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1.
Life Sci ; 248: 117475, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32119963

RESUMO

AIMS: Liver fibrosis is a crucial pathological feature which could result in cirrhosis and hepatocarcinoma. But until now, there is no favourable treatment for it. Apigenin (APG) is a flavonoid, which exhibits efficient anti-liver fibrosis activity, but its underlying mechanisms were rarely studied. So this work aims to estimate the potential therapeutic action of APG on liver fibrosis rats and to gain insight into its system-level mechanisms. MAIN METHODS: Hepatic fibrosis was induced by CCl4 in Wistar rats, and APG was given in the light of the regimen. Biochemical indexes, histopathological change and immunohistochemistry of liver were evaluated. The optimal effect group of APG was selected for further transcriptomic and proteomic analysis. KEY FINDINGS: APG ameliorated liver fibrosis via reducing the levels of AST, ALT, ALP, LDH, Hyp, TP, TB, DB, HA, LN, PCIII and IV-C, mitigating fibrosis and inflammation of liver in H&E and Masson staining. Mechanistically, APG elevated the activity of ALB, SOD and GSH-PX with reducing the level of MDA. The results of microarray and TMT revealed that 4919 genes and 4876 proteins were differentially expressed in the APG and model groups. Besides, transcriptomics and proteomics analyses unfolded 120 overlapped proteins, enriched in 111 GO terms containing apoptotic process, angiogenesis, cell migration and proliferation, etc. Meanwhile, KEGG pathway analysis showed that 26 pathways containing HIF-1/MAPK/eNOS/VEGF/PI3K/Akt signaling pathway, regulation of actin cytoskeleton and focal adhesion mostly. SIGNIFICANCE: APG can ameliorate CCl4-induced liver fibrosis via VEGF-mediated FAK phosphorylation through the MAPKs, PI3K/Akt, HIF-1, ROS, and eNOS pathways, which may hopefully become the anti-liver fibrosis activity of natural product.


Assuntos
Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Albuminas/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Bilirrubina/sangue , Tetracloreto de Carbono/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Masculino , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Proteômica/métodos , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
2.
Life Sci ; 248: 117464, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097667

RESUMO

AIMS: The present study was carried out to investigate the influences of Selenium/Zinc-Enriched probiotics (SeZnP) on growth performance, serum enzyme activity, antioxidant capability, inflammatory factors and gene expression associated with Wistar rats inflated under high ambient thermal-stress. MAIN METHODS: Sixty male rates with six-weeks of age were randomly allocated into five groups (12 per group) and fed basal diet (Control), basal diet supplemented with probiotics (P), Zinc-Enriched probiotics (ZnP, 100 mg/L), Selenium-Enriched Probiotics (SeP, 0.3 mg/L) and Selenium/Zinc-Enriched probiotics (SeZnP, 0.3 mg + 100 mg/L). The experiment lasted 30 days. Blood and Tissues samples were taken to investigate serum enzyme activity, antioxidants capability and inflammatory factors by using of commercial kits and antioxidant, heat shock and inflammatory related molecules expressions were determined by qRT-PCR. KEY FINDINGS: Data analysis revealed that thermal stress significantly increased the level of Aspartate-aminotransferase, Alanine-aminotransferase, Lactate-dehydrogenase, Creatine-kinase, blood urea nitrogen, Creatinine and Alkaline phosphatase compared to P, ZnP, SeP or SeZnP groups (P < 0.01). However, supplementation of ZnP, SeP, and SeZnP significantly enhanced glutathione content, glutathione-peroxidase & superoxide-dismutase activity, and decreased malondialdehyde content (P < 0.05). Moreover, the concentration of IL-2, IL-6 and IL-8 were significantly increased while IL-10 was significantly decreased (P < 0.05). Furthermore, the expression of GPx1 and SOD1 genes were significantly increased, but COX-2, iNOS, HSP70 and 90 mRNA levels were significantly decreased (P < 0.05). Finally, the highest influence of the mentioned parameters was observed in SeZnP supplemented group. SIGNIFICANCE: Our study suggests that SeZnP supplementation serves as possible and best nutritive than ZnP or SeP for Wistar rats raising under high ambient temperature.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Probióticos/administração & dosagem , Selênio/administração & dosagem , Zinco/administração & dosagem , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Nitrogênio da Ureia Sanguínea , Creatina Quinase/genética , Creatina Quinase/metabolismo , Creatinina/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Resposta ao Choque Térmico/genética , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
3.
Chemosphere ; 243: 125241, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995860

RESUMO

In lakes and reservoirs, harmful algal blooms and high pH have been deemed to be two important stressors related to eutrophication, especially in the case of CO2 depletion caused by dense blooms. However, the effects of these stressors on the economically important shellfish that inhabit these waters are still not well-understood. This study evaluated the combined effects of the harmful algae Microcystis aeruginosa (0%, 50%, and 100% of total dietary dry weight) and high pH (8.0, 8.5 and 9.0) on the antioxidant responses of the triangle sail mussel H. cumingii. The mussels were exposed to algae and high pH for 14 d, followed by a 7-day depuration period. Reactive oxygen species (ROS) in the mussel hemolymph, antioxidant and detoxifying enzymes, such as glutathione-S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) in the digestive glands were analyzed during the experimental period. GST, SOD and GPx activity levels and the content of GSH increased following exposure to toxic M. aeruginosa, whereas CAT activity was inhibited. pH showed no significant effects on the immune defense mechanisms and detoxification processes. However, a high pH could cause increased ROS and MDA levels, resulting in oxidative injury. After a 7-day depuration period, exposure to toxic M. aeruginosa or high pH resulted in latent effects for most of the examined parameters. The treatment group exposed to the highest pH (9.0) displayed an increased oxidation state compared with the other pH treatments (8.0 and 8.5) for the same concentrations of toxic M. aeruginosa. The trends observed for ROS, MDA, GPx, GST, SOD and GSH levels indicated that a high density of toxic algae could result in severe and continuous effects on mussel health.


Assuntos
Antioxidantes/metabolismo , Água Doce , Proliferação Nociva de Algas , Microcystis , Unionidae/fisiologia , Animais , Catalase/metabolismo , Ecotoxicologia , Eutrofização , Água Doce/química , Água Doce/microbiologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Hemolinfa/metabolismo , Concentração de Íons de Hidrogênio , Malondialdeído/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
4.
DNA Cell Biol ; 39(3): 349-354, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31905014

RESUMO

The liver is susceptible to drug toxicity due to its vital role in xenobiotic metabolism and elimination. In addition to human leukocyte antigen (HLA) variants, which were previously determined as risk factors for drug-induced liver injury (DILI) due to co-amoxiclav, other non-HLA genes may contribute to hepatotoxicity risk. In this study, the association between DILI due to co-amoxiclav and several non-HLA genes was investigated. Association of variants in candidate genes (SOD2, GPX1, GSTM1, and GSTT1) with DILI due to various drugs was reported previously in other DILI cohorts. This study examined relevance in a co-amoxiclav-DILI cohort. One hundred sixty-five co-amoxiclav DILI cases were recruited from several European countries by two different studies (DILIGEN and iDILIC). A North-East England population group (n = 334) was used as the control group. PCR assays were used to genotype for the GSTM1 and GSTT1 null alleles with TaqMan SNP genotyping assays used for SOD2 (rs4880) and GPX1 (rs1050450). Fisher's exact test was used to assess differences in significance between cases and controls. None of the studied variants (SOD2 rs4880, GPX1 rs1050450, GSTM1 null allele, and GSTT1 null allele) was significantly associated with co-amoxiclav DILI compared with the control group. No significant differences between cases and controls were seen when combined SOD2/GPX1 genotypes and GST genotypes were considered. Despite the possible functional relevance and the previously reported contribution of the selected genes to DILI, our study failed to confirm associations between the selected genes and liver injury induced by co-amoxiclav.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/toxicidade , Antibacterianos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Glutationa Peroxidase/genética , Glutationa Transferase/genética , Humanos , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/genética
5.
Ecotoxicol Environ Saf ; 190: 110119, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891835

RESUMO

Chlorothalonil is an effective fungicide used in agriculture and formulations of antifouling paints, which use and possible toxicity has been generating great concern. Thus, the present study investigated the effects of chlorothalonil on the antioxidant defense system (ADS) of the mussel Perna perna. The ADS was evaluated in gills and digestive gland after 24 h and 96 h of exposure to environmental relevant levels of chlorothalonil (0.1 and 10 µg/L). The activity of the enzymes superoxide dismutase (SOD), catalase (CAT), glutamate cysteine-ligase (GCL) and glutathione S-transferase (GST), levels of non-enzymatic defenses, represented by glutathione (GSH), and lipoperoxidation (LPO) and protein carbonyls (PCO) were evaluated. Results indicated that exposure to chlorothalonil is affecting the ADS in both tissues. While the activity of SOD increased and GST and GSH were not altered in gills, they decreased in digestive gland after 24 h of exposure to 10 µg/L of chlorothalonil. The contrasting results indicate that gills and digestive gland presented different patterns of responses after exposure to chlorothalonil. Moreover, a tissue-specific response to chlorothalonil was observed. Gills could be acting as the first line of defense, presenting higher enzymatic levels with minor effects on the parameters analyzed. On the other hand, digestive gland, with lower levels of antioxidant defenses, was the most affect organ by chlorothalonil. It also should be highlighted that the fungicide reduced the glutathione metabolism in the digestive gland, which can lead to an imbalance of the redox state within the cells of animals.


Assuntos
Antioxidantes/metabolismo , Fungicidas Industriais/toxicidade , Nitrilos/toxicidade , Perna (Organismo)/fisiologia , Animais , Catalase/metabolismo , Fungicidas Industriais/metabolismo , Brânquias/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Perna (Organismo)/efeitos dos fármacos , Superóxido Dismutase/metabolismo
6.
Ecotoxicol Environ Saf ; 190: 110107, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31901814

RESUMO

Increased malondialdehyde (MDA) levels are commonly considered an indicator of lipid peroxidation derived from oxidative stress insults promoted by exposure of fish to pollutants. However, a decrease in MDA levels after xenobiotic exposure has been also reported, an effect that is mostly attributed to enhanced antioxidant defenses. In this study, we assessed whether pollutant-mediated MDA decrease would be associated with antioxidant enhancement or with its metabolism by aldehyde dehydrogenase (ALDH) in the liver and gills of lambari (Astyanax altiparanae) exposed to diesel oil (0.001, 0.01, and 0.1 mL/L). MDA levels were decreased in the liver of lambari exposed to diesel. The activities of the antioxidant enzymes, catalase (CAT) and glutathione peroxidase (GPx), were unchanged in the liver, while that of glucose-6-phosphate dehydrogenase (G6PDH) was decreased. In contrast, levels of total glutathione (tGSH) and the activity of glutathione S-transferase (GST) were increased in the liver, which partly support antioxidant protection against lipid peroxidation. More importantly, ALDH activity increased in a concentration-dependent manner, being negatively correlated with MDA levels, indicating MDA metabolism by ALDH. In the gills, diesel exposure increased MDA and lipid hydroperoxide levels, and promoted increases in antioxidant defenses, indicating oxidative stress. Curiously, ALDH activity was undetectable in the gills, supporting the possibility of direct MDA excretion in the water by the gills. Analyses of MDA in the water revealed increased levels of MDA in the aquaria in which the fish were exposed to diesel, compared to control aquaria. A second experiment was carried out in which the fish were intraperitoneally injected with MDA (10 mg/kg) and analyzed after 1, 6, and 12 h. MDA injection caused a time-dependent decrease in hepatic MDA levels, did not alter ALDH, CAT, GPx, and GST activities, and decreased G6PDH activity and tGSH levels. In the gills, MDA injection caused a slight increase in MDA levels after 1 h, but did not alter GPx, G6PDH, and GST activities. MDA injection also enhanced CAT activity and tGSH levels in the gills. MDA concentration in water increased progressively after 1, 6, and 12 h, supporting the hypothesis of direct MDA excretion as an alternative route for MDA elimination in fish. Our results suggest that the decreased MDA levels after exposure of lambari to diesel oil pollutant probably reflects an association between enhanced antioxidant protection, MDA metabolism, and MDA excretion in water.


Assuntos
Aldeído Desidrogenase/metabolismo , Peixes/metabolismo , Gasolina/toxicidade , Malondialdeído/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Characidae/metabolismo , Brânquias/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Estresse Oxidativo , Alimentos Marinhos , Poluentes Químicos da Água/metabolismo
7.
Ecotoxicol Environ Saf ; 190: 110126, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31918251

RESUMO

Tetramethyl thiuram disulfide (thiram) is a dithiocarbamate pesticide used for crop protection and storage. But, it's widespread utilization is associated with deleterious growth plate cartilage disorder in broilers termed as avian tibial dyschondroplasia (TD). TD results in non-mineralized and less vascularized proximal tibial growth plate cartilage causing lameness and poor growth performance. This study investigated the therapeutic potential of puerarin against thiram toxicity in TD affected chickens. One-day-old broiler chickens (n = 240) were alienated into three equal groups i.e. control, TD and puerarin (n = 80) and were offered standard feed. Additionally, TD and puerarin groups were offered thiram at 50 mg/kg of feed from 4 to 7 days for TD induction followed by puerarin therapy at 120 mg/kg to puerarin group only from 8 to 18 days for TD treatment. Thiram feeding to TD and puerarin group chickens caused lameness, mortality, and increased the aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA) levels and growth plate (GP) size and upregulated HIF-1α expression. Besides, the production parameters, alkaline phosphatase (ALP), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels and the expressions of TIMP-3 and BCL-2 were decreased (p < 0.05). Puerarin alleviated lameness, enhanced angiogenesis and growth performance and serum and antioxidant enzymes, decreased apoptosis and recuperated GP width by significantly downregulating HIF-1α and upregulating the TIMP-3 and BCL-2 mRNA and protein expressions in puerarin group chickens (p < 0.05). In conclusion, the toxic effects associated with thiram can be mitigated using puerarin.


Assuntos
Fungicidas Industriais/toxicidade , Isoflavonas/farmacologia , Osteocondrodisplasias/veterinária , Tiram/toxicidade , Vasodilatadores/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Galinhas/metabolismo , Glutationa Peroxidase/metabolismo , Lâmina de Crescimento/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Malondialdeído/metabolismo , Neovascularização Patológica/induzido quimicamente , Doenças das Aves Domésticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tíbia/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-3/metabolismo
8.
Food Microbiol ; 87: 103389, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31948630

RESUMO

To overcome the deleterious effects of hydrogen peroxide, Lactobacillus plantarum elicits an adaptive response to oxidative stress. In this study, global transcriptomic analysis revealed that L. plantarum CAUH2 expanded its carbon source utilizing profile and enhanced glycolysis to produce more ATP to confront with H2O2 stress. Some antioxidant enzymes including NADH peroxidase, thioredoxin reductase and glutathione peroxidase were 6.11, 36.76 and 6.23-fold up-regulated at transcription level for H2O2 scavenging. Meanwhile, free ferrous iron (Fe2+) was maintained at low concentrations in the cytoplasm, which could limit Fenton reaction and reduce the production of hydroxyl radicals. To repair DNA lesion caused by H2O2, both base excision repair system and recombinational DNA repair pathway were employed by L. plantarum CAUH2. In addition, the expression of methionine sulfoxide reductases and thioredoxin were up-regulated to repair oxidized proteins. It is noteworthy that some transcriptional regulators (Spx, CcpA and MarR1) were predicted to participate in the adaptive response to H2O2 stress, suggesting that L. plantarum CAUH2 utilized a wide array of sensors to monitor oxidative stress and modulated the transcriptional regulation network under H2O2 stress. These findings provide novel insight into the protective mechanisms developed by L. plantarum to cope with oxidative stress.


Assuntos
Proteínas de Bactérias/genética , Peróxido de Hidrogênio/farmacologia , Lactobacillus plantarum/efeitos dos fármacos , Lactobacillus plantarum/genética , Proteínas de Bactérias/metabolismo , Perfilação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Lactobacillus plantarum/enzimologia , Lactobacillus plantarum/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidases/genética , Peroxidases/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Transcriptoma/efeitos dos fármacos
9.
Bratisl Lek Listy ; 121(1): 62-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31950841

RESUMO

AIM: The aim of this study was to determine the effect of desflurane on reproductive capacity in female rats through a study of biochemical evaluations. METHOD: After experimental procedure, the blood samples of female rats were collected, and the malondialdehyde, interleukin­1­beta, total glutathione and superoxide dismutase levels were measured to evaluate oxidative stress. In addition to biochemical evaluations, the reproductive performance of the experimental groups was also examined. RESULTS: The results of our study demonstrated that in blood samples of desflurane­treated groups of rats, the parameters indicating oxidative stress and inflammation increased, and antioxidant parameters decreased (p < 0.05). It was also proven that repeated desflurane doses caused infertility in female rats, prolonged the gestation period and reduced the number of offspring. CONCLUSIONS: This study showed that recurrent desflurane application can cause infertility problems through oxidative stress in female rats (Tab. 3, Fig. 1, Ref. 25).


Assuntos
Desflurano , Infertilidade Feminina , Estresse Oxidativo , Animais , Antioxidantes , Desflurano/toxicidade , Feminino , Glutationa Peroxidase , Infertilidade Feminina/induzido quimicamente , Malondialdeído , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase
10.
J Photochem Photobiol B ; 204: 111775, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935591

RESUMO

Wogonin (5,7-dihydroxy-8-methoxy flavone), an active component isolated from the root of Scutellaria baicalensis Georgi. Neurotoxic effects of γ irradiation have been established in humans and animals. The current study was designed to evaluate whether wogonin could restrain γ irradiation-induced neurotoxicity in rats and to explore the underlying mechanisms. Rats were divided into five groups, 10 rats each. Group 1 was orally administered distilled water and served as control. Group 2 received an oral daily dose of wogonin (30 mg/kg). Rats in group 3 were exposed to a whole-body single dose of γ-irradiation. Animals in group 4 received an oral daily dose of wogonin (30 mg/kg) for 15 days then exposed to a whole-body single dose of γ-irradiation. In group 5, rats were exposed to a whole-body single dose of γ-irradiation then were orally administered a daily dose of wogonin (30 mg/kg) for 15 days. There were significant increases in malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and Interleukin 6 (IL-6) levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA and protein expression. Whereas significant decreases in reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) level as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA and protein expression in the irradiated group when compared with the relevant control. The cerebral cortex of irradiated rats showed vacuolization and nuclear pyknosis in the neuronal cells and focal gliosis. Wogonin administration pre- or post-irradiation significantly ameliorated all these previous effects. Wogonin had antioxidant and anti-inflammatory effects and ameliorated the histopathological changes in the brain.


Assuntos
Encéfalo/efeitos dos fármacos , Flavanonas/farmacologia , Raios gama , Fármacos Neuroprotetores/farmacologia , Administração Oral , Animais , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Medicamentos de Ervas Chinesas/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
Exp Parasitol ; 209: 107810, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31801691

RESUMO

Fasciolosis is a neglected tropical disease caused by the liver fluke Fasciola gigantica. The absence of successful vaccine and emerging resistance in flukes against the drug of choice, triclabendazole, has necessitated the search for alternatives including phyto-therapeutic approaches. Curcumin and thymoquinone, the active ingredients of Curcuma longa and Nigella sativa plants respectively, were first screened for their binding affinity with Glutathione-S-transferase (GST) molecule through in silico molecular docking followed by in vitro treatment of worms with varying concentrations of the test compounds. The in silico molecular docking of curcumin and thymoquinone with sigma GST revealed strong hydrogen bonding as well as hydrophobic interactions with high fitness scores but showing inter-specific differences. The in vitro treatment of F. gigantica worms with both curcumin and thymoquinone resulted in a significant increase in the generation of reactive oxygen species (ROS) whereas the level of reduced glutathione, a primary redox regulator, was found to be significantly decreased (p < 0.05). The two compounds not only inhibited the GST activity, which is an important detoxification enzyme and also a key drug/vaccine target for the control of fasciolosis but also significantly inhibited the activity of antioxidant enzymes glutathione peroxidase and glutathione reductase that are vital in maintenance of redox homeostasis. The immunohistochemistry performed using anti sigma GST polyclonal antibodies revealed that both the compounds used in the present study significantly reduced immunofluorescence in the vitellaria, developing eggs present in the ovary and the intestinal caecae indicating inhibition of GST enzyme in these regions of the worms. Further, following treatment with curcumin and thymoquinone, chromatin condensation and DNA fragmentation was also observed in F. gigantica worms. In conclusion, both curcumin and thymoquinone generated oxidative stress in the worms by production of ROS and significantly inhibiting their antioxidant and detoxification ability. The oxidative stress along with induction of apoptotic like events would compromise the survival ability of worms within the host. However, further studies are required to establish their anthelmintic potential alone and in combination with the commonly used anthelmintic drugs under in vivo conditions.


Assuntos
Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Curcumina/farmacologia , Fasciola/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Benzoquinonas/química , Búfalos , Cromatina/efeitos dos fármacos , Curcumina/química , Dano ao DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Eletroforese em Gel de Ágar , Inibidores Enzimáticos/farmacologia , Fasciola/citologia , Fasciola/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/antagonistas & inibidores , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Imuno-Histoquímica , Microscopia Confocal , Modelos Moleculares , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo
12.
J Biochem Mol Toxicol ; 34(2): e22427, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31777137

RESUMO

The study aimed to examine the effects of nobiletin on the toxicity model induced with acetaminophen (APAP). For this purpose, 24 adult male rats were equally divided into four groups. The groups were the control group (group 1); dimethyl sulfoxide only, the APAP group (group 2) received a single dose of APAP 1000 mg/kg on the 10th day of experiment; the Nobiletin group (group 3), nobiletin (10 mg/kg) for 10 days; and the APAP + Nobiletin group (group 4), nobiletin (10 mg/kg) for 10 days with a single dose of APAP (1000 mg/kg) administered on the 10th day and the experiment ended after 48 hours. At the end of the study, a significant increase in malondialdehyde, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels and a significant decrease in glutathione levels, glutathione peroxidase activities and nuclear factor erythroid-derived 2-like 2 (Nrf-2) and heme oxygenase-1 (HO-1) expressions were observed with APAP application in liver and kidney tissues. Serum aspartate transaminase (AST), alanine transaminase (ALT), urea, and creatinine levels were also significantly increased in the APAP group. However, nobiletin treatment in group 4 reversed oxidative stress and inflammatory and histopathological signs caused by APAP. It is concluded that nobiletin may be a beneficial substance that confers hepatorenal protection to APAP-induced toxicity via antioxidant and anti-inflammatory mechanisms.


Assuntos
Acetaminofen/efeitos adversos , Acetaminofen/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonas/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Creatinina/sangue , Citocinas/metabolismo , Flavonas/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Ureia/sangue
13.
J Biochem Mol Toxicol ; 34(2): e22430, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833155

RESUMO

The aim of this study was to investigate the effect of melatonin (MT) and its metabolite N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) on Alzheimer-like learning and memory impairment in rats intracerebroventricularly injected with streptozotocin (STZ). The results showed that the escape latency of the STZ group was longer than that of the control (CON), MT, and AFMK groups. Increased levels of hyperphosphorylated tau, neurofilament proteins, and malondialdehyde and decreased superoxide dismutase levels were observed in the brains of the rats from the STZ group compared with the brains of the rats from the CON, MT, AFMK high and low group. These results suggest that exogenous MT and AFMK can improve memory impairment and downregulate AD-like hyperphosphorylation induced by STZ, most likely through their antioxidation function. Meanwhile, we found that an equal dose of AFMK had a stronger effect than that of MT. Our results indicate that MT and its metabolite AFMK represent novel treatment strategies for Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico , Cinuramina/análogos & derivados , Melatonina/uso terapêutico , Memória Espacial/efeitos dos fármacos , Doença de Alzheimer/induzido quimicamente , Animais , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glutationa Peroxidase/metabolismo , Cinuramina/farmacologia , Cinuramina/uso terapêutico , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Melatonina/farmacologia , Proteínas de Neurofilamentos/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/efeitos adversos , Estreptozocina/farmacologia , Superóxido Dismutase/metabolismo , Proteínas tau/metabolismo
14.
Food Chem Toxicol ; 135: 111014, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794804

RESUMO

Chemical liver and kidney injury have become a serious concern to human. Side effects occur when they are treated with medicine. The present study evaluated the preventive effect of Cyclocarya paliurus polysaccharides (CP) on hepatic and renal injury in carbon tetrachloride (CCl4) induced mice. The results showed that CP treatment could effectively prevent H2O2-induced oxidative damage of NCTC-1469 cells. Administrated with CP could ameliorate the body weight loss and organ swelling of mice induced by the 0.2% CCl4. Compared with the model group, CP groups have beneficial effects in decreasing ALT, AST, TBA and CRE levels in serum. In addition, the expression of CYP2E1 in the liver was also significantly decline after continuous administration of CP. Moreover, pre-administration of CP can improve the antioxidant status of liver and kidney (MDA and SOD, GSH-Px). Histopathological studies also supported the improvement of CP on liver and kidney of CCl4-induced mice. These results indicate that CP may be of therapeutic value in ameliorating the hepatic and renal oxidative stress caused by CCl4, through its antioxidant properties.


Assuntos
Tetracloreto de Carbono/toxicidade , Juglandaceae/química , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Linhagem Celular , Citocromo P-450 CYP2E1/metabolismo , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Rim/metabolismo , Rim/patologia , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Superóxido Dismutase/metabolismo
15.
J Biochem Mol Toxicol ; 34(2): e22425, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31729815

RESUMO

The effect of combined administration of calcium (Ca), iron (Fe), zinc (Zn), chrysanthemum flavonoids, and meso-2,3-dimercaptosuccinic acid (DMSA) on the treatment of lead (Pb) intoxication in mice was studied. One hundred ninety female mice (SPF level, aged 18-22 days) were randomly divided into two groups as experimental animals. Mice in group I (10 mice) served as normal control animals, and were administered deionized water containing 12.5 µL/L acetate acid for 6 weeks, whereas mice in group II (180 mice) were exposed to 0.1% (wt/vol) of lead acetate in deionized water for 6 weeks and served as experimental animals. After 6 weeks of successful modeling, 180 mice from group II (lead-exposed) were divided into 18 groups of 10 mice each, 16 of which were treated by the combined administration of Ca, Fe, Zn, chrysanthemum flavonoids, and DMSA by L16 (215 ) orthogonal design. The remaining two groups were given treatment with low and high doses of DMSA, respectively. After three weeks of intervention (ig), the optimal treatment group was identified according to its blood lead level, as well as some antioxidant indices in the blood, liver, and hippocampus. The results indicated that the combined administration of Fe, Zn, chrysanthemum flavonoids, and DMSA with low dosage had the most significant effect on increasing the activities of blood delta-aminolevulinic acid dehydratase and superoxide dismutase (SOD), hepatic SOD and hippocampus nitric oxide synthase while decreasing the blood lead level, the content of hepatic malondialdehyde and hippocampus nitric oxide; this was considered the optimal treatment group. There was no difference in the level of blood hemoglobin between the optimal treatment group and the model control group (the first group of the orthogonal experiment). The activities of blood glutathione (GSH), hepatic GSH and glutathione peroxidase of the optimal treatment group were the same as other groups', and the recovery of the related indexes in the optimal effect group closely resembled the high dosage DMSA group. It can be concluded that the coadministration of Fe, Zn, and chrysanthemum flavonoids along with a low-dose DMSA effectively reduces Pb poisoning and lead-induced oxidative damage in lead-exposed mice; the result may provide a theoretical reference for the treatment of Pb poisoning.


Assuntos
Cálcio/farmacologia , Chrysanthemum/química , Flavonoides/farmacologia , Ferro/farmacologia , Intoxicação por Chumbo/tratamento farmacológico , Extratos Vegetais/farmacologia , Succímero/farmacologia , Zinco/farmacologia , Animais , Cálcio/administração & dosagem , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Flavonoides/administração & dosagem , Glutationa/sangue , Glutationa Peroxidase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ferro/administração & dosagem , Chumbo/efeitos adversos , Chumbo/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Sintase do Porfobilinogênio/sangue , Succímero/administração & dosagem , Superóxido Dismutase/sangue , Resultado do Tratamento , Zinco/administração & dosagem
16.
Sci Total Environ ; 704: 135426, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31822412

RESUMO

The brain is one of the critical organs particularly susceptible to the damaging effects of chronic arsenic poisoning and there is a growing body of evidence that suggest that oxidative stress plays a key role in the pathogenesis of neurodegenerative disorders. The aim of this present work was to comparatively assess biomarkers of oxidative stress and status of antioxidant enzyme activities in the brains of muskrats and squirrels breeding in arsenic endemic areas, specifically near the vicinity of the abandoned Giant mine site (~2 km radius), and an intermediate location approximately 20 km from the mine area and in reference locations spanning 52-105 km from the city of Yellowknife, Northwest Territories (Canada). Analysis included measurement of total arsenic and cadmium concentration in the nails, brain, and stomach content of muskrats and squirrels, in addition to biochemical evaluation of lipid peroxidation levels and antioxidant enzymes defense: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the brain tissues. The results revealed that arsenic concentration in the nails of muskrats collected closest to the vicinity of the mine area was in the range of 11 to 35.1 times higher than those from the reference site. The maximum concentration of arsenic in the nails of muskrats from the intermediate location was 47.6 times higher than the maximum concentration observed in the reference muskrats. Cadmium was generally undetected in the nails of muskrats and squirrels from the three sampling locations. Arsenic in the gut contents of muskrats from the arsenic affected area was 4.5 to 49.1 times higher than those from the reference site. Cadmium levels in the guts of muskrats from the mine area almost doubled those from the reference site. Arsenic accumulated in the nails of squirrels from the areas closest to the mine but was undetected in the squirrel nails from the reference location. The maximum arsenic levels in the stomach content of squirrels from the mine area was ~40 times higher than those from the reference site. Arsenic did not accumulate in the brains of muskrats, but cadmium was detected in a few brains of muskrats. Brains of squirrels from the mine area and intermediate locations accumulated both arsenic and cadmium. The brains of squirrels and muskrats from the arsenic affected area showed no evidence of increased lipid peroxidation compared to the animals from the reference site. However, SOD, CAT and GPx activities in the brains of animals from the arsenic endemic areas tended to be higher compared to the control sites. This is the first study documenting evidence of oxidative stress and altered antioxidant enzyme activities in brains of wild rodent population in arsenic endemic areas of Canada.


Assuntos
Arsênico/metabolismo , Encéfalo/metabolismo , Cádmio/metabolismo , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Estresse Oxidativo/fisiologia , Animais , Antioxidantes/metabolismo , Arvicolinae , Biomarcadores/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Territórios do Noroeste , Sciuridae , Superóxido Dismutase/metabolismo
17.
Bull Entomol Res ; 110(1): 34-43, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31190653

RESUMO

Gall formation is associated with multiple changes in plant cells, which still requires a better understanding. In this study, galls caused by sexual generation (♀♂) of Neuroterus quercusbaccarum (L.) (Hymenoptera: Cynipidae) on pedunculate oak trees (Quercus robur L.) were used as a model. Cytoplasmic membrane condition, concentration of hydrogen peroxide (H2O2), the activity of antioxidant enzymes and amino acid decarboxylase as well as chlorophyll fluorescence parameters were determined. Changes in physiological and biochemical parameters were analyzed in foliar tissues with galls and gall tissues themselves and compared to control. The presence of galls on oak leaves caused an increase of lipid peroxidation level. A significant decline in H2O2 and TBARS content with the reduction of guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) activity were observed in gall tissues. The activity amino acid decarboxylase, i.e., LDC, ODC and TyDC varied between samples, which may affect the content of amino acids. The presence of N. quercusbaccarum galls caused an insignificant increase of the chlorophylls, carotenoids and anthocyanin contents, while the content of pigments and their ratios in gall tissues was extremely low. Moreover, photosynthetic parameters (F0, Fm, Fv/Fm, Y, qP) were significantly decreased. Data generated in this study indicate that the development of N. quercusbaccarum galls on pedunculate oak leaves has a negative effect on host plant related to the disruption of cell membrane integrity, disturbance of photosynthesis and reduction of the antioxidant potential of the host plant.


Assuntos
Interações Hospedeiro-Parasita , Folhas de Planta/parasitologia , Tumores de Planta , Quercus/parasitologia , Vespas/fisiologia , Animais , Membrana Celular/fisiologia , Feminino , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Masculino , Estresse Oxidativo , Fotossíntese , Pigmentação , Folhas de Planta/fisiologia , Quercus/fisiologia
18.
Curr Med Chem ; 27(3): 423-449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-29421998

RESUMO

Selenium is a trace element, nutritionally classified as an essential micronutrient, involved in maintaining the correct function of several enzymes incorporating the selenocysteine residue, namely the selenoproteins. The human selenoproteome including 25 proteins is extensively described here. The most relevant selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases are required for the proper cellular redox homeostasis as well as for the correct thyroid function, thus preventing oxidative stress and related diseases. This review summarizes the main advances on oxidative stress with a focus on selenium metabolism and transport. Moreover, thyroid-related disorders are discussed, considering that the thyroid gland contains the highest selenium amount per gram of tissue, also for future possible therapeutic implication.


Assuntos
Estresse Oxidativo , Glutationa Peroxidase , Humanos , Selênio , Selenoproteínas , Glândula Tireoide
19.
Aquat Toxicol ; 219: 105361, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862548

RESUMO

Given the toxicity of trace metals, their concentration, speciation and bioavailability serve to induce various plant detoxification processes, which themselves are specific to several parameters like plant species, tissue type and developmental stage. In this study, Myriophyllum alterniflorum (or alternate watermilfoil) enzyme activities (ascorbate peroxidase, catalase, glutathione peroxidase and superoxide dismutase) from in vitro cultures was measured over 27 days in response to copper (Cu) or cadmium (Cd) stress. These enzymes are unique to reactive oxygen species (ROS) scavenging (mainly hydrogen peroxide H2O2 and superoxide anion O2-) and moreover showed specific or unspecific activity profiles, depending on the metal concentrations used. Our results suggest a higher-priority protection of chloroplasts during the initial days of exposure to both metals. At the same time, the increased catalase activity could indicate an H2O2 diffusion in peroxisome in order to protect other organelles from ROS accumulation. However, as opposed to the Cd effects, high Cu concentrations appear to induce a "limited oxidative threshold" for some antioxidant enzymes, which could suggest an ion absorption competition between Cu2+ and Fe2+. In spite of an overall analysis conducted of the scavenging processes occurring in plant cells, biochemical analyses still yielded relevant indications regarding the watermilfoil strategies used for ROS management.


Assuntos
Antioxidantes/metabolismo , Cádmio/toxicidade , Cobre/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Saxifragales/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Peróxido de Hidrogênio/metabolismo , Inativação Metabólica , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Saxifragales/enzimologia , Superóxido Dismutase/metabolismo , Oligoelementos
20.
Ecotoxicol Environ Saf ; 190: 110086, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31864119

RESUMO

Glyphosate-based herbicides (GBH), including Roundup®, are the most used herbicides in agricultural and non-agricultural areas, which can reach aquatic environments through drift during application or surface runoff. Some studies, mostly in fish, demonstrated that GBH caused oxidative stress in non-target animals. However, only few information is available on the GBH effects in the antioxidant and stress proteins of many other organisms, such as freshwater crustaceans. Thus, we aimed to investigate the effects of environmentally relevant GBH concentrations on the relative transcript expression (RTE) of the superoxide dismutase (sod1), catalase (cat), selenium-dependent glutathione peroxidase (gpx), glutathione-S-transferase (gst), thioredoxin (txn), heat shock protein (hsp70 and hsp90) in the hepatopancreas of the ecologically important freshwater prawn Macrobrachium potiuna. Moreover, this study aimed to assess the gender-differences responses to GBH exposure. Male and female prawns were exposed to three Roundup WG® concentrations (0.0065, 0.065 and 0.28 mg of glyphosate/L) and a control group (0.0 mg/L) for 7 and 14 days. In general, males had an under-expression of the studied genes, indicating an oxidative stress and possible accumulation of ROS in the hepatopancreas. In the opposite, females had an overexpression of the same genes, indicating a more robust antioxidant system, in order to cope with the possible ROS increase after Roundup WG® exposure. Therefore, results confirmed that gender could be a confounding factor in ecotoxicological assessment of GBH effects. Additionally, this work highlights that sod1, cat, gpx, gst, txn, hsp70 and hsp90 gene expressions seem to be useful biomarkers to investigate the oxidative stress caused by Roundup WG® in Macrobrachium sp.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Palaemonidae/fisiologia , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Catalase/metabolismo , Feminino , Água Doce , Expressão Gênica , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Glicina/toxicidade , Hepatopâncreas/efeitos dos fármacos , Herbicidas/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Palaemonidae/efeitos dos fármacos , Selênio/metabolismo , Superóxido Dismutase/metabolismo
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