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1.
Cell Mol Life Sci ; 79(10): 521, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112236

RESUMO

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an extremely variable clinical course. We have recently shown that high catalase (CAT) expression identifies patients with an aggressive clinical course. Elucidating mechanisms regulating CAT expression in CLL is preeminent to understand disease mechanisms and develop strategies for improving its clinical management. In this study, we investigated the role of the CAT promoter rs1001179 single nucleotide polymorphism (SNP) and of the CpG Island II methylation encompassing this SNP in the regulation of CAT expression in CLL. Leukemic cells harboring the rs1001179 SNP T allele exhibited a significantly higher CAT expression compared with cells bearing the CC genotype. CAT promoter harboring the T -but not C- allele was accessible to ETS-1 and GR-ß transcription factors. Moreover, CLL cells exhibited lower methylation levels than normal B cells, in line with the higher CAT mRNA and protein expressed by CLL in comparison with normal B cells. Methylation levels at specific CpG sites negatively correlated with CAT levels in CLL cells. Inhibition of methyltransferase activity induced a significant increase in CAT levels, thus functionally validating the role of CpG methylation in regulating CAT expression in CLL. Finally, the CT/TT genotypes were associated with lower methylation and higher CAT levels, suggesting that the rs1001179 T allele and CpG methylation may interact in regulating CAT expression in CLL. This study identifies genetic and epigenetic mechanisms underlying differential expression of CAT, which could be of crucial relevance for the development of therapies targeting redox regulatory pathways in CLL.


Assuntos
Leucemia Linfocítica Crônica de Células B , Catalase/genética , Catalase/metabolismo , Metilação de DNA/genética , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo
2.
PLoS One ; 17(9): e0272928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048820

RESUMO

BACKGROUND: Postoperative abdominal adhesion is one of most common complications after abdominal operations. 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) is an adenosine 5'-monophosphate activated protein kinase (AMPK) pathway agonist that inhibits inflammation, reduces cell fibrosis and cellular reactive oxygen species (ROS) injury, promotes autophagy and mitochondrial function. This study aimed to explore the mechanism of AICAR in inhibiting adhesion formation. MATERIALS AND METHODS: Forty rats were randomly divided into five groups. All of the rats except the sham group received cecal abrasion to establish an adhesion model. The rats in the sodium hyaluronate group were treated with 2 mL sodium hyaluronate before closing the peritoneal cavity. The AICAR 1 and 2 groups were treated with 100 mg/kg and 200 mg/kg AICAR, respectively. Seven days after the operation, all of the rats were euthanized, and the adhesion condition was evaluated by Nair's system. Inflammation was assessed by Eosin-hematoxylin (HE) staining and transforming growth factor-ß (TGF-ß1) detection. Oxidative stress effect was determined by ROS, nitric oxide (NO) level, superoxide dismutase (SOD), catalase, glutathione peroxidase (Gpx) and malondialdehyde (MDA) levels in adhesion tissue. Then, Sirius red picric acid staining was used to detect the fiber thickness. Immunohistochemical staining of cytokeratin-19 (CK-19), alpha-smooth muscle actin (α-SMA) and nuclear factor erythroid 2-related factor 2 (Nrf2) was also performed. Finally, HMrSV5 cells were treated with TGF-ß1 and AICAR, the mRNA expression of E-cadherin, α-SMA and vimentin was assessed by q-PCR and cellular immunofluorescent staining. RESULTS: The rats in the AICAR-treated group had fewer adhesion formation incidences and a reduced Nair's score. The inflammation was determined by HE staining and TGF-ß1 concentration. The ROS, SOD, Catalase, Gpx, MDA levels and fiber thickness were decreased by AICAR treatments compared to the control. However, the NO production, Nrf2 levels and peritoneal mesothelial cell integrity were promoted after AICAR treatments. In vitro work, AICAR treatments reduced E-cadherin, α-SMA and vimentin mRNA level compared to that in the TGF-ß1 group. CONCLUSION: AICAR can inhibit postoperative adhesion formation by reducing inflammation, decreasing oxidative stress response and promoting peritoneal mesothelial cell repair.


Assuntos
Ribonucleosídeos , Fator de Crescimento Transformador beta1 , Aminoimidazol Carboxamida/análogos & derivados , Animais , Caderinas/metabolismo , Catalase/metabolismo , Ácido Hialurônico , Inflamação , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Ribonucleosídeos/metabolismo , Ribonucleotídeos , Superóxido Dismutase/metabolismo , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/prevenção & controle , Fator de Crescimento Transformador beta1/metabolismo , Vimentina/metabolismo
3.
Molecules ; 27(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36080244

RESUMO

Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H2O2 concentration by catalyzing its dismutation. H2O2 is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H2O2 by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H2O2 dismutation, their thermodynamic stability and their resistance to H2O2 degradation are very different, with (CATm2)Cu2 being the most promising catalyst.


Assuntos
Cobre , Peróxido de Hidrogênio , Antioxidantes , Catalase/metabolismo , Peróxido de Hidrogênio/metabolismo , Termodinâmica
4.
Environ Mol Mutagen ; 63(6): 286-295, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36053843

RESUMO

In this study, the neuroprotective action potential by ulexite (UX) (18.75 mg/L) against acetylferrocene (AFC) (3.82 mg/L) induced neurotoxicity was aimed to investigate in brain tissues of Oncorhynchus mykiss. For this purpose, the effects on neurotoxicity markers, proinflammatory cytokines, antioxidant immune system, DNA, and apoptosis mechanisms were assessed on brain tissues in the 48-96  h of the 96- trial period. In this research, it was determined that brain-derived nerve cell growth factor (BDNF) level and acetylcholinesterase (AChE) activity were inhibited in the brain tissue compared to the control group by AFC. In addition, inhibition in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) values (which are antioxidant system biomarkers), and inductions in malondialdehyde (MDA) and myeloperoxidase (MPO) amounts (which are indicators of lipid peroxidation) were determined (p < 0.05) after exposure to AFC. And, while tumor necrosis factor-α (TNF-α) and IL-6 levels were increased in the AFC-exposed group, Nrf-2 levels were found to be remarkably decreased. Upregulation was also detected in 8-hydroxydeoxyguanosine (8-OHdG) and caspase-3 levels, which are related to DNA damage and apoptosis mechanism. On the contrary, UX (single/with AFC) suppressed the AChE and BDNF inhibition by AFC. Moreover, UX mitigated AFC-induced oxidative, inflammatory, and DNA damage and attenuated AFC-mediated neurotoxicity via activating Nrf2 signaling in fish. Collectively, our findings revealed that UX supplementation might exert beneficial effects and may be considered as a natural and promising neuroprotective agent against AFC-induced toxicity.


Assuntos
Fármacos Neuroprotetores , Oncorhynchus mykiss , 8-Hidroxi-2'-Desoxiguanosina , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Caspase 3/metabolismo , Caspase 3/farmacologia , Catalase/metabolismo , Compostos Ferrosos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/farmacologia , Interleucina-6/metabolismo , Malondialdeído , Fator 2 Relacionado a NF-E2 , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Peroxidase/metabolismo , Peroxidase/farmacologia , Superóxido Dismutase , Fator de Necrose Tumoral alfa
5.
Oxid Med Cell Longev ; 2022: 3820848, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36124089

RESUMO

Background: Silver nanoparticles (AgNPs) utilization is becoming increasingly popular. The existing investigation evaluates the ameliorative impact of eugenol (Eug) against the toxic influences of AgNPs on rats' liver. Methods: Sixty adult male rats were enrolled equally into control, Eug (100 mg kg-1 orally), AgNPs-low dose (1 mg kg-1 i.p), AgNPs-high dose (2 mg kg-1 i.p), Eug + AgNPs-low dose (100 mg kg-1 orally + 1 mg kg-1 i.p), and Eug + AgNPs high dose (100 mg kg-1 orally + 2 mg kg-1 i.p). All the groups were treated daily for 30 days, subsequently serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total protein, total albumin, lactate dehydrogenase (LDH), total oxidative capacity (TOC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAC), and interleukin 6 (IL-6) levels were measured; hepatic tissues superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione peroxidase (GPx) levels were evaluated; histopathology and histomorphometry were documented in the liver of all groups; and Bcl-2, P53, Caspase-3, and TNF-α reactive proteins were also immunohistochemically detected. Results: AgNPs significantly triggered oxidative stress in hepatic tissues, characterized by elevated levels of AST, ALT, ALP, LDH, TOC, MDA, TNF-α, and IL-6 correlating with considerable decline in total protein, total albumin, TAC, SOD, CAT, GSH, and GPx. These changes were paralleled with histopathological alterations remarkable by devastation of the ordinary hepatic structure, with decrease in the numbers of normal hepatocytes, elevation in the numbers of necrotic hepatocytes, periportal and centrilobular inflammatory cells, deteriorated Kupffer cells, and dilated/congested central and portal veins. Alongside, a marked diminution in Bcl-2 immunoreactivity and a significant elevation in P53, Caspase-3, and TNF-α immunoreactivities were recorded. Supplementation of AgNPs-treated animals with Eug reversed most of the biochemical, histopathological, and immunohistochemical changes. Conclusion: This study proposed that Eug has an ameliorative effect against AgNPs-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Nanopartículas Metálicas , Alanina Transaminase/metabolismo , Albuminas/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Caspase 3/metabolismo , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Eugenol/farmacologia , Eugenol/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Interleucina-6/metabolismo , Lactato Desidrogenases/metabolismo , Masculino , Malondialdeído , Nanopartículas Metálicas/toxicidade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Prata , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53
6.
BMC Plant Biol ; 22(1): 453, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131250

RESUMO

BACKGROUND: Alhagi sparsifolia (Camelthorn) is a leguminous shrub species that dominates the Taklimakan desert's salty, hyperarid, and infertile landscapes in northwest China. Although this plant can colonize and spread in very saline soils, how it adapts to saline stress in the seedling stage remains unclear so a pot-based experiment was carried out to evaluate the effects of four different saline stress levels (0, 50, 150, and 300 mM) on the morphological and physio-biochemical responses in A. sparsifolia seedlings. RESULTS: Our results revealed that N-fixing A. sparsifolia has a variety of physio-biochemical anti-saline stress acclimations, including osmotic adjustments, enzymatic mechanisms, and the allocation of metabolic resources. Shoot-root growth and chlorophyll pigments significantly decreased under intermediate and high saline stress. Additionally, increasing levels of saline stress significantly increased Na+ but decreased K+ concentrations in roots and leaves, resulting in a decreased K+/Na+ ratio and leaves accumulated more Na + and K + ions than roots, highlighting their ability to increase cellular osmolarity, favouring water fluxes from soil to leaves. Salt-induced higher lipid peroxidation significantly triggered antioxidant enzymes, both for mass-scavenging (catalase) and cytosolic fine-regulation (superoxide dismutase and peroxidase) of H2O2. Nitrate reductase and glutamine synthetase/glutamate synthase also increased at low and intermediate saline stress levels but decreased under higher stress levels. Soluble proteins and proline rose at all salt levels, whereas soluble sugars increased only at low and medium stress. The results show that when under low-to-intermediate saline stress, seedlings invest more energy in osmotic adjustments but shift their investment towards antioxidant defense mechanisms under high levels of saline stress. CONCLUSIONS: Overall, our results suggest that A. sparsifolia seedlings tolerate low, intermediate, and high salt stress by promoting high antioxidant mechanisms, osmolytes accumulations, and the maintenance of mineral N assimilation. However, a gradual decline in growth with increasing salt levels could be attributed to the diversion of energy from growth to maintain salinity homeostasis and anti-stress oxidative mechanisms.


Assuntos
Antioxidantes , Fabaceae , Antioxidantes/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Fabaceae/metabolismo , Glutamato Sintase/metabolismo , Glutamato Sintase/farmacologia , Glutamato-Amônia Ligase/metabolismo , Peróxido de Hidrogênio/metabolismo , Íons/metabolismo , Nitrogênio/metabolismo , Prolina/metabolismo , Salinidade , Plântula/metabolismo , Solo , Açúcares/metabolismo , Superóxido Dismutase/metabolismo , Água/metabolismo
7.
Biomed Res Int ; 2022: 7659765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132078

RESUMO

Background: The present study aimed to evaluate the effect of nanocurcumin and curcumin on liver transaminases, lipid profile, oxidant and antioxidant system, and pathophysiological changes in aluminium phosphide (ALP) induced hepatoxicity. Material and Methods. In this experimental study, thirty-six male Wistar rats were randomly divided into six groups curcumin (Cur), nanocurcumin (Nanocur), ALP, ALP+Cur, and ALP+Nanocur. All treatments were performed by oral gavage for seven days. After treatment, animals were sacrificed, and liver and blood samples were taken. Serum levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (AP), total bilirubin, cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) were measured by photometric methods. Total antioxidant capacity (TAC) and malondialdehyde (MDA) as parameters of oxidative stress and mRNA expression of the nonenzyme protein including Sirtuin 1 (STR1), Forkhead box protein O1 (FOXO1) and protein O3 (FOXO3), catalase (CAT), and glutathione peroxidase (GPX) as the enzyme protein in homogenized tissues have been investigated. A histologist analyzed liver tissue sections after staining with hematoxylin-eosin. Results: In the aluminium phosphide group, there was a significant increase in MDA, ALT, AST, and AP and total bilirubin, cholesterol, triglyceride, LDL, and VLDL; AST, ALT, total bilirubin, LDL, VLDL, cholesterol, and MDA were significantly decreased; and HDL and TAC were significantly increased compared to ALP (P < 0.05). In the ALP+Nanocur group, ALT, AST, ALP, total bilirubin, cholesterol, LDL, VLDL, triglyceride, and MDA were significantly decreased and HDL and TAC were increased significantly (P < 0.05). The effect of nanocurcumin on controlling serum levels of LDL, VLDL, triglyceride, and MDA in ALP-poisoned rats was significantly more than curcumin (P < 0.05). The ALP group had significant changes in genes SIRT1, FOXO1a, FOXO3a, CAT, and GPX compared to healthy controls (P < 0.05). Nanocurcumin mice expressed more SIRT1, FOXO1a, CAT, and GPX genes than controls, and curcumin-treated mice expressed more SIRT1 and FOXO1a genes (P < 0.05). Histopathological findings also indicated a more significant protective effect of nanocurcumin relative to curcumin against ALP-induced hepatotoxicity. Conclusion: Nanocurcumin significantly protects the liver against aluminum phosphide toxicity. It is suggested that nanocurcumin-based drugs be developed to reduce the toxic effects of ALP in poisoned patients.


Assuntos
Antioxidantes , Curcumina , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Compostos de Alumínio , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases , Bilirrubina/metabolismo , Catalase/metabolismo , LDL-Colesterol/metabolismo , Curcumina/metabolismo , Curcumina/farmacologia , Amarelo de Eosina-(YS)/metabolismo , Proteína Forkhead Box O1/metabolismo , Glutationa Peroxidase/metabolismo , Hematoxilina/metabolismo , Lipoproteínas HDL , Lipoproteínas VLDL/metabolismo , Lipoproteínas VLDL/farmacologia , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Oxidantes/metabolismo , Estresse Oxidativo , Fosfinas , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sirtuína 1/metabolismo , Triglicerídeos/metabolismo
8.
Fish Shellfish Immunol ; 128: 181-187, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35917888

RESUMO

The present study aimed to examine the effects of short-term exposure to ammonia on stress and oxidative responses in shrimp (Litopenaeus vannamei) and to determine whether the antioxidant system related to the regulatory role of transcription factors and stress proteins was activated. Shrimp were exposed ammonia-N at four concentrations: 0 (control), 5, 10, and 15 mg/L, for 48 h. The hepatopancreas was sampled to measure the levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO); the activities of superoxide dismutase (SOD), catalase (CAT), nitric oxide synthase (NOS); and the expression levels of GSH-px (encoding glutathione peroxidase), GST (encoding glutathione-S-transferase), HSP70 (encoding heat shock protein 70), HSP90 (encoding heat shock protein 90), p53, RELISH, and AKIRIN. We observed that exposure to a high ammonia content increased the abundance of oxidative factors (MDA, CAT, SOD, NOS, and NO), reduced the levels of GSH, and upregulated the mRNA expression levels of antioxidant genes (GSH-px and GST), stress-related genes (HSP70 and HSP90), and transcription factor genes (p53, RELISH, and AKIRIN). These results indicated that ammonia induced oxidative stress and inflammation. Both enzymatic and nonenzymatic antioxidant defense systems are involved, which might be regulated by HSPs, as well as certain transcription factors, such as p53 and nuclear factor kappa B (NF-κB), thus mounting an adaptive response to help rebalance redox homoeostasis.


Assuntos
Amônia , Penaeidae , Amônia/metabolismo , Amônia/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Oxirredução , Estresse Oxidativo , RNA Mensageiro/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo
9.
Biochim Biophys Acta Mol Cell Res ; 1869(11): 119330, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35917894

RESUMO

Peroxisomes are single-membrane organelles essential for cell metabolism including the ß-oxidation of fatty acids, synthesis of etherlipid plasmalogens, and redox homeostasis. Investigations into peroxisome biogenesis and the human peroxisome biogenesis disorders (PBDs) have identified 14 PEX genes encoding peroxins involved in peroxisome biogenesis and the mutation of PEX genes is responsible for the PBDs. Many recent findings have further advanced our understanding of the biology, physiology, and consequences of a functional deficit of peroxisomes. In this Review, we discuss cell defense mechanisms that counteract oxidative stress by 1) a proapoptotic Bcl-2 factor BAK-mediated release to the cytosol of H2O2-degrading catalase from peroxisomes and 2) peroxisomal import suppression of catalase by Ser232-phosphorylation of Pex14, a docking protein for the Pex5-PTS1 complex. With respect to peroxisome division, the important issue of how the energy-rich GTP is produced and supplied for the division process was recently addressed by the discovery of a nucleoside diphosphate kinase-like protein, termed DYNAMO1 in a lower eukaryote, which has a mammalian homologue NME3. In regard to the mechanisms underlying the pathogenesis of PBDs, a new PBD model mouse defective in Pex14 manifests a dysregulated brain-derived neurotrophic factor (BDNF)-TrkB pathway, an important signaling pathway for cerebellar morphogenesis. Communications between peroxisomes and other organelles are also addressed.


Assuntos
Peróxido de Hidrogênio , Peroxissomos , Animais , Catalase/metabolismo , Homeostase , Humanos , Mamíferos , Camundongos , Transtornos Peroxissômicos , Peroxissomos/metabolismo
10.
Fish Shellfish Immunol ; 128: 123-135, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35921936

RESUMO

Acute ammonia toxicity suppresses the immune function and enhances the inflammatory pathways in Nile tilapia. The aim of this study was to compare the effect of Bacillus strains probiotic mixture (BS) or Yucca shidigera liquid extract (YSE) alone or their combination in water treatment and in reliving toxicity of an acute ammonia exposure in Nile tilapia through the assessment of fish immune response, inflammatory pathway, oxidative stress response with respect to the histopathological changes, gene expression, enzymes levels and phagocytosis. Five groups were used; the 1st and 2nd groups fed the basal diet; the 3rd group fed basal diet with BS in water, 4th group fed basal diet and supplemented with YSE in water and 5th group received a combination of BS and YSE. After two weeks of treatments, the 2nd, 3rd, 4th, and the 5th groups were exposed to acute ammonia challenge for 72 h. Fish exposed to ammonia displayed significant decreases in RBCs, Hb, PCV, WBCs, phagocytic activity (PA) and index (PI), lysozyme activities and serum antioxidant enzymes (glutathione peroxidase (GPX) and catalase (CAT)). Also, a significant increase in Malondialdehyde (MDA), degenerative changes in the gills, hepatopancrease and spleen associated with an elevated un-ionized ammonia level. A significant restoration of the hematological parameters was observed with the use of BS, YSE or their combination. Additionally, they improved the innate immunity, antioxidant responses, and histopathological changes. At transcriptomic level, ammonia toxicity significantly lowered the mRNA transcription levels of Nuclear erythroid 2-related factor 2 (Nrf2), quinone oxidoreductase 1 (NQO-1), Heme oxygenase 1 (HO-1) and Heat shock proteins (HSP70). While nuclear factor kappa ß (NFкß), Tumor necrosis factor α (TNF-α), Interleukin 1ß (IL-1ß), and Interleukin 8 (IL8), transcription levels were increased. Interestingly, BS and YSE and their combination significantly increased the expression of these genes with the highest levels reported with BS and YSE combination. We observed that, the most pronounced restoration of some important inflammatory and immune related genes close to the control level was observed when BS-YSE mix was used. Furthermore, a restored water pH, and a maintained ammonia level to the control level were observed in this group. Otherwise, equal effects for the three treatments were observed on the assessed parameters. We recommend the used of BS-YSE mix for water ammonia treatment and relieving ammonia toxicity in fish.


Assuntos
Bacillus , Ciclídeos , Yucca , Amônia/metabolismo , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Bacillus/genética , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/metabolismo , Heme Oxigenase-1/metabolismo , Imunidade Inata , Interleucina-1beta/metabolismo , Interleucina-8 , Malondialdeído/metabolismo , Muramidase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia , Quinonas/metabolismo , Quinonas/farmacologia , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Qualidade da Água
11.
Colloids Surf B Biointerfaces ; 218: 112715, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932557

RESUMO

Photodynamic therapy (PDT) is a promising therapeutic strategy for tumor ablation by generating highly toxic reactive oxygen species (ROS) to damage DNA and other biomacromolecules. However, the local hypoxic microenvironment of the tumor and the presence of ROS-defensing system, such as the mobilization of mutt homolog 1 (MTH1) to sanitize ROS-oxidized nucleotide pool, severely limit the efficiency of PDT. Therefore, a novel tumor ablation strategy was developed that not only focused on the enhancement of ROS generation but also weakened the ROS-defensing system by inhibiting MTH1 enzyme activity. In our work, a simple one-step reduction approach was applied to enable platinum nanoparticles (Pt NPs) with catalase activity to grow in situ in the nanochannels of mesoporous silica nanoparticles (MSNs). After physical encapsulation of photosensitizer chlorin e6 (Ce6) and MTH1 inhibitor TH588, the drug loading nanoplatform was modified with an arginine-glycine-aspartic acid (RGD) functionalized liposome shell, resulting in the fabrication of amplified oxidative damage nanoplatform MSN-Pt@Ce6/TH588 @Liposome-RGD (MPCT@Li-R). The prepared MPCT@Li-R NPs could continuously catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen (O2) in tumor, thus promoting the generation of singlet oxygen during PDT process for improved oxidative damage of bases. Simultaneously, acid responsive released TH588 hindered MTH1-mediated scavenging of oxidative bases, further aggravating DNA oxidative damage. Consequently, this cascade therapy strategy exhibited excellent tumor suppression efficiency both in vitro and in vivo.


Assuntos
Nanopartículas Metálicas , Nanocompostos , Nanopartículas , Neoplasias , Fotoquimioterapia , Arginina/metabolismo , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Ácido Aspártico/uso terapêutico , Catalase/metabolismo , Linhagem Celular Tumoral , Glicina , Humanos , Peróxido de Hidrogênio/farmacologia , Lipossomos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nucleotídeos , Oligopeptídeos/farmacologia , Estresse Oxidativo , Oxigênio/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Platina/farmacologia , Platina/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/farmacologia , Oxigênio Singlete , Triazenos
12.
Chem Biodivers ; 19(9): e202200200, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35950335

RESUMO

Diabetes mellitus is a typical life threatening of disease, which generate due to the dysfunction of ß cells of pancreas. In 2014, WHO stated that 422 million people were infected with DM. The current pattern of management of diabetes included synthetic or plant based oral hypoglycemic drugs and insulin but drug resentence is become a very big issues in antidiabetic therapy. Thus, it's very earnest to discover now medication for this disease. Now the days, it is well acknowledged that diabetic patients are more prone towards covid and related complications. Thus, medical practitioners reformed the methodology of prescribing medication for covid infected antidiabetic therapy and encouraging the medication contains dual pharmacological properties. It is also well know that polyphenols specifically hold a significant role in oxidative stress and reduced the severity of many inflammatory diseases. Cucumis melo has rich history as ethano-pharmacological use in Indian subcontinent. The fruit and seed are well-known for the treatment of various diseases due to the presence of phenolics. Therefore, in this study, the combined mixture of flower and seeds were used for the extraction of polyphenolic rich extract and tested for antidiabetic activity through the antioxidant and in vivo experiments. The antioxidant potential measurement exhibited that the selected plant extract has the significant competence to down-regulate oxidative stress (DPPH scavenging IC50 at 60.7±1.05 µg/mL, ABTS IC50 at 62.15±0.50 µg/mL). Furthermore, the major polyphenolic phyto-compounds derived from the Cucumis melo were used for in silico anticovid activity, docking, and complementarity studies. The anticovid activity prognosis reflected that selected phyto-compounds amentoflavone and vanillic acid have optimal possibility to interact with 3C-like protease and through this moderate anticovid activity can be exhibit. The docking experiments established that the selected compounds have propensity to interact with protein tyrosine phosphatase 1B, 11ß-Hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, and catalase ß-glucuronidase receptor. In vivo experiments showed that 500 mg/kg, Cucumis melo extract ominously amplified body weight, plasma insulin, high-density lipoprotein levels, and biochemical markers. Furthermore, extract significantly downregulate the blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein.


Assuntos
COVID-19 , Cucumis melo , Diabetes Mellitus Experimental , Momordica , 11-beta-Hidroxiesteroide Desidrogenases , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Biomarcadores , Glicemia , Catalase/metabolismo , Colesterol , Cucumis melo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glucuronidase , Glutationa Peroxidase/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , Lipoproteínas HDL/uso terapêutico , Lipoproteínas LDL/uso terapêutico , Momordica/metabolismo , Peptídeo Hidrolases , Extratos Vegetais/química , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Superóxido Dismutase/metabolismo , Triglicerídeos , Ácido Vanílico
13.
Fish Shellfish Immunol ; 128: 574-581, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36007828

RESUMO

Nanotechnology has recently played a key role in tackling many aquacultures issues. Hence, the present study targets the evaluation of dietary inclusion of nano iron oxide (nFe2O3) on growth performance, hematology, immune-antioxidant responses, ionic regulation and expression of related genes in Nile tilapia (Oreochromis niloticus). Fish were fed supplementary nFe2O3 at rates of zero (control), 0.5, and 1 g/kg diet for 30 days. Obtained data demonstrated that nFe2O3 significantly (P < 0.05) augmented growth performance (final weight and length, body mass gain, specific growth rate, feed conversion ratio, and length gain rate). Hematological picture {RBCs, Hb, MCV, MCH and MCHC, and leukocytes interpretations (WBCs and monocytes)}; and biochemical indexes including (AST and ALT; total protein; and glucose, and cortisol) were significantly (P < 0.05) improved in nFe2O3 supplemented groups. Plasma ionic concentration was also altered with nFe2O3 supplementation, and 1g nFe2O3 revealed the most marked increase in plasma (Na+) potassium (K+) levels. Similarly, IgM, nitrous oxide (NO), and lysozyme activity, plus superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities showed a remarkable improvement in 1g nFe2O3 group compared to the control. Expression of Insulin-Like Growth Factor-1 (IGF-1) and interleukin 1-ß (IL-1ß) genes were significantly up-regulated in nFe2O3 supplemented groups. Briefly, dietary nFe2O3 inclusion had enhanced properties on growth; hemato-biochemical; immune, antioxidative profiles; and related genes expression of O. niloticus, with a recommended concentration of 1g nFe2O3.


Assuntos
Ciclídeos , Doenças dos Peixes , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Expressão Gênica , Glucose/metabolismo , Glutationa Peroxidase/metabolismo , Hidrocortisona/metabolismo , Imunoglobulina M/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-1/metabolismo , Muramidase/metabolismo , Óxido Nitroso/metabolismo , Potássio/metabolismo , Superóxido Dismutase/metabolismo
14.
Int J Mol Sci ; 23(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36012352

RESUMO

Diabetes, a chronic group of medical disorders characterized byhyperglycemia, has become a global pandemic. Some hormones may influence the course and outcome of diabetes, especially if they potentiate the formation of reactive oxygen species (ROS). There is a close relationship between thyroid disorders and diabetes. The main objective of this investigation was to find out whether peripheral blood mononuclear cells (PBMCs) are more prone to DNA damage by triiodothyronine (T3) (0.1, 1 and 10 µM) at various stages of progression through diabetes (obese, prediabetics, and type 2 diabetes mellitus-T2DM persons). In addition, some biochemical parameters of oxidative stress (catalase-CAT, thiobarbituric acid reactive substances-TBARS) and lactate dehydrogenase (LDH) were evaluated. PBMCs from prediabetic and diabetic patients exhibited increased sensitivity for T3 regarding elevated level of DNA damage, inhibition of catalase, and increase of TBARS and LDH. PBMCs from obese patients reacted in the same manner, except for DNA damage. The results of this study should contribute to a better understanding of the role of thyroid hormones in the progression of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Catalase/metabolismo , Dano ao DNA , Diabetes Mellitus Tipo 2/genética , Humanos , Leucócitos Mononucleares/metabolismo , Obesidade , Estresse Oxidativo , Substâncias Reativas com Ácido Tiobarbitúrico , Hormônios Tireóideos
15.
Sci Rep ; 12(1): 13958, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978015

RESUMO

Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits. Western immunoblotting, spectrophotometric, and histological methods were used in this study. Tramadol (1.5 mg/kg body weight) was administered orally to male rabbits for up to three months (three times/week), and after pretreatment of rabbits with garlic (800 mg/kg) and/or selenium (1 mg/kg body weight) by 2 h. The present study showed that motilities, semen volumes, morphologies, sperm counts, testosterone, and estrogen levels were significantly decreased after 4, 8, and 12 weeks of tramadol treatment. In addition, the protein expressions of CYP 21A2, CYP 19, and 11A1 were down-regulated in the testes of the tramadol-treated rabbits. On the other hand, pretreatment of rabbits with garlic, selenium, and/or garlic-selenium for 2 h before administration of tramadol restored the downregulated CYP 21A2 and 11A1 to their normal levels after 12 weeks of tramadol treatment. Activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the testes of tramadol-treated rabbits. On the other hand, free radical levels were significantly increased in the testes of tramadol-treated rabbits for 12 weeks. Interestingly, such changes in the activities of antioxidant enzymes as well as free radical levels caused by tramadol were restored to their normal levels in the rabbits pretreated with either selenium, garlic, and/or their combination. Histopathological investigations showed that tramadol caused substantial vacuolization with the presence of damaged immature spermatozoid in the testes. However, selenium and garlic treatments showed an increase in healthy sperm production with normal mitotic and meiotic divisions. The present study illustrated for the first time the mechanisms of low steroid hormone levels in the testes of tramadol-treated rabbits which could be due to the downregulation of CYPs proteins, induction of oxidative stress, and inhibition of antioxidant enzyme activities. In addition, the present data showed that such toxic effects of tramadol were attenuated and restored to their normal levels after pretreatment of rabbits with garlic, selenium, and/or their combination. This finding may pave the way for a new approach to reducing the toxicity of tramadol.


Assuntos
Alho , Selênio , Tramadol , Animais , Antioxidantes/metabolismo , Aromatase/metabolismo , Biomarcadores/metabolismo , Peso Corporal , Catalase/metabolismo , Radicais Livres/metabolismo , Alho/metabolismo , Glutationa/metabolismo , Masculino , Estresse Oxidativo , Coelhos , Sementes/metabolismo , Selênio/metabolismo , Selênio/farmacologia , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testosterona/metabolismo , Tramadol/efeitos adversos
16.
Folia Med (Plovdiv) ; 64(4): 641-648, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045459

RESUMO

INTRODUCTION: Nanomedicine has recently been known as an emerging research area with promising applications in cancer diagnosis and treatment. Aside from this, gold nanoparticles (AuNPs), as one of the important components of nanomedicine, have attracted considerable attention due to their special physicochemical properties and lower toxicity than other nanoparticles. Despite the impressive advantages of AuNPs, it has not been yet determined whether oxidative stress contributes to the toxicity of AuNPs on bladder cancer. AIM: The aim of this study was to address this issue by conducting experiments in order to investigate the effects of 20 nm AuNPs on human bladder cancer 5637 cells. MATERIALS AND METHODS: The viability of 5637 cells was evaluated upon 24 hour exposure to different concentrations of AuNPs (0- 50 µg/ml) by 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. In order to evaluate oxidative stress status, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) and also activities of antioxidant enzymes including glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were all determined by colorimetric assay kits. RESULTS: The results from our experiment showed that the cytotoxicity caused by AuNPs was dose-dependent and the IC50 value was found to be 43.14 µg/ml after 24-hour exposure. Furthermore, MDA and TOS levels were significantly increased in treated cells compared to untreated cells (p.


Assuntos
Nanopartículas Metálicas , Neoplasias da Bexiga Urinária , Antioxidantes/farmacologia , Catalase/metabolismo , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo , Superóxido Dismutase/metabolismo
17.
Nat Commun ; 13(1): 4744, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35961961

RESUMO

Regenerable nanozymes with high catalytic stability and sustainability are promising substitutes for naturally-occurring enzymes but are limited by insufficient and non-selective catalytic activities. Herein, we developed single-atom nanozymes of RhN4, VN4, and Fe-Cu-N6 with catalytic activities surpassing natural enzymes. Notably, Rh/VN4 preferably forms an Rh/V-O-N4 active center to decrease reaction energy barriers and mediates a "two-sided oxygen-linked" reaction path, showing 4 and 5-fold higher affinities in peroxidase-like activity than the FeN4 and natural horseradish peroxidase. Furthermore, RhN4 presents a 20-fold improved affinity in the catalase-like activity compared to the natural catalase; Fe-Cu-N6 displays selectivity towards the superoxide dismutase-like activity; VN4 favors a 7-fold higher glutathione peroxidase-like activity than the natural glutathione peroxidase. Bioactive sutures with Rh/VN4 show recyclable catalytic features without apparent decay in 1 month and accelerate the scalp healing from brain trauma by promoting the vascular endothelial growth factor, regulating the immune cells like macrophages, and diminishing inflammation.


Assuntos
Lesões Encefálicas Traumáticas , Fator A de Crescimento do Endotélio Vascular , Catalase/metabolismo , Catálise , Glutationa Peroxidase/metabolismo , Humanos
18.
Cell Stress Chaperones ; 27(5): 545-560, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35951259

RESUMO

Cigarette smoke exposure increases the production of free radicals leading to initiation of several pathological conditions by triggering the oxidative stress and inflammatory cascade. Olive fruit owing to its unique phytochemical composition possesses antioxidant, immune modulatory, and anti-inflammatory potential. Considering the compositional alterations in olive fruits during ripening, the current experimental trail was designed to investigate the prophylactic role of green and black olives against the oxidative stress induced by cigarette smoke exposure in rats. Purposely, rats were divided into five different groups: NC (negative control; normal diet), PC [positive control; normal diet + smoke exposure (SE)], drug (normal diet + SE + citalopram), GO (normal diet + SE + green olive extract), and BO (normal diet + SE + black olive extract). Rats of all groups were exposed to cigarette smoke except "NC" and were sacrificed for collection of blood and organs after 28 days of experimental trial. The percent reduction in total oxidative stress by citalopram and green and black olive extracts in serum was 29.72, 58.69, and 57.97%, respectively, while the total antioxidant capacity increased by 30.78, 53.94, and 43.98%, accordingly in comparison to PC. Moreover, malondialdehyde (MDA) was reduced by 29.63, 42.59, and 45.70% in drug, GO, and BO groups, respectively. Likewise, green and black olive extracts reduced the leakage of hepatic enzymes in sera, alkaline phosphatase (ALP) by 23.44 and 25.80% and 35.62 and 37.61%, alanine transaminase (ALT) by 42.68 and 24.39% and 51.04 and 35.41%, and aspartate transaminase (AST) by 31.51 and 16.07% and 40.50 and 27.09% from PC and drug group, respectively. Additionally, olive extracts also maintained the antioxidant pool, i.e., superoxide dismutase, catalase, and glutathione in serum. Furthermore, histological examination revealed that olive extracts prevented the cigarette smoke-induced necrosis, pyknotic alterations, and congestion in the lung, hepatic, and renal parenchyma. Besides, gene expression analysis revealed that olive extracts and citalopram decreased the brain and lung damage caused by stress-induced upregulation of NRF-2 and MAPK signaling pathways. Hence, it can be concluded that olives (both green and black) can act as promising antioxidant in alleviating the cigarette smoke-induced oxidative stress.


Assuntos
Fumar Cigarros , Olea , Alanina Transaminase , Fosfatase Alcalina/metabolismo , Fosfatase Alcalina/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Aspartato Aminotransferases , Produtos Biológicos , Catalase/metabolismo , Citalopram/metabolismo , Citalopram/farmacologia , Frutas , Glutationa/metabolismo , Fígado/metabolismo , Malondialdeído/metabolismo , Olea/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
19.
Matern Child Health J ; 26(10): 2155-2168, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35969329

RESUMO

INTRODUCTION: Oxidative stress is closely related to the pathophysiology of gestation, where the placenta is susceptible to oxidative damage, contributing to the onset of gestational complications. Currently, few studies evaluate the use of oxidative markers for prediction of risk of gestational complications. However, there are some reports that suggest these biomarkers as potential prognostic biomarkers. Therefore, the objective of this study was to compare the biomarkers of oxidative stress from gestations with and without complications, and also evaluate the delta of variation in these markers from the first gestational trimester. MATERIAL AND METHODS: A total of 45 pregnant women were evaluated during the three gestational trimesters, of whom 15 developed gestational complications by the end of gestation. The evaluated oxidative damage markers were thiobarbituric acid reactive substances and nitric oxide dosage. Evaluation of the antioxidant system was performed by the quantification of vitamin C, sulfhydryl groups, total antioxidant capacity, plasmatic iron reduction ability, the evaluation of catalase and delta-aminolevulinate dehydratase enzymatic activity. RESULTS: According to the results, the markers of oxidative damage are increased, and the antioxidant profile decreased, in the third trimester of complicated pregnancies as compared to uncomplicated pregnancies. Moreover, the delta of variation in both oxidative damage markers and antioxidants was higher in complicated gestations as compared to uncomplicated gestations, thus suggesting a higher oxidative stress in pregnancies with complications. CONCLUSIONS: Oxidative stress parameters appear altered in pregnant women with gestational complications. The markers to oxidative stress can be possible biomarkers, helping in understanding mechanisms underlying the associations between complications during pregnancy and various health outcomes.


Assuntos
Antioxidantes , Complicações na Gravidez , Antioxidantes/metabolismo , Ácido Ascórbico , Biomarcadores , Catalase/metabolismo , Feminino , Humanos , Ferro , Óxido Nítrico , Estresse Oxidativo/fisiologia , Sintase do Porfobilinogênio/metabolismo , Gravidez , Gestantes , Substâncias Reativas com Ácido Tiobarbitúrico
20.
J Plant Physiol ; 277: 153793, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35995003

RESUMO

Salt stress-induced ethylene (ET) can influence the defence responses of plants that can be dependent on plant organs. In this work, the effects of salt stress evoked by 75 mM NaCl treatment were measured in fruits of wild-type (WT) and ET receptor-mutant Never ripe (Nr) tomato. Salt stress reduced the weight and size of fruits both in WT and Nr, which proved to be more pronounced in mutants. In addition, significantly higher H2O2 levels and lipid peroxidation were measured after the salt treatment in Nr as compared to the untreated control than in WT. ET regulated the key antioxidant enzymes, especially ascorbate peroxidase (APX), in WT but in the mutant fruits the activity of APX did not change and the superoxide dismutase and catalase activities were downregulated compared to untreated controls after salt treatment contributing to a higher degree of oxidative stress in Nr fruits. The dependency of PA metabolism on the active ET signalling was investigated for the first time in fruits of Nr mutants under salt stress. 75 mM NaCl enhanced the accumulation of spermine in WT fruits, which was not observed in Nr, but levels of putrescine and spermidine were elevated by salt stress in these tissues. Moreover, the catabolism of PAs was much stronger under high salinity in Nr fruits contributing to higher oxidative stress, which was only partially alleviated by the increased total and reduced ascorbate and glutathione pool. We can conclude that ET-mediated signalling plays a crucial role in the regulation of salt-induced oxidative stress and PA levels in tomato fruits at the mature stage.


Assuntos
Antioxidantes , Lycopersicon esculentum , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Etilenos/metabolismo , Frutas/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Lycopersicon esculentum/metabolismo , Poliaminas/metabolismo , Putrescina/metabolismo , Estresse Salino , Cloreto de Sódio/metabolismo , Cloreto de Sódio/farmacologia , Espermidina/metabolismo , Espermina/metabolismo , Superóxido Dismutase/metabolismo
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