which are administered as substitutes to heroin-dependent patients on specific redox biomarkers in the blood. From the results obtained, both the buprenorphine (n = 21) and the methadone (n = 21) groups exhibited oxidative stress and compromised antioxidant defence. This was evident by the decreased glutathione (GSH) concentration and catalase activity in erythrocytes and the increased concentrations of thiobarbituric acid reactive substances (TBARS) and protein carbonyls in the plasma, while there was no significant alteration of plasma total antioxidant capacity (TAC) compared to the healthy individuals (n = 29). Furthermore, methadone revealed more severe oxidant action compared to buprenorphine. Based on relevant studies, the tested substitutes mitigate the detrimental effects of heroin on patient redox status; still it appears that they need to be boosted. Therefore, concomitant antioxidant administration could potentially enhance their beneficial action, and most probably, buprenorphine that did not induce oxidative stress in such a severe mode as methadone, on the regulation of blood redox status.


Assuntos
Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Dependência de Heroína/sangue , Dependência de Heroína/tratamento farmacológico , Metadona/uso terapêutico , Estresse Oxidativo , Adulto , Antioxidantes/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Catalase/sangue , Feminino , Glutationa/sangue , Humanos , Masculino , Oxirredução , Carbonilação Proteica , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
19.
Biomarkers ; 24(5): 492-498, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31099265

RESUMO

Objective: The aim of the present work is to evaluate the toxicity of titanium dioxide nanoparticles (TiO2NPs) according to their doses and particle sizes. Materials and methods: The effect of five days oral administration of TiO2NPs (21 and 80 nm) with different doses (50, 250 and 500 mg/kg body weight) was assessed in mice via measurement of oxidative stress markers; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitric oxide (NO), liver function indices; aspartate and alanine aminotransferases (AST and ALT), chromosomal aberrations and liver histopathological pattern. Results: The results revealed drastic alterations in all the measured parameters and showed positive correlation with the gradual dose increment. In addition, the smaller particle size of TiO2NPS (21 nm) had more adverse effect in all the selected biochemical parameters, genetic aberrations and histological investigations. Conclusions: Toxicity of TiO2NPs increases in a dose-dependent manner and vice versa with particles size. The evaluated biomarkers are good indicators for TiO2NPs toxicity. More detailed studies are required before the recommendation of TiO2NPS as food additives.


Assuntos
Biomarcadores/sangue , Nanopartículas/toxicidade , Titânio/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Catalase/sangue , Aberrações Cromossômicas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glutationa/sangue , Fígado/metabolismo , Fígado/patologia , Malondialdeído/sangue , Camundongos , Nanopartículas/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Superóxido Dismutase/sangue , Titânio/metabolismo
20.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 76-83, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30942158

RESUMO

The aim of this study is an investigation the protective effects of vitamin C (Vit C), vitamin E (Vit E), ß-carotene, sodium selenate combination in indomethacin-induced gastric mucosal damage in rats. Rats were divided into 6 groups. Group I: Intact animals (control). Group II: Control animals receiving Vit C (100 mg/kg/day), Vit E (100 mg/kg/day), ß-carotene (15 mg/kg/day) and sodium selenate (0.2 mg/kg/day) for 3 days. Group III: Animals receiving 25 mg/kg indomethacin. Group IV: Animals receiving Vit C, Vit E, ß-carotene and sodium selenate (in same doses) for 3 days 2 h before the administration of indomethacin. Group V: Animals receiving ranitidine (150 mg/kg) for 3 days. Group VI: Animals receiving ranitidine for 3 days 2 h before to the administration of indomethacin (in same dose and time). The administration of indomethacin caused a decrease in the levels of glutathione, mucus, hexosamine and in the activities of glutathione-S-transferase, sodium-potassium ATPase, thromboplastic activity and an increase in the aspartate and alanine amino transferase, alkaline phosphatase, catalase, lactate dehydrogenase, myeloperoxidase activities and sialic acid, lipid peroxidation and protein carbonyl levels.  Stomach caspase-8 immun+ cell numbers showed a slight increase while caspase-9 immun+ cell numbers reduced in indomethacin given group compared to control animals. Our results findings suggest that the combination of Vit C, Vit E, ß-carotene, sodium selenate and ranitidine has a protective effect on indomethacin-induced gastric mucosal injury of rats.


Assuntos
Antioxidantes/farmacologia , Mucosa Gástrica/lesões , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Caspases/metabolismo , Catalase/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/enzimologia , Mucosa Gástrica/patologia , Glutationa/sangue , Glutationa Transferase/metabolismo , Hexosaminas/metabolismo , Indometacina , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mucinas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Peroxidase , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo
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