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1.
Anal Chim Acta ; 1309: 342687, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772659

RESUMO

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.


Assuntos
Cisteína , Eletroforese em Gel de Poliacrilamida , Corantes Fluorescentes , Glutationa , Homocisteína , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Cisteína/análise , Cisteína/química , Glutationa/análise , Glutationa/química , Homocisteína/análise , Homocisteína/química , Animais , Fótons , Imagem Óptica , Arabidopsis/química , Humanos , Ciclização , Peixe-Zebra
2.
Reprod Domest Anim ; 59(5): e14596, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38757656

RESUMO

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.


Assuntos
Ácido Clorogênico , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , Mitocôndrias , Estresse Oxidativo , Partenogênese , Espécies Reativas de Oxigênio , Animais , Estresse Oxidativo/efeitos dos fármacos , Partenogênese/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Técnicas de Cultura Embrionária/veterinária , Ácido Clorogênico/farmacologia , Desenvolvimento Embrionário/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Blastocisto/efeitos dos fármacos , Suínos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Antioxidantes/farmacologia , Feminino , Glutationa/metabolismo
3.
Molecules ; 29(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38731608

RESUMO

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.


Assuntos
Colorimetria , Cobre , Glutationa , Peróxido de Hidrogênio , Nanoestruturas , Glutationa/análise , Glutationa/química , Colorimetria/métodos , Cobre/química , Nanoestruturas/química , Catálise , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Porosidade , Oxirredução , Ácidos Ftálicos/química , Humanos , Benzidinas/química , Limite de Detecção
4.
Biomed Khim ; 70(2): 73-82, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38711406

RESUMO

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.


Assuntos
Antioxidantes , Fungicidas Industriais , Glutationa , Ratos Wistar , Espécies Reativas de Oxigênio , Tiram , Animais , Masculino , Ratos , Glutationa/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fungicidas Industriais/toxicidade , Tiram/toxicidade , Antioxidantes/farmacologia , Boca/metabolismo , Boca/efeitos dos fármacos , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Glutationa Peroxidase/metabolismo
5.
J Agric Food Chem ; 72(19): 10897-10908, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691522

RESUMO

Gramine (GRM), which occurs in Gramineae plants, has been developed to be a biological insecticide. Exposure to GRM was reported to induce elevations of serum ALT and AST in rats, but the mechanisms of the observed hepatotoxicity have not been elucidated. The present study aimed to identify reactive metabolites that potentially participate in the toxicity. In rat liver microsomal incubations fortified with glutathione or N-acetylcysteine, one oxidative metabolite (M1), one glutathione conjugate (M2), and one N-acetylcysteine conjugate (M3) were detected after exposure to GRM. The corresponding conjugates were detected in the bile and urine of rats after GRM administration. CYP3A was the main enzyme mediating the metabolic activation of GRM. The detected GSH and NAC conjugates suggest that GRM was metabolized to a quinone imine intermediate. Both GRM and M1 showed significant toxicity to rat primary hepatocytes.


Assuntos
Ativação Metabólica , Citocromo P-450 CYP3A , Hepatócitos , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/genética , Microssomos Hepáticos/metabolismo , Glutationa/metabolismo , Inseticidas/toxicidade , Inseticidas/metabolismo , Alcaloides/metabolismo
6.
Sci Rep ; 14(1): 10835, 2024 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-38736022

RESUMO

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.


Assuntos
Encéfalo , Citarabina , Dopamina , Etoposídeo , Estresse Oxidativo , Ratos Wistar , Animais , Etoposídeo/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Citarabina/farmacologia , Dopamina/metabolismo , Ratos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Masculino , Peroxidação de Lipídeos/efeitos dos fármacos , Suplementos Nutricionais , Glutationa/metabolismo
7.
Sci Rep ; 14(1): 10905, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740939

RESUMO

Cancer-derived cell lines are useful tools for studying cellular metabolism and xenobiotic toxicity, but they are not suitable for modeling the biological effects of food contaminants or natural biomolecules on healthy colonic epithelial cells in a normal genetic context. The toxicological properties of such compounds may rely on their oxidative properties. Therefore, it appears to be necessary to develop a dual-cell model in a normal genetic context that allows to define the importance of oxidative stress in the observed toxicity. Given that the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered to be the master regulator of antioxidant defenses, our aim was to develop a cellular model comparing normal and Nrf2-depleted isogenic cells to qualify oxidative stress-related toxicity. We generated these cells by using the CRISPR/Cas9 technique. Whole-genome sequencing enabled us to confirm that our cell lines were free of cancer-related mutations. We used 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product closely related to oxidative stress, as a model molecule. Here we report significant differences between the two cell lines in glutathione levels, gene regulation, and cell viability after HNE treatment. The results support the ability of our dual-cell model to study the role of oxidative stress in xenobiotic toxicity.


Assuntos
Células Epiteliais , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Animais , Camundongos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Aldeídos/metabolismo , Glutationa/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular , Sistemas CRISPR-Cas , Peroxidação de Lipídeos/efeitos dos fármacos
8.
Neuroimage ; 293: 120632, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701994

RESUMO

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20-70 years) and 15 healthy participants (closed form, 7 females, age range 26-56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.


Assuntos
Envelhecimento , Glutationa , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Glutationa/metabolismo , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Adulto Jovem , Memória Espacial/fisiologia , Lobo Occipital/metabolismo , Giro do Cíngulo/metabolismo , Encéfalo/metabolismo
9.
Bull Exp Biol Med ; 176(5): 617-619, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38730108

RESUMO

We studied the effect of the HSP27 inhibitor, 5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)-isoxazole, at a final concentration of 0.1 µM and/or the apoptosis inducer dexamethasone at a final concentration of 10 µM on the content of hydroxyl radical, reduced and oxidized glutathione, HSP27, activity of glutathione reductase, glutathione peroxidase, caspase-3, and the number of Annexin+ Jurkat tumor cells. The involvement of HSP27 in apoptosis of Jurkat tumor cells was demonstrated. Simultaneous exposure to the HSP27 inhibitor and dexamethasone resulted in an increase in the level of HSP27 against the background of developing oxidative stress (increase in the concentration of hydroxyl radicals and changes in the state of the glutathione system).


Assuntos
Apoptose , Caspase 3 , Dexametasona , Glutationa , Proteínas de Choque Térmico HSP27 , Estresse Oxidativo , Humanos , Dexametasona/farmacologia , Células Jurkat , Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP27/genética , Glutationa/metabolismo , Caspase 3/metabolismo , Caspase 3/genética , Estresse Oxidativo/efeitos dos fármacos , Glutationa Redutase/metabolismo , Glutationa Peroxidase/metabolismo , Radical Hidroxila/metabolismo
10.
PLoS One ; 19(5): e0303040, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38713652

RESUMO

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.


Assuntos
Antioxidantes , Germinação , Glycine max , Melatonina , Valor Nutritivo , Resíduos de Praguicidas , Sementes , Melatonina/farmacologia , Germinação/efeitos dos fármacos , Resíduos de Praguicidas/análise , Sementes/efeitos dos fármacos , Sementes/química , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Glycine max/efeitos dos fármacos , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismo , Glycine max/química , Antioxidantes/metabolismo , Grão Comestível/efeitos dos fármacos , Grão Comestível/metabolismo , Fenóis/análise , Contaminação de Alimentos/análise , Glutationa/metabolismo
11.
BMC Plant Biol ; 24(1): 365, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706002

RESUMO

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.


Assuntos
Ácido Ascórbico , Glutationa , Glycine max , Plântula , Ácido gama-Aminobutírico , Ácido gama-Aminobutírico/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Plântula/fisiologia , Glycine max/efeitos dos fármacos , Glycine max/metabolismo , Glycine max/fisiologia , Ácido Ascórbico/metabolismo , Glutationa/metabolismo , Minerais/metabolismo , Tolerância ao Sal/efeitos dos fármacos , Estresse Salino/efeitos dos fármacos , Clorofila/metabolismo , Salinidade
12.
Nat Commun ; 15(1): 3684, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693181

RESUMO

The metal-nucleic acid nanocomposites, first termed metal-nucleic acid frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the synthesis efficiency and stability of MNFs by increasing oligonucleotide folding and entanglement probabilities during the reaction. Besides, longer oligonucleotides provide upgraded metal ions binding conditions, facilitating MNFs to load macromolecular protein drugs at room temperature. Furthermore, longer oligonucleotides facilitate functional expansion of nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, we build an interferon regulatory factor-1(IRF-1) loaded Ca2+/(aptamer-deoxyribozyme) MNF to target regulate glucose transporter (GLUT-1) expression in human epidermal growth factor receptor-2 (HER-2) positive gastric cancer cells. This MNF nanodevice disrupts GSH/ROS homeostasis, suppresses DNA repair, and augments ROS-mediated DNA damage therapy, with tumor inhibition rate up to 90%. Our work signifies a significant advancement towards an era of universal MNF application.


Assuntos
Aptâmeros de Nucleotídeos , DNA Catalítico , Neoplasias Gástricas , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Humanos , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Linhagem Celular Tumoral , DNA Catalítico/metabolismo , DNA Catalítico/química , Animais , Receptor ErbB-2/metabolismo , Fator Regulador 1 de Interferon/metabolismo , Fator Regulador 1 de Interferon/genética , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Reparo do DNA , Dano ao DNA , Glutationa/metabolismo , Glutationa/química , Ácidos Nucleicos/metabolismo , Ácidos Nucleicos/química
13.
Cir Cir ; 92(2): 165-173, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38782389

RESUMO

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.


Assuntos
Modelos Animais de Doenças , Passiflora , Ratos Wistar , Traumatismo por Reperfusão , Torção do Cordão Espermático , Animais , Masculino , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Passiflora/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Fitoterapia , Malondialdeído/análise , Malondialdeído/metabolismo , Testículo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Glutationa/metabolismo , Peroxidase/metabolismo , Peroxidase/análise , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Espermatogênese/efeitos dos fármacos
14.
ACS Sens ; 9(5): 2317-2324, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38752502

RESUMO

Cu2+ accelerates the viral-like propagation of α-synuclein fibrils and plays a key role in the pathogenesis of Parkinson's disease (PD). Therefore, the accurate detection of Cu2+ is essential for the diagnosis of PD and other neurological diseases. The Cu2+ detection process is impeded by substances that have similar electrochemical properties. In this study, graphdiyne (GDY), a new kind of carbon allotrope with strong electron-donating ability, was utilized for the highly selective detection of Cu2+ by taking advantage of its outstanding adsorption capacity for Cu2+. Density functional theory (DFT) calculations show that Cu atoms are adsorbed in the cavity of GDY, and the absorption energy between Cu and C atoms is higher than that of graphene (GR), indicating that the cavity of GDY is favorable for the adsorption of Cu atoms and electrochemical sensing. The GDY-based electrochemical sensor can effectively avoid the interference of amino acids, metal ions and neurotransmitters and has a high sensitivity of 9.77 µA·µM-1·cm-2, with a minimum detectable concentration of 200 nM. During the investigating pathogenesis and therapeutic process of PD with α-synuclein as the diagnostic standard, the concentration of Cu2+ in cells before and after L-DOPA and GSH treatments were examined, and it was found that Cu2+ exhibits high potential as a biomarker for PD. This study not only harnesses the favorable adsorption of the GDY and Cu2+ to improve the specificity of ion detection but also provide clues for deeper understanding of the role of Cu2+ in neurobiology and neurological diseases.


Assuntos
Cobre , Técnicas Eletroquímicas , Grafite , Doença de Parkinson , alfa-Sinucleína , Cobre/química , Doença de Parkinson/diagnóstico , Grafite/química , Humanos , Técnicas Eletroquímicas/métodos , alfa-Sinucleína/análise , alfa-Sinucleína/química , Teoria da Densidade Funcional , Levodopa/química , Limite de Detecção , Glutationa/química
15.
Int J Mol Sci ; 25(9)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38732088

RESUMO

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long term. Here, we analyzed the changes in plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timings of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that, throughout pregnancy until after delivery in patients, the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients. They could have clinical relevance for the prevention of complications related to AMA pregnancy.


Assuntos
Idade Materna , Células-Tronco Mesenquimais , Óxido Nítrico , Oxirredução , Espécies Reativas de Oxigênio , Substâncias Reativas com Ácido Tiobarbitúrico , Cordão Umbilical , Humanos , Feminino , Gravidez , Adulto , Células-Tronco Mesenquimais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Cordão Umbilical/citologia , Cordão Umbilical/metabolismo , Glutationa/metabolismo , Glutationa/sangue , Sobrevivência Celular , Estresse Oxidativo , Plasma/metabolismo
16.
Rev Int Androl ; 22(1): 29-37, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38735875

RESUMO

A significant clinical condition known as testicular torsion leads to permanent ischemic damage to the testicular tissue and consequent loss of function in the testicles. In this study, it was aimed to evaluate the protective effects of Astaxanthin (ASTX) on testicular damage in rats with testicular torsion/detorsion in the light of biochemical and histopathological data. Spraque Dawley rats of 21 were randomly divided into three groups; sham, testicular torsion/detorsion (TTD) and astaxanthin + testicular torsion/detorsion (ASTX + TTD). TTD and ASTX + TTD groups underwent testicular torsion for 2 hours and then detorsion for 4 hours. Rats in the ASTX + TTD group were given 1 mg/kg/day astaxanthin by oral gavage for 7 days before torsion. Following the detorsion process, oxidative stress parameters and histopathological changes in testicular tissue were evaluated. Malondialdehyde (MDA) and total oxidant status (TOS) levels were significantly decreased in the ASTX group compared to the TTD group, while superoxide dismutase (SOD), glutathione (GSH) and total antioxidant status (TAS) levels were increased (p < 0.05). Moreover, histopathological changes were significantly reduced in the group given ASTX (p < 0.0001). It was determined that ASTX administration increased Beclin-1 immunoreactivity in ischemic testicular tissue, while decreasing caspase-3 immunoreactivity (p < 0.0001). Our study is the first to investigate the antiautophagic and antiapoptotic properties of astaxanthin after testicular torsion/detorsion based on the close relationship of Beclin-1 and caspase-3 in ischemic tissues. Our results clearly demonstrate the protective effects of ASTX against ischemic damage in testicular tissue. In ischemic testicular tissue, ASTX contributes to the survival of cells by inducing autophagy and inhibiting the apoptosis.


Assuntos
Antioxidantes , Autofagia , Estresse Oxidativo , Ratos Sprague-Dawley , Torção do Cordão Espermático , Testículo , Xantofilas , Masculino , Animais , Xantofilas/farmacologia , Xantofilas/administração & dosagem , Autofagia/efeitos dos fármacos , Ratos , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Apoptose/efeitos dos fármacos , Malondialdeído/metabolismo , Distribuição Aleatória , Traumatismo por Reperfusão/prevenção & controle , Superóxido Dismutase/metabolismo , Glutationa/metabolismo
17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 286-295, 2024 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38755725

RESUMO

Bladder cancer (BC) is one of the 3 common malignant tumors in the urinary system, with high incidence, easy metastasis, poor therapeutic efficacy, and poor prognosis, which seriously threatens the health of human. Tumor cells exhibit a strong demand for iron, and iron overload can induce ferroptosis, which is an iron dependent cell death caused by lipid peroxidation and cell membrane damage. Therefore, ferroptosis has strong anti-tumor potential. The molecular mechanisms of ferroptosis is associated with abnormalities in cellular phospholipid metabolism and iron metabolism, and dysregulation of antioxidant and non-antioxidant systems Xc-/glutathione (GSH)/glutathione peroxidase 4 (GPX4). Ferroptosis relevant molecules play important roles in the occurrence and development, metastasis, drug resistance, and immune response of BC, and are expected to become targets for the treatment of BC.


Assuntos
Ferroptose , Ferro , Peroxidação de Lipídeos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Ferro/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Glutationa/metabolismo , Antioxidantes/metabolismo , Fosfolipídeos/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética
18.
ACS Appl Mater Interfaces ; 16(20): 25788-25798, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38716694

RESUMO

Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has great potential in tumor treatment. However, the presence of antioxidant glutathione (GSH) and the heat shock proteins (HSPs) expression caused by high temperature can weaken the effects of PDT and PTT. Here, a multifunctional nanocomplex BT&GA@CL is constructed to realize enhanced synergistic PDT/PTT. Cinnamaldehyde liposomes (CLs) formed by cinnamaldehyde dimer self-assembly were loaded with in gambogic acid (GA) and an aggregation-induced emission molecule BT to obtain BT&GA@CL. As a drug carrier, CL can consume glutathione (GSH) and release drugs responsively. The released BT aggregates can simultaneously act as both a photothermal agent and photosensitizer to achieve PDT and PTT under 660 nm laser irradiation. Specifically, GA as an HSP90 inhibitor can attenuate PTT-induced HSP90 protein expression, thereby weakening the tolerance of tumor cells to high temperatures and enhancing PTT. Such a multifunctional nanocomplex simultaneously modulates the content of GSH and HSP90 in tumor cells, thus enhancing both PDT and PTT, ultimately achieving the goal of efficient combined tumor suppression.


Assuntos
Glutationa , Lipossomos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Xantonas , Lipossomos/química , Glutationa/metabolismo , Glutationa/química , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Xantonas/química , Xantonas/farmacologia , Animais , Camundongos , Terapia Fototérmica , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Neoplasias/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/química , Antineoplásicos/química , Antineoplásicos/farmacologia
19.
Cancer Immunol Immunother ; 73(7): 131, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748299

RESUMO

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.


Assuntos
Linfócitos T CD8-Positivos , Glutationa , Imunoterapia , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Glutationa/metabolismo , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Prognóstico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Feminino , Biomarcadores Tumorais/metabolismo , Masculino , gama-Glutamiltransferase/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia
20.
Nat Commun ; 15(1): 4114, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750057

RESUMO

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.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Endorribonucleases , Ferroptose , Glutationa , Proteínas Serina-Treonina Quinases , Ferroptose/genética , Endorribonucleases/metabolismo , Endorribonucleases/genética , Animais , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Camundongos , Glutationa/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Glutamato-Cisteína Ligase/metabolismo , Glutamato-Cisteína Ligase/genética , Resposta a Proteínas não Dobradas , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/genética , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Masculino , Camundongos Knockout
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