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1.
Amino Acids ; 54(1): 33-46, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993628

RESUMO

Sodium chlorate (NaClO3) is a common non-selective herbicide that is also used in paper and pulp mills and is produced as a by-product during drinking water disinfection by chlorine dioxide. Here, we report the effect of dietary antioxidant taurine on NaClO3-induced cytotoxicity in human red blood cells (RBC). RBC were treated with 5 mM NaClO3, either alone or in presence of 1, 2.5 and 5.0 mM taurine. Incubation of RBC with NaClO3 alone caused hemolysis, increased oxidation of lipids and proteins, methemogobin level and decreased total sulfhydryl and glutathione content. It lowered the activities of antioxidant enzymes thioredoxin reductase, glutathione peroxidase, catalase and glutathione reductase, while Cu-Zn superoxide dismutase activity was increased. The antioxidant capacity of RBC was impaired. This strongly suggests that NaClO3 causes the induction of oxidative stress condition in RBC. The specific activities of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and plasma membrane bound enzymes, were also greatly altered. However, prior treatment of RBC with taurine conferred significant protection against NaClO3-induced oxidative damage and also improved the antioxidant defence system of cells. These results were supported by electron microscopy images of RBC. Treatment with NaClO3 alone converted the normal biconcave discoidal RBC to acanthocytes and echinocytes but this transformation was greatly prevented in the presence of taurine. Thus, taurine mitigates the cytotoxicity of NaClO3 in human RBC and can function as an effective chemoprotectant.


Assuntos
Cloratos , Taurina , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Cloratos/metabolismo , Cloratos/farmacologia , Eritrócitos , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo , Taurina/metabolismo , Taurina/farmacologia
2.
Nanotechnology ; 33(23)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35193121

RESUMO

We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2µM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Clorofilídeos , Nanopartículas , Fotoquimioterapia , Porfirinas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Clorofilídeos/uso terapêutico , Células Endoteliais/patologia , Feminino , Glutationa , Humanos , Isoquinolinas , Nanopartículas/química , Fármacos Fotossensibilizantes , Porfirinas/química , Pirazóis , Pirimidinas
3.
Microb Cell Fact ; 21(1): 153, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933377

RESUMO

BACKGROUND: Glutathione is a valuable tri-peptide that is industrially produced by fermentation using the yeast Saccharomyces cerevisiae, and is widely used in the pharmaceutical, food, and cosmetic industries. It has been reported that addition of L-serine (L-Ser) is effective at increasing the intracellular glutathione content because L-Ser is the common precursor of L-cysteine (L-Cys) and glycine (Gly) which are substrates for glutathione biosynthesis. Therefore, we tried to enhance the L-Ser biosynthetic pathway in S. cerevisiae for improved glutathione production. RESULTS: The volumetric glutathione production of recombinant strains individually overexpressing SER2, SER1, SER3, and SER33 involved in L-Ser biosynthesis at 48 h cultivation was increased 1.3, 1.4, 1.9, and 1.9-fold, respectively, compared with that of the host GCI strain, which overexpresses genes involved in glutathione biosynthesis. We further examined simultaneous overexpression of SHM2 and/or CYS4 genes involved in Gly and L-Cys biosynthesis, respectively, using recombinant GCI strain overexpressing SER3 and SER33 as hosts. As a result, GCI overexpressing SER3, SHM2, and CYS4 showed the highest volumetric glutathione production (64.0 ± 4.9 mg/L) at 48 h cultivation, and this value is about 2.5-fold higher than that of the control strain. CONCLUSIONS: This study first revealed that engineering of L-Ser and Gly biosynthetic pathway are useful strategies for fermentative glutathione production by S. cerevisiase.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Vias Biossintéticas , Cisteína/metabolismo , Fermentação , Glutationa/metabolismo , Engenharia Metabólica , Fosfoglicerato Desidrogenase/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Serina
4.
Gen Physiol Biophys ; 41(4): 309-318, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35938964

RESUMO

Selenium enhances the cellular antioxidant capacity and alleviates oxidative stress. We investigated the transcriptional and enzymatic activities of selenium-dependent glutathione peroxidase 1 and thioredoxin reductase 1 (TrxR1), and levels of glutathione, hydrogen peroxide, lipid peroxides, and protein carbonyls in primary passage 5 (P5) and senescent passage 25 (P25) and 30 (P30) fibroblasts. Cells were incubated in either standard Dulbecco growth medium (CM1) containing normal plasma selenium levels (0.8 µmol/l), or in CM2, CM3, and CM4 containing 3 µmol/l (5 µmol/l for TrxR1) sodium selenite, L-hydroxyselenomethionine, or Se-methylselenocysteine, respectively. Gene transcripts and activities of both investigated enzymes as well as the levels of reduced glutathione were significantly increased in CM2-, CM3-, and CM4-incubated senescent P25 and P35 cells compared against those incubated in CM1. In congruence, although all oxidative stress parameters including oxidized glutathione were significantly lower in CM2-, CM3-, and CM4-incubated senescent cells compared against those incubated in CM1, such reductions were of significantly higher magnitude in CM3 and CM4 cells compared against those in CM2. In conclusion, organic L-hydroxyselenomethionine and Se-methylselenocysteine are equally more potent at alleviating oxidative stress in senescent cells than inorganic sodium selenite, and thus could be beneficial for use in elderly subjects and those with oxidative stress-associated disease.


Assuntos
Selênio , Idoso , Antioxidantes/metabolismo , Fibroblastos , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Estresse Oxidativo , Selênio/farmacologia , Selenito de Sódio/farmacologia , Tiorredoxina Redutase 1/metabolismo
5.
Oxid Med Cell Longev ; 2022: 7302883, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910842

RESUMO

The process of tumor growth and deterioration is accompanied by increased oxygen free radicals, high glutathione concentration, hypoxia, and poor drug targeting during treatment, limiting the treatment of tumors. Metal-organic framework (MOF) preparations are continuously being developed and applied in tumor therapy. In this paper, the design and application of reactive oxygen species (ROS) and redox drug-loaded MOF preparations are reviewed. Moreover, the research challenges and application prospects of MOFs in tumor therapy are also discussed.


Assuntos
Estruturas Metalorgânicas , Sistemas de Liberação de Medicamentos , Glutationa , Oxirredução , Microambiente Tumoral
6.
Genet Res (Camb) ; 2022: 1792977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919037

RESUMO

Background: Oxidative stress is an important cause of liver disease and atherosclerosis. Natural substances with antioxidant activity are good drugs for treating liver disease and atherosclerosis. Trichosanthes kirilowii Peel Polysaccharide (TKPP) can remove DPPH (2,2-Diphenyl-1-picrylhydrazyl) free radicals and hydroxyl free radicals in vitro, which shows antioxidant activity. Therefore, it is speculated that it can protect human hepatoma cell line (HepG2) and umbilical artery smooth muscle cell (HUASMC) against oxidative damage by hydrogen peroxide (H2O2). Methods: Oxidative damage cell models of HepG2 and HUASMC were induced by H2O2. HepG2 and HUASMC were divided into blank group, H2O2 injury group, TKPP treatment group, and glutathione (GSH) positive control group. Cell Counting Kit-8 (CCK-8) was used to detect cell viability. The level of total GSH and the amount of Nitric oxide (NO) secreted by cells were detected by specific kits. The gene and protein expressions of catalase (CAT) and superoxide dismutase (SOD) were detected by fluorescence quantitative PCR and Western Blot. Results: In these two kinds of cells, compared with the control group, the survival rate, total GSH level, and NO secretion, CAT and SOD gene and protein expressions were significantly decreased in the H2O2 damaged group. In the TKPP treatment group, the cell survival rate was significantly elevated with the increase of the polysaccharide concentration, and the total GSH level, NO secretion, CAT and SOD gene expression, and protein expression levels were also significantly increased. Conclusion: TKPP can improve the activities of HepG2 and HUASMC cells damaged by H2O2 and protect the cellular antioxidant system.


Assuntos
Aterosclerose , Trichosanthes , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glutationa/metabolismo , Glutationa/farmacologia , Humanos , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo , Polissacarídeos/farmacologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Trichosanthes/metabolismo
7.
Eur Rev Med Pharmacol Sci ; 26(14): 5225-5232, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35916821

RESUMO

OBJECTIVE: We aimed at determining the protective effects of Pycnogenol on ethanol-induced retinotoxicity in an experimental model. MATERIALS AND METHODS: 30 male Wistar albino rats were randomly divided into three groups: an untreated healthy control (HC group), a group in which only ethanol was daily administered for six weeks (EtOH group), and a group in which ethanol + 40 mg/kg Pycnogenol was daily administered orally for six weeks (PEtOH group). The same volume (0.5 ml) of distilled water as solvent was applied in the same manner to the rats in the HC and EtOH groups. With the rats in the PEtOH and EtOH groups, 32% ethanol at a dose of 5 g/kg was administered by oral gavage one hour after the application of pycnogenol or distilled water. At the end of the experimental period, tissue samples were obtained for biochemical examination of malondialdehyde (MDA) and total glutathione (tGSH) levels, and afterwards, the eyes were removed for histopathological examination. RESULTS: Histopathological evaluations in the EtOH group showed significant destruction of retinal tissue with marked edema, decomposition and degeneration in layers, polymorphonuclear cell infiltration, dilatation and congestion in blood vessels. However, it was observed that MDA values increased and tGSH values decreased in the EtOH group. In the PEtOH group, MDA values decreased and GSH values increased. Again, degenerative changes were considerably less in this group. CONCLUSIONS:   In the light of biochemical markers and histopathological evaluations, it was observed that ethanol exposure caused a significant degeneration in the retinal tissue. It was found that Pycnogenol administration significantly reduced the destructive effects seen histopathologically. Biochemical results also coincided with other findings. It was concluded that ethanol-induced rethytosis can be prevented to a large extent by Pycnogenol administration.


Assuntos
Estresse Oxidativo , Doenças Retinianas , Animais , Antioxidantes/farmacologia , Etanol/toxicidade , Flavonoides , Glutationa/metabolismo , Masculino , Extratos Vegetais , Ratos , Ratos Wistar , Retina/metabolismo , Água
8.
Sci Rep ; 12(1): 13504, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931740

RESUMO

The increasing widespread use of lithium, which is preferred as an energy source in batteries produced for electric vehicles and in many electronic vehicles such as computers and mobile phones, has made it an important environmental pollutant. In this study, the toxicity profile of lithium carbonate (Li2CO3) was investigated with the Allium test, which is a bio-indicator test. Dose-related toxic effects were investigated using Li2CO3 at doses of 25 mg/L, 50 mg/L, and 100 mg/L. The toxicity profile was determined by examining physiological, cytotoxic, genotoxic, biochemical and anatomical effects. Physiological effects of Li2CO3 were determined by root length, injury rate, germination percentage and weight gain while cytotoxic effects were determined by mitotic index (MI) ratio and genotoxic effects were determined by micronucleus (MN) and chromosomal aberrations (CAs). The effect of Li2CO3 on antioxidant and oxidant dynamics was determined by examining glutathione (GSH), malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels, and anatomical changes were investigated in the sections of root meristematic tissues. As a result, Li2CO3 exhibited a dose-dependent regression in germination-related parameters. This regression is directly related to the MI and 100 mg/L Li2CO3 reduced MI by 38% compared to the control group. MN and CAs were observed at high rates in the groups treated with Li2CO3. Fragments were found with the highest rate among CAs. Other damages were bridge, unequal distribution of chromatin, sticky chromosome, vagrant chromosome, irregular mitosis, reverse polarization and multipolar anaphase. The genotoxic effects were associated with Li2CO3-DNA interactions determined by molecular docking. The toxic effects of Li2CO3 are directly related to the deterioration of the antioxidant/oxidant balance in the cells. While MDA, an indicator of lipid peroxidation, increased by 59.1% in the group administered 100 mg/L Li2CO3, GSH, which has an important role in cell defense, decreased by 60.8%. Significant changes were also detected in the activities of SOD and CAT, two important enzymes in antioxidant defense, compared to the control. These toxic effects, which developed in the cells belonging to the lithium-treated groups, were also reflected in the tissue anatomy, and anatomical changes such as epidermis cell damage, cortex cell damage, flattened cell nucleus, thickening of the cortex cell wall and unclear vascular tissue were observed in the anatomical sections. The frequency of these changes also increased depending on the Li2CO3 dose. As a result, Li2CO3, which is one of the lithium compounds, and has become an important contaminant in the environment with increasing technological developments, caused a combined and versatile toxicity in Allium cepa L. meristematic cells, especially by causing deterioration in antioxidant/oxidant dynamics.


Assuntos
Antioxidantes , Carbonato de Lítio , Antioxidantes/farmacologia , Dano ao DNA , Glutationa/farmacologia , Carbonato de Lítio/toxicidade , Simulação de Acoplamento Molecular , Cebolas , Oxidantes/farmacologia , Raízes de Plantas , Superóxido Dismutase/farmacologia
9.
Anal Chim Acta ; 1221: 340100, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934346

RESUMO

Glutathione (GSH) plays important roles in various physiological processes, thus highly sensitive assay of GSH and timely warning of its variation at trace level in complex biological matrixes is of great significance. However, this is challenging due to the coexisting reductive biomolecules and dynamic change of GSH levels in responding to various stimuli which remain largely unexploited. Herein, we report a dual mode protocol for the assay of GSH based on nanoconjugate g-C3N4:Tb/MnO2 between MnO2 nanosheets and terbium-doped g-C3N4 (g-C3N4:Tb) nanosheets. MnO2 moiety effectively quenches the emission at 546 nm from Tb3+ in the nanoconjugate, which is restored under the reduction of MnO2 by GSH to ensure fluorescence turn-on assay of GSH. Meanwhile, the generated Mn2+ facilitates inductively coupled plasma mass spectrometry (ICP-MS) detection to endow indirect highly sensitive assay of GSH. Fluorescence mode derived a limit of detection (LOD) of 0.17 µmol L-1 within a linear range of 0.5-160 µmol L-1, while ICP-MS resulted in a superior LOD of 0.016 µmol L-1 within 0.05-160 µmol L-1. Both detection modes provide excellent selectivity to GSH. The dual mode platform was validated by GSH assay in cell lysates. It was further demonstrated by monitoring the variation of dynamic change of GSH level under CuSO4 or cisplatin induced GSH consumption.


Assuntos
Corantes Fluorescentes , Compostos de Manganês , Glutationa/análise , Limite de Detecção , Compostos de Manganês/química , Nanoconjugados , Óxidos/química
10.
Anal Chim Acta ; 1221: 340122, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934360

RESUMO

Given the ever-growing food safety issues, the establishment of efficient approaches for monitoring food freshness attracts increasing attention. Volatile basic nitrogens (VBNs), including biogenic amines and ammonia, serve as an important biomarker for monitoring food freshness. In this study, a novel VBNs-responsive tag using glutathione capped copper nanoclusters (GSH-CuNCs) aggregates was developed as a fluorescent probe for in situ and real-time visual monitoring of salmon freshness, and the prepared GSH-CuNCs aggregates were characterized and their sensitivity for detecting VBNs using biogenic amines and ammonium hydroxide as the model targets was evaluated. Based on their remarkable response in liquid status, the GSH-CuNCs aggregates-based tag as a gas indicator was then fabricated, which exhibited visible colour changes under UV light as a function of ammonia vapour concentrations. More importantly, through exploring the sensing mechanism of GSH-CuNCs aggregates in VBNs detection, the existence of ligand exchange between the GSH-CuNCs and VBNs was observed and verified for the first time, confirming the effect of hydrogen bonding reported in the literature. Moreover, the GSH-CuNCs aggregates-based tag was applied for quantitative analysis of salmon freshness during different storage periods, which was validated by the standard method for detection of total VBNs in salmon. In addition, a colour card was developed and its feasibility for application in monitoring salmon freshness was validated, which could be used for consumers to obtain the freshness level directly with the naked eye, demonstrating the feasibility of the fabricated tag for real-time and visual monitoring of salmon freshness, thus showing great potentials for its practical applications in the food industry.


Assuntos
Nitrogênio , Salmão , Amônia , Animais , Cobre , Glutationa
11.
Anal Chim Acta ; 1221: 340172, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934388

RESUMO

Glutathione (GSH) plays vital roles in a variety of biological processes, and the development of simple and effective GSH detection method is an important research topic. Herein, a multifunctional probe based on Ag&Mn:ZnInS quantum dots (QDs) was developed for bimodal imaging of GSH. MnO2, as an efficient fluorescence quencher, was in-situ grown on the surface of QDs, and then modified with hyaluronic acid (HA) to improve the stability and targeted recognition capability of the probe due to the binding between HA and CD44 receptors. After MnO2 was deconstructed by GSH, the fluorescence of the probe was recovered and the generated Mn2+ could serve as good magnetic resonance imaging (MRI) contrast agent. Moreover, the near-infrared emission probe was successfully employed in living cell and zebrafish imaging due to its low toxicity and high anti-biological interference performance. This strategy provides a simple dual-mode fluorescence/MRI imaging of GSH, which may have a broad application in biological detection.


Assuntos
Pontos Quânticos , Animais , Meios de Contraste , Fluorescência , Glutationa/metabolismo , Imageamento por Ressonância Magnética , Compostos de Manganês , Óxidos/metabolismo , Pontos Quânticos/toxicidade , Peixe-Zebra
12.
Anal Chim Acta ; 1221: 340083, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934393

RESUMO

A nanozyme with 2D/1D heterostructure has been fabricated by the in-situ growth of molybdenum disulfide nanosheets (MoS2 NSs) onto single-walled carbon nanotubes (SWCNTs). It was discovered that the so-obtained SWCNTs@MoS2 nanozyme could exhibit greatly improved peroxidase-like catalysis, due to that the formed 2D/1D interfacial coupling in the heterostructure might provide more active sites and exhibit enhanced charge transferring during the catalytic reactions, as confirmed by the X-ray photoelectron spectroscopy, photoluminescence, electrochemical impedance spectra and radical capturing experiments. Furthermore, the catalysis of the developed nanozyme could be selectively inhibited by glutathione (GSH) through the competitive consumption of hydroxyl radicals with enzyme substrate in the catalytic reaction system. A SWCNTs@MoS2 catalysis-based colorimetric strategy was further proposed for the quantitative analysis of GSH with the concentrations linearly ranging from 0.01 to 1000.0 µM. Besides, the feasibility of the developed colorimetric method was evaluated by monitoring GSH separately in the extractions from hela cells and human serum, promising the extensive applications for monitoring various biological species like GSH in the clinical laboratory. Importantly, such a fabrication route for nanozyme with 2D/1D heterostructure may pave the way towards the wide applications for designing various nanzymes with improved catalysis.


Assuntos
Molibdênio , Nanotubos de Carbono , Catálise , Colorimetria/métodos , Glutationa/análise , Células HeLa , Humanos , Molibdênio/química
13.
Anal Chim Acta ; 1221: 340106, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934396

RESUMO

Due to high recurrence and metastasis rates leading to high mortality of hepatocellular carcinoma (HCC), detection of HCC circulating tumor cells (HCC-CTCs), which are regarded as an HCC blood marker, holds great significance in HCC early diagnosis, metastasis evolution, and prognosis. However, current existing circulating tumor cell (CTC) detection methods require multiple steps, and have low accuracy due to extremely rare CTCs in peripheral blood (PB). Thus, a simple and sensitive HCC-CTCs detection method is urgently needed. Here, a glutathione (GSH) activatable bioprobe (LacCC) targeting HCC cells was first developed through coordinating copper ions (Cu2+) to lactose modified coumarin derivative (LacC). Owing to the carbohydrate-protein interaction between lactose group and asialoglycoprotein receptors (ASGPRs) overexpressed on the membrane of HCC cells, LacCC displays selectivity towards HCC cells. The fluorescence of LacCC recovers rapidly within 2 min upon demetallation by high concentration of GSH in HCC cells. In simulated PB samples, as low as 10 HepG2 cells were detected via CLSM after removing red blood cells (RBCs) and culturing with LacCC. By coupling with flow cytometry, LacCC can achieve quantitative detection of HCC cells with low detection limit (LOD) of 3 cells per sample. Thus, this bioprobe possessing ASGPRs targetability and fast GSH responsiveness shows ultrasensitive detectability towards HCC cells in PB, which may have the potential for simple yet highly sensitive HCC-CTCs detection.


Assuntos
Técnicas Biossensoriais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Receptor de Asialoglicoproteína/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Glutationa , Humanos , Lactose , Neoplasias Hepáticas/metabolismo , Células Neoplásicas Circulantes/patologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-35914863

RESUMO

The benefits of practicing physical activity, such as weight loss and control, are commonly associated with caloric restriction diets and may be improved by the ingestion of thermogenic and ergogenic supplements. However, there is a lack of safety data on commonly marketed nutritional supplements. Therefore, this investigation aims to evaluate a pre-workout supplement for mutagenicity using the Ames test, hepatocytoxicity in HepG2 and F C3H cells after 24 h, 48 h and 72 h, genotoxicity using the CBMN assay, determination of gluthatione activity and computational prediction of the three major isolated compounds present in the supplement. The mutagenicity test showed a mutagenic response in TA98 His+ revertants of 5 mg/plate in the presence of metabolic activation, cytotoxicity in TA98 of 5 mg/plate in the absence of metabolic conditions, and in TA102 of 0.5 mg/plate both in the presence and absence of metabolic activation. In our in vitro eukaryotic cell viability, WST-1, LDH and alkaline phosphatase assays, the supplement showed hepatocytotoxicity both dose-dependently and time-dependently. In the cytokinesis blocking micronuclei assay, the supplement induced micronuclei, nuclear buds, nucleoplasmatic, bridge formation, and a decreased in nuclear division. In addition, the supplement decreased intra and extracellular GSH. Computational analysis showed that the three isolated compounds most present in the supplement have the potential to cause hepatotoxicity. In the present investigation, the pre-workout supplement induced mutagenic, genotoxic, and cytotoxic responses and GSH decrease. Thus, considering food safety and public health sanitary vigilance, the consumption of this pre-workout supplement may harm the health of its consumers.


Assuntos
Mutagênicos , Toxicogenética , Linhagem Celular , Dano ao DNA , Glutationa , Fígado , Testes de Mutagenicidade , Mutagênicos/toxicidade
15.
Oxid Med Cell Longev ; 2022: 5361241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915609

RESUMO

Ferroptosis is a type of regulated cell death that displays a promising therapeutic pathway for drug-resistant tumor cells. However, some pancreatic cancer (PC) cells are less sensitive to erastin-induced ferroptosis, and normal pancreatic cells are susceptible to this newly discovered cell death. Therefore, there is an urgent need to find drugs to enhance the sensitivity of these PC cells to erastin while limiting side effects. Here, we found that the oxidized form of vitamin C-dehydroascorbic acid (DHA) can be transported into PC cells expressing high levels of GLUT1, resulting in ferroptosis. Moreover, pharmacological vitamin C combined with erastin can synergistically induce ferroptosis of PC cells involving glutathione (GSH) reduction and ferrous iron accumulation while inhibiting the cytotoxicity of normal cells. Mechanistically, as a direct system Xc- inhibitor, erastin can directly suppress the synthesis of GSH, and the recycling of vitamin C and DHA is performed through GSH consumption, which is denoted as the classical mode. Furthermore, oxidative stress induced by erastin and vitamin C could enhance the expression of HMOX1 via the AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway to increase the labile iron level, which is named the nonclassical mode. In vivo experiments showed that erastin and vitamin C can significantly slow tumor growth in PC xenografts. In summary, the combination of erastin and vitamin C exerts a synergistic effect of classical and nonclassical modes to induce ferroptosis in PC cells, which may provide a promising therapeutic strategy for PC.


Assuntos
Ferroptose , Neoplasias Pancreáticas , Proteínas Quinases Ativadas por AMP , Ácido Ascórbico/farmacologia , Fator de Transcrição de Proteínas de Ligação GA , Glutationa/metabolismo , Heme Oxigenase-1 , Humanos , Ferro/metabolismo , Fator 2 Relacionado a NF-E2 , Fator 1 Nuclear Respiratório , Neoplasias Pancreáticas/tratamento farmacológico , Piperazinas
16.
Biomater Adv ; 137: 212841, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35929270

RESUMO

To explore new alternatives to combat increasing risk of bacterial infection, in this work, a cationic antimicrobial peptide (HHC10) and glutathione (GSH) co-ligand protected ultra-small gold nanoclusters (Au NCs) was constructed by a simple one-pot method. The intrinsic luminescent property of GSH-protected Au NCs (AuxGSH) endowed enhanced aggregation-induced emissions (AIEs) of co-ligand-protected Au NCs (AuxGSH-HHC10), which exhibited a very strong orange luminescence. Based on the AIE effect, for one thing, AuxGSH could be applied to rapidly and selectively detect Gram-positive bacteria. For another, AuxGSH-HHC10 exhibited potential for multicolor imaging of both Gram-negative and Gram-positive bacteria. Besides, as-synthesized AuxGSH-HHC10 could act as potent nanoantibiotics against both Gram-negative and Gram-positive bacteria, which could not only avoid drug tolerance but also be effective toward drug-resistance bacteria. The antibacterial mechanism indicated that the synergetic effect of the generation of reactive oxygen species (ROS), binding with DNA, and broad-spectrum antibacterial activity of HHC10 led to the membrane damage, depolarization, and interference of biological function, thus enhancing the antibacterial effect. More importantly, such an Au NCs could realize excellent therapeutic outcomes for wound healing in vivo, and showed good biocompatibility and biosafety toward health tissues. The results will provide a great potential for the application of Au NCs for imaging-guided antibacterial platform.


Assuntos
Ouro , Nanopartículas Metálicas , Antibacterianos/farmacologia , Glutationa/química , Ouro/farmacologia , Bactérias Gram-Positivas , Ligantes , Nanopartículas Metálicas/uso terapêutico , Cicatrização
17.
Oxid Med Cell Longev ; 2022: 2710607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936216

RESUMO

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF-α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.


Assuntos
Hepatite , Quercetina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Doxorrubicina/toxicidade , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glutationa/metabolismo , Hepatite/metabolismo , Inflamação/patologia , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar , Rutina/farmacologia , Rutina/uso terapêutico
18.
Arch Ital Biol ; 160(1-2): 20-27, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913387

RESUMO

This study aims to evaluate the changes in brain tissue and blood-brain barrier due to oxidative stress during cadmium (Cd) poisoning by biochemical, histopathological, and immunohistochemical methods. 170-190 g weighing eight-week-old female Wistar albino rats were divided into two groups (control and experimental), with 7 animals in each group. Experimental group rats were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. Biochemical, histopathological and immunohistochemical examination was performed. It was seen that brain malondialdehyde (MDA) levels increased significantly, and glutathione (GSH) and catalase activity (CAT) levels decreased. In addition to degeneration in some pyramidal cells and glial cells, deformity, and picnosis in the nucleus, dilation of the meninges and cortex vessels, and inflammation around the blood vessels were observed. An increase was found in ionized calcium binding adaptor molecule 1 (IBA-1) expression in microglia cells and degenerative endothelial cells, and increased glial fibrillary acidic protein (GFAP) expression was observed in astrocytes and degenerate neurons. It has been shown that cadmium toxicity may cause microgliosis and astrogliogenesis by inducing cytokine production due to cell degeneration, vascularity, and inflammation in the brain cortex and by affecting microglia, astrocytes cells.


Assuntos
Cloreto de Cádmio , Intoxicação por Cádmio , Proteínas de Ligação ao Cálcio , Proteína Glial Fibrilar Ácida , Proteínas dos Microfilamentos , Animais , Encéfalo/patologia , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Intoxicação por Cádmio/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Glutationa/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Proteínas dos Microfilamentos/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar
19.
BMC Cardiovasc Disord ; 22(1): 350, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918636

RESUMO

BACKGROUND: Hyperglycaemia is known to result in oxidative stress tissue injury and dysfunction. Interestingly, studies have reported hepatic and renal oxidative stress injury during prediabetes; however, any injury to the myocardium during prediabetes has not been investigated. Hence this study aims to assess changes in the myocardial tissue in an HFHC diet-induced model of prediabetes. METHODS: Male Sprague Dawley rats were randomly grouped into non-prediabetes and prediabetes (n = 6 in each group) and consumed a standard rat chow or fed a high-fat-high-carbohydrate diet respectively for a 20-week prediabetes induction period. Post induction, prediabetes was confirmed using the ADA criteria. Aldose reductase, NADH oxidase 1, superoxide dismutase, glutathione peroxide, cardiac troponins were analysed in cardiac tissue homogenate using specific ELISA kits. Lipid peroxidation was estimated by determining the concentration of malondialdehyde in the heart tissue homogenate according to the previously described protocol. Myocardial tissue sections were stained with H&E stain and analysed using Leica microsystem. All data were expressed as means ± SEM. Statistical comparisons were performed with Graph Pad instat Software using the Student's two-sided t-test. Pearson correlation coefficient was calculated to assess the association. Value of p < 0.05 was considered statistically significant. RESULTS: The prediabetes group showed a markedly high oxidative stress as indicated by significantly increased NADH oxidase 1 and malondialdehyde while superoxide dismutase and glutathione peroxide were decreased compared to non-prediabetes group. There was no statistical difference between cardiac troponin I and T in the non-prediabetes and prediabetes groups. Cardiac troponins had a weak positive association with glycated haemoglobin. CONCLUSION: The findings of this study demonstrate that prediabetes is associated with myocardial injury through oxidative stress. Future studies are to investigate cardiac contractile function and include more cardiac biomarkers.


Assuntos
Infarto do Miocárdio , Estado Pré-Diabético , Animais , Dieta Hiperlipídica/efeitos adversos , Glutationa/efeitos adversos , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , Peróxidos/efeitos adversos , Peróxidos/metabolismo , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/etiologia , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Superóxido Dismutase/metabolismo , Troponina
20.
Nat Commun ; 13(1): 4007, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35817773

RESUMO

Metabolites in the tumor microenvironment are a critical factor for tumor progression. However, the lack of knowledge about the metabolic profile in the bone marrow (BM) microenvironment of multiple myeloma (MM) limits our understanding of MM progression. Here, we show that the glycine concentration in the BM microenvironment is elevated due to bone collagen degradation mediated by MM cell-secreted matrix metallopeptidase 13 (MMP13), while the elevated glycine level is linked to MM progression. MM cells utilize the channel protein solute carrier family 6 member 9 (SLC6A9) to absorb extrinsic glycine subsequently involved in the synthesis of glutathione (GSH) and purines. Inhibiting glycine utilization via SLC6A9 knockdown or the treatment with betaine suppresses MM cell proliferation and enhances the effects of bortezomib on MM cells. Together, we identify glycine as a key metabolic regulator of MM, unveil molecular mechanisms governing MM progression, and provide a promising therapeutic strategy for MM treatment.


Assuntos
Mieloma Múltiplo , Medula Óssea/patologia , Bortezomib/farmacologia , Glutationa/metabolismo , Glicina/metabolismo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Microambiente Tumoral
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