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1.
Sci Rep ; 14(1): 2752, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307943

RESUMO

The present work is aimed to assess the protective influence of zinc oxide resveratrol nanoparticles against oxidative stress-associated testicular dysfunction. The number of 50 male albino rats were randomly separated into five groups (n = 10): Group I, control: rats gavage distilled water orally; Group II, Levofloxacin: rats that administered Levofloxacin (LFX) softened in distilled water at a dosage of 40 mg/kg-1 BW orally every other day; Group III, Zn-RSV: rats administered with Zn-RSV (zinc oxide resveratrol in distilled water at a dose 20 mg/kg-1 BW orally every other day; Group IV, (LFX + Zn-RSV): rats that were administered with Levofloxacin along with Zn-RSV nPs; Group V, Levofloxacin + Zn: rats were administered with Levofloxacin and Zno at a dose of 20 mg/kg-1 BW orally every other day as mentioned before. This study lasted for 2 months. Sera were collected to assess luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone values. Testicular tissues were utilized to evaluate levels of superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA), and catalase (CAT). Semen samples were utilized to measure their quality (motility, concentration, and vitality). Histopathological and immune histochemical techniques investigated the morphological changes in the testis. Rats treated with Levofloxacin showed significantly lower levels of serum LH, testosterone, FSH, testicular enzymatic NO, catalase, SOD, BAX, and BCL-2 immune reactivity and sperm quality but significantly greater testicular malondialdehyde and caspase-3 immuno-reactivity Compared to both control and zinc oxide resveratrol treatment. Zinc oxide resveratrol nanoparticles ameliorated the harmful side effects of Levofloxacin. Improvements were more pronounced in the co-treatment (LFX + Zn-RSV) Zinc oxide resveratrol group than in the co-treatment (LFX + Zno) Zinc oxide group. Zinc oxide resveratrol nanoparticles could be a possible solution for levofloxacin oxidative stress-induced fertility problems.


Assuntos
Nanopartículas , Doenças Testiculares , Óxido de Zinco , Humanos , Ratos , Masculino , Animais , Resveratrol/farmacologia , Resveratrol/metabolismo , Óxido de Zinco/farmacologia , Catalase/metabolismo , Levofloxacino/farmacologia , Ratos Wistar , Sêmen , Testículo/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Testosterona , Hormônio Foliculoestimulante , Hormônio Luteinizante , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismo , Água/metabolismo
2.
J Toxicol Environ Health A ; 87(8): 357-370, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38305282

RESUMO

Sodium dodecylbenzene sulfonate (SDBS) is an important surfactant used as a cleaning agent and industrial additive to remove unwanted chemicals which have been detected in the aquatic environment. The aim of this study was to examine the toxicological potential of SDBS on the gills of adult male zebrafish (Danio rerio) exposed to this chemical. For the 96 hr acute exposure, fish were divided into three groups: control, 0.25 mg/L, and 0.5 mg/L of SDBS. After the experiment, morphophysiological analyses (gill histopathology and histochemistry), oxidative stress (determination of gill activities of superoxide dismutase (SOD) and catalase (CAT)), and hematological analyses (leukocyte differentiation) were conducted. Data demonstrated that SDBS at both tested concentrations altered the histopathological index and initiated circulatory disturbances, as well as adverse, progressive, and immunological changes in the gills. In the 0.5 mg/L group, SOD activity decreased significantly, but CAT activity was not altered. Prominent blood changes observed in this group were neutrophilia and lymphocytosis. The number of mucous and chloride cells increased significantly in both groups. Taken together, our findings demonstrated that exposure of D. rerio to SDBS, even for 96 hr, produced adverse morphological and hematological effects associated with a reduction in SOD activity. Our findings indicate that exposure of aquatic species to the anionic surfactant SDBS may lead to adverse consequences associated with oxidative stress. Therefore, this study highlights the risks that this substance may pose to aquatic ecosystems and emphasizes the need for further investigations and strict regulations on its disposal.


Assuntos
Derivados de Benzeno , Poluentes Químicos da Água , Peixe-Zebra , Animais , Masculino , Peixe-Zebra/metabolismo , Brânquias , Ecossistema , Poluentes Químicos da Água/metabolismo , Catalase/metabolismo , Catalase/farmacologia , Estresse Oxidativo , Tensoativos/metabolismo , Tensoativos/farmacologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Sódio/metabolismo , Sódio/farmacologia
3.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338758

RESUMO

Catalases (CATs) play crucial roles in scavenging H2O2 from reactive oxygen species, controlling the growth and development of plants. So far, genome-wide identification and characterization of CAT genes in oil palm have not been reported. In the present study, five EgCAT genes were obtained through a genome-wide identification approach. Phylogenetic analysis divided them into two subfamilies, with closer genes sharing similar structures. Gene structure and conserved motif analysis demonstrated the conserved nature of intron/exon organization and motifs among the EgCAT genes. Several cis-acting elements related to hormone, stress, and defense responses were identified in the promoter regions of EgCATs. Tissue-specific expression of EgCAT genes in five different tissues of oil palm was also revealed by heatmap analysis using the available transcriptome data. Stress-responsive expression analysis showed that five EgCAT genes were significantly expressed under cold, drought, and salinity stress conditions. Collectively, this study provided valuable information on the oil palm CAT gene family and the validated EgCAT genes can be used as potential candidates for improving abiotic stress tolerance in oil palm and other related crops.


Assuntos
Arecaceae , Peróxido de Hidrogênio , Catalase/metabolismo , Filogenia , Peróxido de Hidrogênio/metabolismo , Transcriptoma , Arecaceae/genética , Arecaceae/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Óleo de Palmeira , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
PLoS One ; 19(2): e0289248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38335199

RESUMO

BACKGROUND: Agomelatine (AGO) is an antidepressant with unique pharmacological effects; however, its underlying mechanisms remain unknown. In this study, we examined agomelatine's effects on catalase activity, oxidative stress, and inflammation. METHODS: Chronic restraint stress (CRS) model mice were established over 4 weeks, and AGO 50 mg/kg was administered to different groups alongside a deferasirox (DFX) 10 mg/kg gavage treatment. Behavioral tests were performed to assess the effect of AGO on the remission of depression-like behaviors. Meanwhile, the expression of CAT, the oxidative stress signaling pathway and inflammatory protein markers were assessed using ELISA, qRT-PCR, Western blot, and immunohistochemistry. RESULTS: Four weeks of AGO treatment significantly improved depression-like behavior in mice through the activation of catalase in the hippocampus and serum of the model mice, increased superoxide dismutase expression, reduced malondialdehyde expression, and reduced oxidative stress damage. Deferasirox was found to offset this therapeutic effect partially. In addition, the inflammatory pathway (including nuclear factor-κB and nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) was not significantly altered. CONCLUSIONS: AGO can exert antidepressant effects by altering oxidative stress by modulating catalase activity.


Assuntos
Antioxidantes , Depressão , Camundongos , Animais , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/prevenção & controle , Catalase/metabolismo , Deferasirox/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico
5.
Nutrients ; 16(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38337652

RESUMO

Aging is a normal physiological process influenced by the combination of multiple mechanisms, primarily oxidative stress and neuroinflammation, which impact general physiology and brain function. Phenolic compounds have demonstrated the ability to slow down the aging process of the brain due to their antioxidant and anti-inflammatory effects. This study assessed the protective properties of catechin and polyphenon-60 in non-pathologically aged rats regarding visuo-spatial learning and the oxidative status of the frontal cortex. Old animals were treated with catechin or green tea extract (polyphenon-60) for 36 days, daily. Healthy old and young rats were used as controls. During the first training phase, treated rats executed the test better, locating the target in less time compared with the controls. Biomarkers of oxidative stress (catalase activities, superoxide dismutase, glutathione reductase, and glutathione S-transferase) were reduced in the brain of old animals, although their activities were partially improved after both antioxidant treatments. Furthermore, the rise in the production of reactive oxygen species and malondialdehyde levels-a marker of lipid peroxidation-in the frontal cortex of aged animals was significantly ameliorated after the interventions. In conclusion, old rats exhibited enhanced cognitive function and reduced stress levels following the administration of catechin and polyphenon-60.


Assuntos
Catequina , Disfunção Cognitiva , Polifenóis , Ratos , Animais , Catequina/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Peroxidação de Lipídeos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Catalase/metabolismo
6.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38396625

RESUMO

The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 µmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 µmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752-10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562-5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels.


Assuntos
Antioxidantes , Hiper-Homocisteinemia , Ratos , Masculino , Animais , Catalase/metabolismo , Antioxidantes/farmacologia , Ratos Wistar , Malato Desidrogenase/metabolismo , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/metabolismo , Solução Salina , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Homocisteína/metabolismo , Colo/metabolismo
7.
Cell Biochem Funct ; 42(2): e3935, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379260

RESUMO

50% of cases of infertility are caused by male factor, which acquired or congenital problems may bring on. Male infertility can be caused by oligospermia and asthenozoospermia, which are common. Since the same mutations that cause azoospermia in some people also cause oligozoospermia in others, oligozoospermia may be thought of as a less severe form of azoospermia. Studies have demonstrated telomere length, catalase activity, super oxide dismutase (SOD), and DNA fragmentation can be influential factors for male infertility. The amount of apoptosis, oxidative stress factors, telomere length, and DNA fragmentation were some aspects of healthy sperm that we chose to look into in this study and compare to oligospermia individuals. Oligospermia patients (n = 24) and fertile men (n = 27) semen samples were collected, and the apoptosis rate of sperms in both groups was analyzed (Flow cytometry). Also, gene expression of apoptotic and antiapoptotic markers and telomere length were examined (real-time polymerase chain reaction). The sperm DNA fragmentation kit was used to determine DNA fragmentation and to evaluate catalase and SOD activity; the specific kits and methods were utilized. Higher expression levels of caspase3 (p = .0042), caspase8 (p = .0145), caspase9 (p = .0275), and BAX (p = .0202) mRNA were observed in patients who had oligospermia. In contrast, lower mRNA expression of BCL-2 (p = .0009) was detected in this group. In addition, telomere length was decreased in the oligospermia group (p < .0001) compared to the health group. Moreover, the frequency of apoptosis is induced in patients (p = .0026). The catalase activity is low (p = .0008), but the SOD activity is high (p = .0015) in the patient group. As a result of our findings, we may list the sperm cell apoptosis rate, telomere length, the degree of sperm DNA fragmentation, and lastly, the measurement of significant and efficient oxidative stress markers like SOD and catalase in semen plasma among the principal diagnostic characteristics for oligospermia. Future studies will be better able to treat oligospermia by showing whether these indicators are rising or falling.


Assuntos
Azoospermia , Infertilidade Masculina , Oligospermia , Humanos , Masculino , Oligospermia/genética , Oligospermia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Catalase/genética , Catalase/metabolismo , Azoospermia/metabolismo , Sêmen/metabolismo , Espermatozoides/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/metabolismo , Antioxidantes/metabolismo , Fragmentação do DNA , Apoptose , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Telômero/metabolismo , RNA Mensageiro/metabolismo
8.
Cell Commun Signal ; 22(1): 142, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383392

RESUMO

BACKGROUND: Calcium is a ubiquitous intracellular messenger that regulates the expression of various genes involved in cell proliferation, differentiation, and motility. The involvement of calcium in diverse metabolic pathways has been suggested. However, the effect of calcium in peroxisomes, which are involved in fatty acid oxidation and scavenges the result reactive oxygen species (ROS), remains elusive. In addition, impaired peroxisomal ROS inhibit the mammalian target of rapamycin complex 1 (mTORC1) and promote autophagy. Under stress, autophagy serves as a protective mechanism to avoid cell death. In response to oxidative stress, lysosomal calcium mediates transcription factor EB (TFEB) activation. However, the impact of calcium on peroxisome function and the mechanisms governing cellular homeostasis to prevent diseases caused by calcium deficiency are currently unknown. METHODS: To investigate the significance of calcium in peroxisomes and their roles in preserving cellular homeostasis, we established an in-vitro scenario of calcium depletion. RESULTS: This study demonstrated that calcium deficiency reduces catalase activity, resulting in increased ROS accumulation in peroxisomes. This, in turn, inhibits mTORC1 and induces pexophagy through TFEB activation. However, treatment with the antioxidant N-acetyl-l-cysteine (NAC) and the autophagy inhibitor chloroquine impeded the nuclear translocation of TFEB and attenuated peroxisome degradation. CONCLUSIONS: Collectively, our study revealed that ROS-mediated TFEB activation triggers pexophagy during calcium deficiency, primarily because of attenuated catalase activity. We posit that calcium plays a significant role in the proper functioning of peroxisomes, critical for fatty-acid oxidation and ROS scavenging in maintaining cellular homeostasis. These findings have important implications for signaling mechanisms in various pathologies, including Zellweger's syndrome and ageing.


Assuntos
Cálcio , Macroautofagia , Espécies Reativas de Oxigênio/metabolismo , Cálcio/metabolismo , Catalase/metabolismo , Estresse Oxidativo , Autofagia/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo
9.
Microbiol Spectr ; 12(2): e0316923, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38206032

RESUMO

Yeast cells involved in fermentation processes face various stressors that disrupt redox homeostasis and cause cellular damage, making the study of oxidative stress mechanisms crucial. In this investigation, we isolated a resilient yeast strain, Candida nivariensis GXAS-CN, capable of thriving in the presence of high concentrations of H2O2. Transcriptomic analysis revealed the up-regulation of multiple antioxidant genes in response to oxidative stress. Deletion of the catalase gene Cncat significantly impacted H2O2-induced oxidative stress. Enzymatic analysis of recombinant CnCat highlighted its highly efficient catalase activity and its essential role in mitigating H2O2. Furthermore, over-expression of CnCat in Saccharomyces cerevisiae improved oxidative resistance by reducing intracellular ROS accumulation. The presence of multiple stress-responsive transcription factor binding sites at the promoters of antioxidative genes indicates their regulation by different transcription factors. These findings demonstrate the potential of utilizing the remarkably tolerant C. nivariensis GXAS-CN or enhancing the resistance of S. cerevisiae to improve the efficiency and cost-effectiveness of industrial fermentation processes.IMPORTANCEEnduring oxidative stress is a crucial trait for fermentation strains. The importance of this research is its capacity to advance industrial fermentation processes. Through an in-depth examination of the mechanisms behind the remarkable H2O2 resistance in Candida nivariensis GXAS-CN and the successful genetic manipulation of this strain, we open the door to harnessing the potential of the catalase CnCat for enhancing the oxidative stress resistance and performance of yeast strains. This pioneering achievement creates avenues for fine-tuning yeast strains for precise industrial applications, ultimately leading to more efficient and cost-effective biotechnological processes.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomycetales , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Catalase/metabolismo , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo
10.
Environ Sci Pollut Res Int ; 31(7): 10737-10749, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38206461

RESUMO

Water body contamination by leachate originated from dumpsites is a concern for municipal solid waste (MSW) management. In this context, this study aimed to evaluate antioxidant system alterations and oxidative and genotoxic effects in Danio rerio (zebrafish) exposed to leachate from a closed dumpsite. Groups comprising 50 fish were exposed (96 h) to different leachate concentrations (5, 15, 30, and 50%) to evaluate effects on liver and brain superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities and reduced glutathione (GSH) and metallothionein (MT) concentrations, as well as malondialdehyde (MDA) and protein carbonylation (PTC) levels. Blood genotoxicity was evaluated by the comet assay. The investigated dumpsite leachate pond presented high chloride concentrations (Cl-; 2288.4 ± 69.5 mg L-1) and high electrical conductivity (EC; 8434.0 mS cm-1), indicating the presence of leachate. Concerning Danio rerio exposure, higher SOD (37%), CAT (67%), and GST (39%) activities and higher GSH (57%) concentrations were observed in liver following exposure to 50% leachate, while decreased brain GST (42%) activities and GSH (90%) levels were observed at the same leachate concentration. A significant increase in the olive tail moment (OTM; 280%) indicative of genotoxicity in blood was observed. A principal component analysis indicated that increased enzymatic activities and high levels of both GSH and MT were not sufficient to prevent the accumulation of reactive oxygen species, resulting in PTC and genotoxicity. Therefore, leachate exposure causes sublethal Danio rerio effects, altering the antioxidant system, increasing ROS production, and leading to PTC and genotoxicity. The findings demonstrate the need to further develop sublethal level assessments in zebrafish using leachate from different sources to subsidize risk assessments regarding MSW management.


Assuntos
Perciformes , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Peixe-Zebra/metabolismo , Estresse Oxidativo , Poluentes Químicos da Água/toxicidade , Catalase/metabolismo , Dano ao DNA , Superóxido Dismutase/metabolismo , Perciformes/metabolismo , Cloretos
11.
Chem Commun (Camb) ; 60(10): 1325-1328, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38197520

RESUMO

Biocompatible Cu(II)-doped layered double hydroxide (CMA) nanoparticles were developed to combat reactive oxygen species. The 2-dimensional nanozymes showed both superoxide dismutase- and catalase-like activities in chemical assays, while proving as efficient antioxidants in the reduction of intracellular oxidative stress. The results indicate the great promise of CMA in antioxidant therapies.


Assuntos
Cobre , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Espécies Reativas de Oxigênio , Hidróxidos
12.
J Food Sci ; 89(2): 1167-1186, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38193164

RESUMO

Reuterin is a natural antifungal agent derived from certain strains of Limosilactobacillus reuteri. Our previous study revealed that 6 mM reuterin inhibited completely the conidial germination of aflatoxigenic Aspergillus flavus. This study investigated the potential molecular mechanism of reuterin in inhibiting A. flavus conidial germination, which was pre-assumed that it correlated to the inhibition of some essential enzyme activity involved in conidial germination, specifically 1,3-ß-glucan synthase, chitin synthase, and catalases (catalase, bifunctional catalase-peroxidase, and spore-specific catalase). The complex of 1,3-ß-glucan synthase and chitin synthase with reuterin had a lower binding affinity than that with the substrate. Conversely, the complex of catalases with reuterin had a higher binding affinity than that with the substrate. It was suggested that 1,3-ß-glucan synthase and chitin synthase tended to bind the substrate rather than bind reuterin. In contrast, catalases tended to bind reuterin rather than bind the substrate. Therefore, reuterin could be a potential inhibitor of catalases but may not be an inhibitor of 1,3-ß-glucan synthase and chitin synthase. In this in silico study, we predicted that the potential molecular mechanism of reuterin in inhibiting A. flavus conidial germination was due to the inhibition of catalases activities by competitively binding to the enzymes active sites, thus resulting in the accumulation of reactive oxygen species in cells, leading to cells damage. PRACTICAL APPLICATION: This in silico study revealed that reuterin is a potential inhibitor of catalases in A. flavus, thereby interfering with the antioxidant system during conidial germination. This finding shows that reuterin can be used as an antifungal agent in food or agricultural products, inhibiting conidial germination completely.


Assuntos
Aspergillus flavus , Gliceraldeído/análogos & derivados , Propano , beta-Glucanas , Catalase/metabolismo , Esporos Fúngicos/metabolismo , Antifúngicos/química , Quitina Sintase/metabolismo
13.
Free Radic Biol Med ; 213: 309-321, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262545

RESUMO

Elevated genomic instability in cancer cells suggests a possible model-scenario for their selective killing via the therapeutic delivery of well-defined levels of further DNA damage. To examine this scenario, this study investigated the potential for redox modulation of oxidatively-induced DNA damage by ascorbate in malignant melanoma (MM) cancer cells, to selectively enhance both DNA damage and MM cell killing. DNA damage was assessed by Comet and ɣH2AX assays, intracellular oxidising species by dichlorofluorescein fluorescence, a key antioxidant enzymatic defence by assessment of catalase activity and cell survival was determined by clonogenic assay. Comet revealed that MM cells had higher endogenous DNA damage levels than normal keratinocytes (HaCaT cells); this correlated MM cells having higher intracellular oxidising species and lower catalase activity, and ranked with MM cell melanin pigmentation. Comet also showed MM cells more sensitive towards the DNA damaging effects of exogenous H2O2, and that ascorbate further enhanced this H2O2-induced damage in MM cells; again, with MM cell sensitivity to induced damage ranking with degree of cell pigmentation. Furthermore, cell survival data indicated that ascorbate enhanced H2O2-induced clonogenic cell death selectively in MM cells whilst protecting HaCaT cells. Finally, we show that ascorbate serves to enhance the oxidising effects of the MM therapeutic drug Elesclomol in both established MM cells in vitro and primary cell cultures ex vivo. Together, these results suggest that ascorbate selectively enhances DNA damage and cell-killing in MM cells. This raises the option of incorporating ascorbate into clinical oxidative therapies to treat MM.


Assuntos
Melanoma , Estresse Oxidativo , Humanos , Catalase/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Ácido Ascórbico/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Oxirredução , Morte Celular , Dano ao DNA
14.
Free Radic Biol Med ; 213: 266-273, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38278309

RESUMO

Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2'-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF.


Assuntos
Antioxidantes , Febre Amarela , Humanos , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vírus da Febre Amarela/metabolismo , Glutationa/metabolismo , Estresse Oxidativo , Oxirredução , Catalase/genética , Catalase/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Dissulfeto de Glutationa/metabolismo , Hepatócitos/metabolismo , Peroxidação de Lipídeos , Glutationa Peroxidase/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/metabolismo
15.
Cardiovasc Toxicol ; 24(2): 122-132, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38165500

RESUMO

Doxorubicin is one of the most important antitumor drugs used in oncology; however, its cardiotoxic effect limits the therapeutic use and raises concerns regarding patient prognosis. Leucine is a branched-chain amino acid used in dietary supplementation and has been studied to attenuate the toxic effects of doxorubicin in animals, which increases oxidative stress. Oxidative stress in different organs can be estimated using several methods, including catalase expression analysis. This study aimed to analyze the effect of leucine on catalase levels in rat hearts after doxorubicin administration. Adult male Wistar rats were separated into two groups: Standard diet (SD) and 5% Leucine-Enriched Diet (LED). The animals had free access to diet from D0 to D28. At D14, the groups were subdivided in animals injected with Doxorubicin and animals injected with vehicle, until D28, and the groups were SD, SD + Dox, LED and LED + Dox. At D28, the animals were submitted do Transthoracic Echocardiography and euthanized. Despite Dox groups had impaired body weight gain, raw heart weight was not different between the groups. No substantial alterations were observed in macroscopic evaluation of the heart. Although, Doxorubicin treatment increased total interstitial collagen in the heart, which in addition to Type I collagen, is lower in LED groups. Western blot analysis showed that catalase expression in the heart of LED groups was lower than that in SD groups. In conclusion, leucine supplementation reduced both the precocious Dox-induced cardiac remodeling and catalase levels in the heart.


Assuntos
Cardiotoxicidade , Doxorrubicina , Humanos , Ratos , Animais , Masculino , Catalase/metabolismo , Leucina/farmacologia , Leucina/metabolismo , Leucina/uso terapêutico , Ratos Wistar , Doxorrubicina/farmacologia , Estresse Oxidativo , Suplementos Nutricionais
16.
Environ Pollut ; 344: 123402, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38272164

RESUMO

Phenazine-1-carboxylic acid (PCA) is a new type of agrochemical used to prevent plant diseases, but its effects on aquatic organisms are unclear. To comprehensively assess the impacts of PCA for aquatic organisms and its associated environmental risks, this study investigated, taking zebrafish as the research object, the toxicological mechanism of PCA by means of optical microscopy, hematoxylin and eosin (HE) staining, ultrastructural observation, physiological and biochemical testing, transcriptome sequencing, metabolome analysis, fluorescence quantitative PCR and molecular simulation. The results indicated that PCA was detrimental to zebrafish embryos, larvae and adults, with LC50 values at 96 h of 3.9093 mg/L, 8.5075 mg/L, and 13.6388 mg/L, respectively. PCA caused abnormal spontaneous movement, slowed the heart rate, delayed hatching, shortened the body length, slowed growth, and caused malformations. PCA mainly affected the brain, liver, heart, and ovaries. PCA distorted cell morphology, damaged mitochondrial membranes, disintegrated mitochondrial ridges, and dissociated nuclear membranes. PCA inhibited the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), decreased the malondialdehyde (MDA) content and disrupted antioxidant effects. The results of omics studies confirmed that PCA interfered with the transcriptional and metabolic network of zebrafish, downregulating most genes and metabolites. PCA mainly affected functions related to mitochondrial steroids, lipids, sterols, oxidoreductase activity and pathways involving cofactors, steroids, porphyrin, cytochromes, which specifically bound to targets such as panx3, agmat, and ace2. PCA was moderately toxic to zebrafish, and its usage should be strictly controlled to reduce toxic effects on aquatic organisms. The results of this study provide a new insights for ecotoxicology research.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Estresse Oxidativo , Transcriptoma , Catalase/metabolismo , Metaboloma , Esteroides/metabolismo , Poluentes Químicos da Água/metabolismo , Superóxido Dismutase/metabolismo , Embrião não Mamífero , Fenazinas
17.
Nat Commun ; 15(1): 669, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253620

RESUMO

The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.


Assuntos
Adenosina , Infecções por Helicobacter , Helicobacter pylori , Receptores Depuradores Classe E , Animais , Humanos , Camundongos , Adenosina/análogos & derivados , Catalase/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , RNA Mensageiro/genética , Receptores Depuradores Classe E/genética
18.
J Agric Food Chem ; 72(1): 810-818, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38134328

RESUMO

MnO2 is a nanozyme that inhibits the decomposition of hydrogen peroxide (H2O2) into a hydroxyl radical (OH•), thus preventing its conversion into reactive oxygen species (ROS). Oyster ferritin (GF1) is a macromolecular protein that provides uniform size and high stability and serves as an excellent template for the biomineralization of nanozyme. This study presents a unique method in which MnO2 is grown in situ in the GF1 cavity, yielding a structurally stable ferritin-based nanozyme (GF1@Mn). GF1@Mn is demonstrated to be stable at 80 °C and pH 4-8, exhibiting a higher affinity with H2O2 than many other catalases (CAT) with a Michaelis constant (Km) of 25.45 mmol/L. In vitro experiments have demonstrated the potential of GF1@Mn to enhance cell survival by reducing nitric oxide (NO) production while mitigating macrophage damage from ROS. The findings are essential to developing ferritin-based nanozymes and hold great potential for applications in functional food development.


Assuntos
Crassostrea , Manganês , Animais , Catalase/metabolismo , Manganês/metabolismo , Ferritinas/genética , Ferritinas/química , Peróxido de Hidrogênio/química , Espécies Reativas de Oxigênio/metabolismo , Compostos de Manganês , Óxidos/metabolismo
19.
Chemosphere ; 349: 140946, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103654

RESUMO

This study investigates the effects of different inorganic arsenic (As III) concentrations (0, 125, 500 and 1000 µg As/L) following two exposure times (7 and 14 days) on gills, digestive gland and muscle of scallop Aequipecten tehuelchus from Patagonia, Argentina. A biochemical approach was used to investigate oxidative stress-related parameters after different As concentrations and exposure times. Although the accumulation of As was of the same order of magnitude in all tissues, the results showed distinct tissue-specific oxidative responses to this metalloid. Furthermore, the variation in exposure time had no significant effect on As accumulation in any of the three tissues. In gills, despite no reactive oxygen and nitrogen species (RONS) were detected, there was an increase in catalase (CAT) activity and metallothionein (MT) levels. Conversely, digestive gland showed RONS production without a rise in CAT and glutathione S-transferases (GST) activities, but with an increase in MT levels. In muscle, RONS production and CAT activity kept constant or decreased, while MT levels remained unchanged. In addition, exposure time demonstrated its critical role in gills by influencing the response of CAT, GST and MT, particularly at high As concentrations, while exposure time did not affect the biochemical stress parameters in the digestive gland and muscle. Interestingly, neither concentration of As produced lipid damage, showing the effectiveness of the antioxidant mechanisms to avoid it. These results emphasize that A. tehuelchus exhibited no time-dependent effects in response to As exposure, while showing tissue-specific responses characterized by significant concentration-dependent effects of As. This study provides a comprehensive insight by considering the combined effects of time and concentration of a contaminant and distinguishing its effects on specific tissues, a dimension often overlooked in the existing literature. Subsequent studies should prioritize the analysis of additional contaminants in species with increased sensitivity.


Assuntos
Arsênio , Pectinidae , Poluentes Químicos da Água , Animais , Arsênio/análise , Argentina , Poluentes Químicos da Água/análise , Pectinidae/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Brânquias/metabolismo , Catalase/metabolismo , Peroxidação de Lipídeos
20.
Ecotoxicol Environ Saf ; 270: 115825, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38101975

RESUMO

Microplastics (MP) are harmful, causing stress in aquatic species and acting as carriers of hydrophobicity. In aquatic environments, benzo[α]pyrene (BaP) is an endocrine-disrupting chemical that accumulates in the body and causes toxic reactions in living organisms. We investigated the effects of single and combined microbead (MB) and BaP environments on goldfish antioxidant response and apoptosis. For 120 h, goldfish were exposed to single (MB10, MB100, and BaP5) and combined (MB10+BaP5 and MB100+BaP5) environments of 10 and 100 beads/L of 0.2 µm polystyrene MB and 5 µg/L BaP. We measured MB and BaP bioaccumulation as well as plasma parameters including ALT, AST, and glucose. The level of oxidative stress was determined by evaluating lipid peroxidation (LPO) and total antioxidant capacity (TAC) in plasma, as well as antioxidant-related genes for superoxide dismutase and catalase (SOD and CAT) and caspase-3 (Casp3) mRNA expression in liver tissue. The TUNEL assay was used to examine SOD in situ hybridization and apoptosis in goldfish livers. Except for the control group, plasma LPO levels increased at the end of the exposure period in all experimental groups. TAC increased up to 24 h of exposure and then maintained a similar level until the trial ended. SOD, CAT, and Casp3 mRNA expression increased substantially up to 120 h as the exposure concentration and time increased. The TUNEL assay revealed more signals and apoptotic signals in the combined exposure environments as a consequence of SOD in situ hybridization than in single exposure environments. These results suggest that combined exposure to toxic substances causes oxidative stress in organisms, which leads to apoptosis.


Assuntos
Antioxidantes , Carpa Dourada , Pirenos , Animais , Antioxidantes/metabolismo , Carpa Dourada/metabolismo , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Poliestirenos/toxicidade , Poliestirenos/metabolismo , Bioacumulação , Microesferas , Plásticos/metabolismo , Catalase/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Superóxido Dismutase/metabolismo , RNA Mensageiro/metabolismo
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