Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 62.696
Filter
1.
Food Res Int ; 188: 114433, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823827

ABSTRACT

Whey derived peptides have shown potential activity improving brain function in pathological condition. However, there is little information about their mechanism of action on glial cells, which have important immune functions in brain. Astrocytes and microglia are essential in inflammatory and oxidative defense that take place in neurodegenerative disease. In this work we evaluate antioxidant and anti-inflammatory potential bioactivity of whey peptide in glial cells. Peptides were formed during simulated gastrointestinal digestion (Infogest protocol), and low molecular weight (<5kDA) peptides (WPHf) attenuated reactive oxygen species (ROS) production induced by hydrogen peroxide stimulus in both cells in dose-dependent manner. WPHf induced an increase in the antioxidant glutathione (GSH) content and prevented GSH reduction induced by lipopolysaccharides (LPS) stimulus in astrocytes cells in a cell specific form. An increase in cytokine mRNA expression (TNFα and IL6) and nitric oxide secretion induced by LPS was attenuated by WPHf pre-treatment in both cells. The inflammatory pathway was dependent on NFκB activation. Bioactive peptide ranking analysis showed positive correlation with hydrophobicity and negative correlation with high molecular weights. The sequence identification revealed 19 peptides cross-referred with bioactive database. Whey peptides were rich in leucine, valine and tyrosine in the C-terminal region and lysine in the N-terminal region. The anti-inflammatory and antioxidant potential of whey peptides were assessed in glia cells and its mechanisms of action were related, such as modulation of antioxidant enzymes and anti-inflammatory pathways. Features of the peptide structure, such as molecular size, hydrophobicity and types of amino acids present in the terminal region are associated to bioactivity.


Subject(s)
Anti-Inflammatory Agents , Antioxidants , Neuroglia , Whey Proteins , Antioxidants/pharmacology , Anti-Inflammatory Agents/pharmacology , Whey Proteins/pharmacology , Whey Proteins/chemistry , Whey Proteins/metabolism , Neuroglia/drug effects , Neuroglia/metabolism , Animals , Reactive Oxygen Species/metabolism , Lipopolysaccharides/pharmacology , Glutathione/metabolism , Peptides/pharmacology , Nitric Oxide/metabolism , Astrocytes/drug effects , Astrocytes/metabolism
2.
Mikrochim Acta ; 191(7): 365, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38831060

ABSTRACT

Copper-cobalt bimetallic nitrogen-doped carbon-based nanoenzymatic materials (CuCo@NC) were synthesized using a one-step pyrolysis process. A three-channel colorimetric sensor array was constructed for the detection of seven antioxidants, including cysteine (Cys), uric acid (UA), tea polyphenols (TP), lysine (Lys), ascorbic acid (AA), glutathione (GSH), and dopamine (DA). CuCo@NC with peroxidase activity was used to catalyze the oxidation of TMB by H2O2 at three different ratios of metal sites. The ability of various antioxidants to reduce the oxidation products of TMB (ox TMB) varied, leading to distinct absorbance changes. Linear discriminant analysis (LDA) results showed that the sensor array was capable of detecting seven antioxidants in buffer and serum samples. It could successfully discriminate antioxidants with a minimum concentration of 10 nM. Thus, multifunctional sensor arrays based on CuCo@NC bimetallic nanoenzymes not only offer a promising strategy for identifying various antioxidants but also expand their applications in medical diagnostics and environmental analysis of food.


Subject(s)
Antioxidants , Carbon , Colorimetry , Copper , Nitrogen , Nitrogen/chemistry , Colorimetry/methods , Carbon/chemistry , Antioxidants/chemistry , Antioxidants/analysis , Copper/chemistry , Cobalt/chemistry , Hydrogen Peroxide/chemistry , Humans , Catalysis , Limit of Detection , Glutathione/chemistry , Glutathione/blood , Dopamine/blood , Dopamine/analysis , Dopamine/chemistry , Benzidines/chemistry , Polyphenols/chemistry , Polyphenols/analysis , Ascorbic Acid/chemistry , Ascorbic Acid/blood , Ascorbic Acid/analysis , Oxidation-Reduction , Uric Acid/blood , Uric Acid/chemistry , Uric Acid/analysis , Cysteine/chemistry , Cysteine/blood
3.
PeerJ ; 12: e17541, 2024.
Article in English | MEDLINE | ID: mdl-38832034

ABSTRACT

Introduction: Oxidative and antioxidant pathways play essential roles in the development of alcohol-induced brain injury. The Nrf2 pathway is an endogenous antioxidant response pathway, but there has been little research on the role of Nrf2 in alcohol-related diseases. Thus, we examined the effects of alcohol and an Nrf2 agonist (TBHQ) on astrocyte function, mRNA expression, and metabolite content to further explore the protective mechanisms of Nrf2 agonists in astrocytes following alcohol exposure. Methods: CTX TNA2 astrocytes were cultured with alcohol and TBHQ and then subjected to transcriptome sequencing, LC-MS/MS analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and malondialdehyde (MDA) and superoxide dismutase (SOD) activity assays. Results: Alcohol exposure significantly increased malondialdehyde (MDA) levels while decreasing superoxide dismutase (SOD) levels in astrocytes. Treatment with TBHQ effectively reversed these effects, demonstrating its protective role against oxidative stress induced by alcohol. Transcriptome sequencing and qRT-PCR analysis revealed that TBHQ specifically upregulates genes involved in glutathione metabolism, including a notable increase in the expression of the glutathione S-transferase A5 (GSTA5) gene, which was suppressed by alcohol exposure. Additionally, metabolomic analysis showed that TBHQ regulates key components of ether lipid metabolism in alcohol-exposed astrocytes, with significant reductions in the levels of lysophosphatidylcholine (18:0) (LysoPC (18:0)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, both of which are critical markers in the ether lipid metabolic pathway. Discussion: The findings underscore the role of TBHQ as an Nrf2 agonist in mitigating alcohol-induced oxidative damage in astrocytes by modulating glutathione metabolism and ether lipid metabolism. The regulation of GSTA5 gene expression emerges as a key mechanism through which Nrf2 agonists confer neuroprotection against oxidative stress and lipid oxidation. These insights pave the way for potential therapeutic strategies targeting the Nrf2 pathway to protect astrocytes from alcohol-induced damage.


Subject(s)
Astrocytes , Ethanol , Glutathione , NF-E2-Related Factor 2 , Oxidative Stress , Astrocytes/drug effects , Astrocytes/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Animals , Ethanol/pharmacology , Oxidative Stress/drug effects , Glutathione/metabolism , Hydroquinones/pharmacology , Signal Transduction/drug effects , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Malondialdehyde/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Cells, Cultured
4.
Int J Nanomedicine ; 19: 5045-5056, 2024.
Article in English | MEDLINE | ID: mdl-38832334

ABSTRACT

Background: Chemodynamic therapy (CDT) is a new treatment approach that is triggered by endogenous stimuli in specific intracellular conditions for generating hydroxyl radicals. However, the efficiency of CDT is severely limited by Fenton reaction agents and harsh reaction conditions. Methods: Bimetallic PtMn nanocubes were rationally designed and simply synthesized through a one-step high-temperature pyrolysis process by controlling both the nucleation process and the subsequent crystal growth stage. The polyethylene glycol was modified to enhance biocompatibility. Results: Benefiting from the alloying of Pt nanocubes with Mn doping, the structure of the electron cloud has changed, resulting in different degrees of the shift in electron binding energy, resulting in the increasing of Fenton reaction activity. The PtMn nanocubes could catalyze endogenous hydrogen peroxide to toxic hydroxyl radicals in mild acid. Meanwhile, the intrinsic glutathione (GSH) depletion activity of PtMn nanocubes consumed GSH with the assistance of Mn3+/Mn2+. Upon 808 nm laser irradiation, mild temperature due to the surface plasmon resonance effect of Pt metal can also enhance the Fenton reaction. Conclusion: PtMn nanocubes can not only destroy the antioxidant system via efficient reactive oxygen species generation and continuous GSH consumption but also propose the photothermal effect of noble metal for enhanced Fenton reaction activity.


Subject(s)
Glutathione , Manganese , Platinum , Reactive Oxygen Species , Animals , Platinum/chemistry , Platinum/pharmacology , Reactive Oxygen Species/metabolism , Glutathione/chemistry , Humans , Manganese/chemistry , Manganese/pharmacology , Photothermal Therapy/methods , Mice , Metal Nanoparticles/chemistry , Hydrogen Peroxide/chemistry , Cell Line, Tumor , Hydroxyl Radical/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Iron/chemistry
5.
PLoS One ; 19(5): e0303040, 2024.
Article in English | MEDLINE | ID: mdl-38713652

ABSTRACT

In the present study, we attempted to use melatonin combined with germination treatment to remove pesticide residues from contaminated grains. High levels of pesticide residues were detected in soybean seeds after soaking with chlorothalonil (10 mM) and malathion (1 mM) for 2 hours. Treatment with 50 µM melatonin for 5 days completely removed the pesticide residues, while in the control group, only 61-71% of pesticide residues were removed from soybean sprouts. Compared with the control, melatonin treatment for 7 days further increased the content of ascorbic acid (by 48-66%), total phenolics (by 52-68%), isoflavones (by 22-34%), the total antioxidant capacity (by 37-40%), and the accumulated levels of unsaturated fatty acids (C18:1, C18:2, and C18:3) (by 17-30%) in soybean sprouts. Moreover, melatonin treatment further increased the accumulation of ten components of phenols and isoflavones in soybean sprouts relative to those in the control. The ability of melatonin to accelerate the degradation of pesticide residues and promote the accumulation of antioxidant metabolites might be related to its ability to trigger the glutathione detoxification system in soybean sprouts. Melatonin promoted glutathione synthesis (by 49-139%) and elevated the activities of glutathione-S-transferase (by 24-78%) and glutathione reductase (by 38-61%). In summary, we report a new method in which combined treatment by melatonin and germination rapidly degrades pesticide residues in contaminated grains and improves the nutritional quality of food.


Subject(s)
Antioxidants , Germination , Glycine max , Melatonin , Nutritive Value , Pesticide Residues , Seeds , Melatonin/pharmacology , Germination/drug effects , Pesticide Residues/analysis , Seeds/drug effects , Seeds/chemistry , Seeds/metabolism , Seeds/growth & development , Glycine max/drug effects , Glycine max/growth & development , Glycine max/metabolism , Glycine max/chemistry , Antioxidants/metabolism , Edible Grain/drug effects , Edible Grain/metabolism , Phenols/analysis , Food Contamination/analysis , Glutathione/metabolism
6.
BMC Plant Biol ; 24(1): 365, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38706002

ABSTRACT

BACKGROUND: In plants, GABA plays a critical role in regulating salinity stress tolerance. However, the response of soybean seedlings (Glycine max L.) to exogenous gamma-aminobutyric acid (GABA) under saline stress conditions has not been fully elucidated. RESULTS: This study investigated the effects of exogenous GABA (2 mM) on plant biomass and the physiological mechanism through which soybean plants are affected by saline stress conditions (0, 40, and 80 mM of NaCl and Na2SO4 at a 1:1 molar ratio). We noticed that increased salinity stress negatively impacted the growth and metabolism of soybean seedlings, compared to control. The root-stem-leaf biomass (27- and 33%, 20- and 58%, and 25- and 59% under 40- and 80 mM stress, respectively]) and the concentration of chlorophyll a and chlorophyll b significantly decreased. Moreover, the carotenoid content increased significantly (by 35%) following treatment with 40 mM stress. The results exhibited significant increase in the concentration of hydrogen peroxide (H2O2), malondialdehyde (MDA), dehydroascorbic acid (DHA) oxidized glutathione (GSSG), Na+, and Cl- under 40- and 80 mM stress levels, respectively. However, the concentration of mineral nutrients, soluble proteins, and soluble sugars reduced significantly under both salinity stress levels. In contrast, the proline and glycine betaine concentrations increased compared with those in the control group. Moreover, the enzymatic activities of ascorbate peroxidase, monodehydroascorbate reductase, glutathione reductase, and glutathione peroxidase decreased significantly, while those of superoxide dismutase, catalase, peroxidase, and dehydroascorbate reductase increased following saline stress, indicating the overall sensitivity of the ascorbate-glutathione cycle (AsA-GSH). However, exogenous GABA decreased Na+, Cl-, H2O2, and MDA concentration but enhanced photosynthetic pigments, mineral nutrients (K+, K+/Na+ ratio, Zn2+, Fe2+, Mg2+, and Ca2+); osmolytes (proline, glycine betaine, soluble sugar, and soluble protein); enzymatic antioxidant activities; and AsA-GSH pools, thus reducing salinity-associated stress damage and resulting in improved growth and biomass. The positive impact of exogenously applied GABA on soybean plants could be attributed to its ability to improve their physiological stress response mechanisms and reduce harmful substances. CONCLUSION: Applying GABA to soybean plants could be an effective strategy for mitigating salinity stress. In the future, molecular studies may contribute to a better understanding of the mechanisms by which GABA regulates salt tolerance in soybeans.


Subject(s)
Ascorbic Acid , Glutathione , Glycine max , Seedlings , gamma-Aminobutyric Acid , gamma-Aminobutyric Acid/metabolism , Seedlings/drug effects , Seedlings/metabolism , Seedlings/physiology , Glycine max/drug effects , Glycine max/metabolism , Glycine max/physiology , Ascorbic Acid/metabolism , Glutathione/metabolism , Minerals/metabolism , Salt Tolerance/drug effects , Salt Stress/drug effects , Chlorophyll/metabolism , Salinity
7.
Langmuir ; 40(21): 11098-11105, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38739904

ABSTRACT

Disulfide bonding has attracted intense interest in the tumor intracellular microenvironment-activated drug delivery systems (DDSs) in the last decades. Although various molecular structures of redox-responsive disulfide-containing DDSs have been developed, no investigation was reported on the effect of aggregation structures. Here, the effect of aggregation structures on pH/GSH dual-triggered drug release was investigated with the simplest pH/GSH dual-triggered doxorubicin-based drug self-delivery system (DSDS), the disulfide/α-amide-bridged doxorubicin dimeric prodrug (DDOX), as a model. By fast precipitation or slow self-assembly, DDOX nanoparticles were obtained. With similar diameters, they exhibited different pH/GSH dual-triggered drug releases, demonstrating the effect of aggregation structures. The π-π stacking in different degrees was revealed by the UV-vis, fluorescence, and BET analysis of the DDOX nanoparticles. The effect of the π-π stacking between the dimeric prodrug and its activated products on drug release was also explored with the molecular simulation approach. The finding opens new ideas in the design of high-performance DDSs for future precise tumor treatment.


Subject(s)
Disulfides , Doxorubicin , Drug Liberation , Glutathione , Prodrugs , Prodrugs/chemistry , Prodrugs/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacology , Hydrogen-Ion Concentration , Disulfides/chemistry , Glutathione/chemistry , Amides/chemistry , Nanoparticles/chemistry , Dimerization , Drug Carriers/chemistry
8.
Biomed Khim ; 70(2): 73-82, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38711406

ABSTRACT

Thiram is a dithiocarbamate derivative, which is used as a fungicide for seed dressing and spraying during the vegetation period of plants, and also as an active vulcanization accelerator in the production of rubber-based rubber products. In this study the content of reactive oxygen species (ROS) and the state of the glutathione system have been investigated in the oral fluid and gum tissues of adult male Wistar rats treated with thiram for 28 days during its administration with food at a dose of 1/50 LD50. Thiram induced formation of ROS in the oral cavity; this was accompanied by an imbalance in the ratio of reduced and oxidized forms of glutathione due to a decrease in glutathione and an increase in its oxidized form as compared to the control. Thiram administration caused an increase in the activity of glutathione-dependent enzymes (glutathione peroxidase, glutathione transferase, and glutathione reductase). However, the time-course of enzyme activation in the gum tissues and oral fluid varied in dependence on the time of exposure to thiram. In the oral fluid of thiram-treated rats changes in the antioxidant glutathione system appeared earlier. The standard diet did not allow the glutathione pool to be fully restored to physiological levels after cessation of thiram intake. The use of exogenous antioxidants resviratrol and an Echinacea purpurea extract led to the restoration of redox homeostasis in the oral cavity.


Subject(s)
Antioxidants , Fungicides, Industrial , Glutathione , Rats, Wistar , Reactive Oxygen Species , Thiram , Animals , Male , Rats , Glutathione/metabolism , Reactive Oxygen Species/metabolism , Fungicides, Industrial/toxicity , Thiram/toxicity , Antioxidants/pharmacology , Mouth/metabolism , Mouth/drug effects , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Glutathione Peroxidase/metabolism
9.
Molecules ; 29(9)2024 May 03.
Article in English | MEDLINE | ID: mdl-38731608

ABSTRACT

In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1-20 µM and 20-300 µM with a detection limit of 0.1 µM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.


Subject(s)
Colorimetry , Copper , Glutathione , Hydrogen Peroxide , Nanostructures , Glutathione/analysis , Glutathione/chemistry , Colorimetry/methods , Copper/chemistry , Nanostructures/chemistry , Catalysis , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/analysis , Porosity , Oxidation-Reduction , Phthalic Acids/chemistry , Humans , Benzidines/chemistry , Limit of Detection
10.
Reprod Domest Anim ; 59(5): e14596, 2024 May.
Article in English | MEDLINE | ID: mdl-38757656

ABSTRACT

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.


Subject(s)
Chlorogenic Acid , Embryo Culture Techniques , Embryonic Development , Mitochondria , Oxidative Stress , Parthenogenesis , Reactive Oxygen Species , Animals , Oxidative Stress/drug effects , Parthenogenesis/drug effects , Mitochondria/drug effects , Embryo Culture Techniques/veterinary , Chlorogenic Acid/pharmacology , Embryonic Development/drug effects , Reactive Oxygen Species/metabolism , Blastocyst/drug effects , Swine , Membrane Potential, Mitochondrial/drug effects , Antioxidants/pharmacology , Female , Glutathione/metabolism
11.
Sci Rep ; 14(1): 10835, 2024 05 12.
Article in English | MEDLINE | ID: mdl-38736022

ABSTRACT

Research on the relationships between oligoelements (OE) and the development of cancer or its prevention is a field that is gaining increasing relevance. The aim was to evaluate OE and their interactions with oncology treatments (cytarabine or etoposide) to determine the effects of this combination on biogenic amines and oxidative stress biomarkers in the brain regions of young Wistar rats. Dopamine (DA), 5-Hydroxyindoleacetic acid (5-Hiaa), Glutathione (Gsh), Tiobarbituric acid reactive substances (TBARS) and Ca+2, Mg+2 ATPase enzyme activity were measured in brain regions tissues using spectrophometric and fluorometric methods previously validated. The combination of oligoelements and cytarabine increased dopamine in the striatum but decreased it in cerebellum/medulla-oblongata, whereas the combination of oligoelements and etoposide reduced lipid peroxidation. These results suggest that supplementation with oligoelements modifies the effects of cytarabine and etoposide by redox pathways, and may become promising therapeutic targets in patients with cancer.


Subject(s)
Brain , Cytarabine , Dopamine , Etoposide , Oxidative Stress , Rats, Wistar , Animals , Etoposide/pharmacology , Oxidative Stress/drug effects , Cytarabine/pharmacology , Dopamine/metabolism , Rats , Brain/metabolism , Brain/drug effects , Male , Lipid Peroxidation/drug effects , Dietary Supplements , Glutathione/metabolism
12.
J Nanobiotechnology ; 22(1): 253, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755600

ABSTRACT

Improving cancer therapy by targeting the adverse tumor microenvironment (TME) rather than the cancer cells presents a novel and potentially effective strategy. In this study, we introduced FexMoyS nanoparticles (NPs), which act as sequential bioreactors to manipulate the TME. FexMoyS NPs were synthesized using thermal decomposition and modified with polyethylene glycol (PEG). Their morphology, chemical composition, and photothermal properties were characterized. The capability to produce ROS and deplete GSH was evaluated. Effects on CRC cells, including cell viability, apoptosis, and glycolysis, were tested through various in vitro assays. In vivo efficacy was determined using CRC-bearing mouse models and patient-derived xenograft (PDX) models. The impact on the MAPK signaling pathway and tumor metabolism was also examined. The FexMoyS NPs showed efficient catalytic activity, leading to increased ROS production and GSH depletion, inducing ferroptosis, and suppressing glycolysis in CRC cells. In vivo, the NPs significantly inhibited tumor growth, particularly when combined with NIR light therapy, indicating a synergistic effect of photothermal therapy and chemodynamic therapy. Biosafety assessments revealed no significant toxicity in treated mice. RNA sequencing suggested that the NPs impact metabolism and potentially immune processes within CRC cells. FexMoyS NPs present a promising multifaceted approach for CRC treatment, effectively targeting tumor cells while maintaining biosafety. The nanoparticles exhibit potential for clinical translation, offering a new avenue for cancer therapy.


Subject(s)
Colorectal Neoplasms , Ferroptosis , Glycolysis , Polyethylene Glycols , Reactive Oxygen Species , Animals , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colorectal Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Humans , Mice , Polyethylene Glycols/chemistry , Ferroptosis/drug effects , Glycolysis/drug effects , Cell Line, Tumor , Tumor Microenvironment/drug effects , Nanoparticles/chemistry , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Mice, Nude , Apoptosis/drug effects , Cell Survival/drug effects , Female , Glutathione/metabolism
13.
Cancer Immunol Immunother ; 73(7): 131, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748299

ABSTRACT

PURPOSE: The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS: We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by  Multiplex immunohistochemistry (mIHC). RESULTS: Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS: Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.


Subject(s)
CD8-Positive T-Lymphocytes , Glutathione , Immunotherapy , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/immunology , Stomach Neoplasms/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Glutathione/metabolism , Immunotherapy/methods , Tumor Microenvironment/immunology , Prognosis , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Female , Biomarkers, Tumor/metabolism , Male , gamma-Glutamyltransferase/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology
14.
Nat Commun ; 15(1): 4114, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750057

ABSTRACT

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is evolutionarily conserved. Genetic deficiency and pharmacological inhibition of IRE1α have similar effects in inhibiting ferroptosis and reducing renal ischemia-reperfusion injury in mice. Our findings reveal a previously unidentified role of IRE1α to regulate ferroptosis and suggests inhibition of IRE1α as a promising therapeutic strategy to mitigate ferroptosis-associated pathological conditions.


Subject(s)
Amino Acid Transport System y+ , Endoribonucleases , Ferroptosis , Glutathione , Protein Serine-Threonine Kinases , Ferroptosis/genetics , Endoribonucleases/metabolism , Endoribonucleases/genetics , Animals , Humans , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Mice , Glutathione/metabolism , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Glutamate-Cysteine Ligase/metabolism , Glutamate-Cysteine Ligase/genetics , Unfolded Protein Response , Reperfusion Injury/metabolism , Reperfusion Injury/genetics , Cell Line, Tumor , Mice, Inbred C57BL , Male , Mice, Knockout
15.
Anal Chim Acta ; 1309: 342687, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38772659

ABSTRACT

BACKGROUND: Cysteine (Cys), glutathione (GSH), and homocysteine (Hcy), as three major biothiols are involved in a variety of physiological processes and play a crucial role in plant growth. Abnormal levels of Cys can cause plants to fail to grow properly. To date, although a very large number of fluorescent probes have been reported for the detection of biothiols, very few of them can be used for the selective discrimination of Cys from GSH and Hcy due to their structural similarity, and only a few of them can be used for plant imaging. RESULTS: Here, three fluorescent probes (o-/m-/p-TMA) based on TMN fluorophore and the ortho-/meta-/para-substituted maleimide recognition groups were constructed to investigate the selective response effect of Cys. Compared to the o-/m-TMA, p-TMA can selectively detect Cys over GSH and Hcy with a rapid response time (10 min) and a low detection limit (0.26 µM). The theoretical calculation confirmed that the intermediate p-TMA-Cys-int has shorter interatomic reaction distances (3.827 Å) compared to o-/m-TMA-Cys (5.533/5.287 Å), making it more suitable for further transcyclization reactions. Additionally, p-TMA has been employed for selective tracking of exogenous and endogenous Cys in Arabidopsis thaliana using both single-/two-photon fluorescence imaging. Furthermore, single cell walls produced obvious two-photon fluorescence signals, indicating that p-TMA can be used for high-concentration Cys analysis in single cells. Surprisingly, p-TMA can be used as a fluorescent dye for protein staining in SDS-PAGE with higher sensitivity (7.49 µg/mL) than classical Coomassie brilliant blue (14.11 µg/mL). SIGNIFICANCE: The outstanding properties of p-TMA make it a promising multifunctional molecular tool for the highly selective detection of Cys over GSH and Hcy in various complex environments, including water solutions, zebrafish, and plants. Additionally, it has the potential to be developed as a fluorescent dye for a simple and fast SDS-PAGE fluorescence staining method.


Subject(s)
Cysteine , Electrophoresis, Polyacrylamide Gel , Fluorescent Dyes , Glutathione , Homocysteine , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Cysteine/analysis , Cysteine/chemistry , Glutathione/analysis , Glutathione/chemistry , Homocysteine/analysis , Homocysteine/chemistry , Animals , Photons , Optical Imaging , Arabidopsis/chemistry , Humans , Cyclization , Zebrafish
16.
Cir Cir ; 92(2): 165-173, 2024.
Article in English | MEDLINE | ID: mdl-38782389

ABSTRACT

OBJECTIVE: The current study aimed to explore the potential protective effect of Passiflora Incarnata L., (PI) in treating IR injury after testicular torsion in rats. MATERIALS AND METHODS: This research investigated the impact of PI on IR damage in male Wistar albino rats. Animals were divided to three groups: group 1 (sham), group 2 (IR), and group 3 (IR+PI). RESULTS: The malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels did not significantly differ across the groups (p = 0.830, p = 0.153 and p=0.140, respectively). However, Group 3 demonstrated a superior total antioxidant status (TAS) value compared to Group 2 (p = 0.020). Concurrently, Group 3 presented a significantly diminished mean total oxidant status (TOS) relative to Group 2 (p = 0.009). Furthermore, Group 3 showed a markedly improved Johnsen score relative to Group 2 (p < 0.01). IR caused cell degeneration, apoptosis, and fibrosis in testicular tissues. PI treatment, however, mitigated these effects, preserved seminiferous tubule integrity and promoted regular spermatogenesis. Furthermore, it reduced expression of tumor necrosis factor-alpha (TNF-α), Bax, and Annexin V, signifying diminished inflammation and apoptosis, thereby supporting cell survival (p < 0.01, p < 0.01, p < 0.01, respectively). CONCLUSIONS: This study revealed that PI significantly reduces oxidative stress and testicular damage, potentially benefiting therapies for IR injuries.


OBJETIVO: Explorar el posible efecto protector de Passiflora incarnata L. (PI) en el tratamiento de la lesión por isquemia-reperfusión (IR) después de una torsión testicular en ratas. MÉTODO: Se estudió el impacto de Passiflora incarnata en el daño por IR en ratas Wistar albinas machos. Los animales se dividieron tres grupos: 1 (simulado), 2 (IR) y 3 (IR+PI). RESULTADOS: Los niveles de malondialdehyde (MDA), myeloperoxidase (MPO) y glutathione (GSH) no difirieron significativamente entre los grupos (p = 0.830, p = 0.153 y p = 0.140, respectivamente). Sin embargo, el grupo 3 tuvo un valor de estado antioxidante total (TAS) superior en comparación con el grupo 2 (p = 0.020). Al mismo tiempo, el grupo 3 presentó un estado oxidante total (TOS) medio significativamente disminuido en comparación con el grupo 2 (p = 0.009). El grupo 3 mostró una mejora notable en la puntuación de Johnsen en comparación con el grupo 2 (p < 0.01). La IR causó degeneración celular, apoptosis y fibrosis en los tejidos testiculares. El tratamiento con PI mitigó estos efectos, preservó la integridad de los túbulos seminíferos y promovió la espermatogénesis regular. Además, redujo la expresión de factor de necrosis tumoral alfa, Bax y anexina V, lo que significa una disminución de la inflamación y de la apoptosis, respaldando así la supervivencia celular (p < 0.01, p < 0.01 y p < 0.01, respectivamente). CONCLUSIONES: Este estudio reveló que PI reduce significativamente el estrés oxidativo y el daño testicular, beneficiando potencialmente las terapias para lesiones por IR.


Subject(s)
Disease Models, Animal , Passiflora , Rats, Wistar , Reperfusion Injury , Spermatic Cord Torsion , Animals , Male , Spermatic Cord Torsion/complications , Spermatic Cord Torsion/drug therapy , Reperfusion Injury/prevention & control , Rats , Passiflora/chemistry , Plant Extracts/therapeutic use , Plant Extracts/pharmacology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Apoptosis/drug effects , Phytotherapy , Malondialdehyde/analysis , Malondialdehyde/metabolism , Testis/drug effects , Oxidative Stress/drug effects , Glutathione/metabolism , Peroxidase/metabolism , Peroxidase/analysis , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Spermatogenesis/drug effects
17.
PLoS One ; 19(5): e0304290, 2024.
Article in English | MEDLINE | ID: mdl-38787841

ABSTRACT

The aim of the study was to assess the impact of solarium light therapy on selected biological and biochemical parameters of peripheral blood in recreational horses. The study involved 10 horses divided into two groups of young (aged 5 to 7 years) and old (aged 14 to 19 years) individuals. All animals participated in light therapy sessions every other day. Blood was sampled three times during the study: before the treatment, after five light sessions, and after ten light sessions. Morphological parameters, the activity of antioxidant enzymes, TAS values, and the levels of glutathione (GSH), vitamin D3, vitamin C, and malondialdehyde (MDA) were measured in the whole blood. Light therapy contributed to an increase in MCV, HDW, MCVr, CHr and MPV indices, and simultaneously a decrease in the basophil counts, MCHC, RDW and CHCMr indices in both groups of horses (p ≤ 0.05). At the same time reticulocytes fell in older whereas white blood cells and monocytes counts expanded in younger individuals. The treatment also increased the activity of glutathione reductase (GR) and glutathione peroxidase (GPx) in young but decreased the activity of mentioned enzymes in blood plasma of old horses. The total antioxidant status (TAS) of the blood plasma rose progressively, whereas GSH levels declined in all individuals. Moreover, vitamin D3 levels did not change, whereas vitamin C levels gradually decreased during the experiment. The therapy also helped to reduce levels of MDA in the blood plasma, especially of older horses (p ≤ 0.05). In turn, GPx and GR activities as well as MDA levels significantly declined, whereas GSH levels notably elevated in erythrocytes (p ≤ 0.05). Solarium light therapy appears to have a beneficial impact on the morphological parameters and antioxidant status of blood in recreational horses in the winter season. However, the observed results could in part be attributed to the natural physiological adaptation of each individual organism to the treatment.


Subject(s)
Antioxidants , Animals , Horses/blood , Antioxidants/metabolism , Glutathione/blood , Glutathione/metabolism , Phototherapy/methods , Malondialdehyde/blood , Ascorbic Acid/blood , Male , Female , Glutathione Reductase/blood , Glutathione Reductase/metabolism , Glutathione Peroxidase/blood , Glutathione Peroxidase/metabolism , Cholecalciferol/blood , Aging/blood
18.
J Ethnopharmacol ; 331: 118292, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38705428

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Tabebuia impetiginosa (Bignoniaceae) was traditionally used for memory enhancement and central nervous system (CNS) stimulation. AIM OF THE STUDY: This study aims to create a metabolic profile of the ethyl acetate fraction of T. impetiginosa (TEF) and investigate for the first time its neuroprotective potential on cyclophosphamide (CP)-induced chemobrain, validating its traditional use. MATERIALS AND METHODS: Metabolite profiling of TEF was performed using Liquid Chromatography coupled with Quadrupole Time of Flight-Mass/Mass Spectrometry (LC-qTOF-MS/MS). For the in vivo study, CP (200 mg/kg, i.p.) was administered to induce cognitive impairment in rats; TEF (30 mg/kg, p.o.) was administered throughout the 14 days of the experiment to assess its role in mitigating CP-induced neuronal deficits. Behavioral tests including locomotor, Y-maze, and passive avoidance tests were conducted. Additionally, biochemical markers such as reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and caspase-3 immunoexpression were assessed in the hippocampus area. RESULTS: Forty-four phytoconstituents were tentatively identified in TEF, mainly iridoids and organic acids. TEF showed significant memory enhancement as evidenced by the increase in step-through latency in the passive avoidance test by 1.5 folds and the increase in sequence alternation percentage (SAP) in the Y-maze test by 67.3%, as compared to CP-group. Moreover, it showed pronounced antioxidant and anti-inflammatory potentials evidenced by the significant elevation in reduced glutathione (GSH) levels by 80% and a pronounced decline in MDA and TNF-α levels by 24% and 45%, respectively relative to the CP group. TEF treatment restored normal hippocampal histological features and attenuated apoptotic caspase-3 expression by 70% compared to the CP group. CONCLUSIONS: TEF can act as a promising natural scaffold in managing the chemobrain induced by CP in cancer patients.


Subject(s)
Neuroprotective Agents , Plant Extracts , Plant Leaves , Tandem Mass Spectrometry , Animals , Neuroprotective Agents/pharmacology , Tandem Mass Spectrometry/methods , Male , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Leaves/chemistry , Rats , Chromatography, Liquid/methods , Hippocampus/drug effects , Hippocampus/metabolism , Phytochemicals/pharmacology , Phytochemicals/analysis , Rats, Wistar , Cyclophosphamide/toxicity , Maze Learning/drug effects , Behavior, Animal/drug effects , Glutathione/metabolism , Oxidative Stress/drug effects
19.
Plant Physiol Biochem ; 211: 108675, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705047

ABSTRACT

Controlling light qualities have been acknowledged as an effective method to enhance the efficiency of phytoremediation, as light has a significant impact on plant growth. This study examined the effects of light qualities on cadmium (Cd) tolerance in aquatic plant Egeria densa using a combination of biochemical and transcriptomic approaches. The study revealed that E. densa exhibits higher resistance to Cd toxicity under red light (R) compared to blue light (B), as evidenced by a significant decrease in photosynthetic inhibition and damage to organelle ultrastructure. After Cd exposure, there was a significantly reduced Cd accumulation and enhanced levels of both glutathione reductase (GR) activity and glutathione (GSH), along with an increase in jasmonic acid (JA) in R-grown E. densa compared to B. Transcriptional analysis revealed that R caused an up-regulation of Cd transporter genes such as ABCG (G-type ATP-binding cassette transporter), ABCC (C-type ATP-binding cassette transporter), and CAX2 (Cation/H+ exchanger 2), while down-regulated the expression of HIPP26 (Heavy metal-associated isoprenylated plant protein 26), resulting in reduced Cd uptake and enhanced Cd exportation and sequestration into vacuoles. Moreover, the expression of genes involved in phytochromes and JA synthesis was up-regulated in Cd treated E. densa under R. In summary, the results suggest that R could limit Cd accumulation and improve antioxidant defense to mitigate Cd toxicity in E. densa, which might be attributed to the enhanced JA and phytochromes. This study provides a foundation for using light control methods with aquatic macrophytes to remediate heavy metal contamination in aquatic systems.


Subject(s)
Antioxidants , Cadmium , Light , Cadmium/toxicity , Cadmium/metabolism , Antioxidants/metabolism , Hydrocharitaceae/metabolism , Hydrocharitaceae/drug effects , Hydrocharitaceae/radiation effects , Oxylipins/metabolism , Gene Expression Regulation, Plant/drug effects , Gene Expression Regulation, Plant/radiation effects , Cyclopentanes/metabolism , Photosynthesis/drug effects , Glutathione/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Red Light
20.
Nat Commun ; 15(1): 4244, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762605

ABSTRACT

Cysteine metabolism occurs across cellular compartments to support diverse biological functions and prevent the induction of ferroptosis. Though the disruption of cytosolic cysteine metabolism is implicated in this form of cell death, it is unknown whether the substantial cysteine metabolism resident within the mitochondria is similarly pertinent to ferroptosis. Here, we show that despite the rapid depletion of intracellular cysteine upon loss of extracellular cystine, cysteine-dependent synthesis of Fe-S clusters persists in the mitochondria of lung cancer cells. This promotes a retention of respiratory function and a maintenance of the mitochondrial redox state. Under these limiting conditions, we find that glutathione catabolism by CHAC1 supports the mitochondrial cysteine pool to sustain the function of the Fe-S proteins critical to oxidative metabolism. We find that disrupting Fe-S cluster synthesis under cysteine restriction protects against the induction of ferroptosis, suggesting that the preservation of mitochondrial function is antagonistic to survival under starved conditions. Overall, our findings implicate mitochondrial cysteine metabolism in the induction of ferroptosis and reveal a mechanism of mitochondrial resilience in response to nutrient stress.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cysteine , Ferroptosis , Glutathione , Lung Neoplasms , Mitochondria , Humans , Cysteine/metabolism , Mitochondria/metabolism , Glutathione/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Cell Line, Tumor , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Iron-Sulfur Proteins/metabolism , Oxidation-Reduction , Mice
SELECTION OF CITATIONS
SEARCH DETAIL
...