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1.
Life Sci ; 259: 118382, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898532

RESUMO

AIM: Vancomycin (VCM) is a glycopeptide antibiotic widely used to treat serious infections caused by methicillin-resistant Staphylococcus aureus and has been associated with some severe side effects such as hepatotoxicity and nephrotoxicity. However, the underlying mechanism of VCM-induced hepatotoxicity is not yet fully understood. Therefore, the current study was designed to evaluate the protective effects of zingerone (Zin) against VCM-induced hepatotoxicity in rats. MATERIALS AND METHODS: VCM was intraperitoneally administered at a dose of 200 mg/kg body weight (b.w.) for 7 days alone and in combination with the orally administered Zin (25 and 50 mg/kg b.w). KEY FINDINGS: Zin treatment significantly improved VCM-induced hepatic lipid peroxidation, glutathione depletion, reduced antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities and liver function markers (aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase). Histopathological integrity and immunohistochemical expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the VCM-induced liver tissue were ameliorated after Zin administration. In addition, Zin reversed the changes in levels and/or activities of inflammatory and apoptotic parameters such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p53, cysteine aspartate specific protease-3 (caspase-3), cysteine aspartate specific protease-8 (caspase-8), cytochrome c, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) in the VCM-induced hepatotoxicity. SIGNIFICANCE: Collectively, these results reveal probable ameliorative role of Zin against VCM-induced hepatotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Guaiacol/análogos & derivados , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vancomicina/toxicidade , Animais , Western Blotting , Ciclo-Oxigenase 2/metabolismo , Guaiacol/uso terapêutico , Interleucina-1beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
2.
Ecotoxicol Environ Saf ; 205: 111293, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949840

RESUMO

Wastewater from printing and dyeing processes often contains aniline and high salinity, which are hazardous to aquatic species. Glycophytic plants cannot survive under high-salinity conditions, whereas halophytes grow well in such an environment. In this study, we investigated the influence of NaCl on the antioxidant level in Suaeda salsa affected by aniline stress. The seedlings showed various growth toxicity effects under different concentrations of aniline. The results showed that the effect of the aniline was more severe for the root growth compared to that for the shoot growth. Aniline exposure significantly increased the total free radicals and ·OH radicals in the plants. Suaeda salsa exposure to aniline caused oxidative stress by altering the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activity, which resulted in the overproduction of H2O2 and the inducement of lipid peroxidation. Analysis revealed that the malondialdehyde (MDA) content was enhanced after aniline exposure and that the chlorophyll content was significantly decreased. The results showed that aniline induced the production of free radicals and reactive oxygen species (ROS), and changed the antioxidant defense system. This ultimately resulted in oxidative damage in S. salsa; however, it was found that moderate salinity could mitigate the effects. In conclusion, salinity may alleviate the growth inhibition caused by aniline by regulating the antioxidant capacity of S. salsa.


Assuntos
Compostos de Anilina/toxicidade , Antioxidantes/metabolismo , Chenopodiaceae/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Poluentes Químicos da Água/toxicidade , Catalase/metabolismo , Chenopodiaceae/enzimologia , Chenopodiaceae/crescimento & desenvolvimento , Clorofila/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Plantas Tolerantes a Sal/efeitos dos fármacos , Plantas Tolerantes a Sal/enzimologia , Plantas Tolerantes a Sal/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Plântula/enzimologia , Plântula/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo
3.
Ecotoxicol Environ Saf ; 203: 110999, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888604

RESUMO

Aluminium (Al) is a key element that plays a major role in inhibiting plant growth and productivity under acidic soils. While lipids may be involved in plant tolerance/sensitivity to Al, the role of monogalactosyldiacylglycerol (MGDG) in Al response remains unknown. In this study, Arabidopsis MGDG synthase (AtMGD) mutants (mgd1, mgd2 and mgd3) and wild-type (Col-0) plants were treated with AlCl3; the effect of aluminium on root growth, aluminium distribution, plasma membrane integrity, lipid peroxidation, hydrogen peroxide content and membrane lipid compositions were analysed. Under Al stress, mgd mutants exhibited a more severe root growth inhibition, plasma membrane integrity damage and lipid peroxidation compared to Col-0. Al accumulation in root tips showed no difference between Col-0 and mutants under Al stress. Lipid analysis demonstrated that under Al treatment the MGDG content in all plants and MGDG/DGDG (digalactosyldiacylglycerol) remarkably reduced, especially in mutants impairing the stability and permeability of the plasma membrane. These results indicate that the Arabidopsis mgd mutants are hypersensitive to Al stress due to the reduction in MGDG content, and this is of great significance in the discovery of effective measures for plants to inhibit aluminium toxicity.


Assuntos
Alumínio/toxicidade , Arabidopsis/efeitos dos fármacos , Galactolipídeos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poluentes do Solo/toxicidade , Alumínio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Galactolipídeos/genética , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos de Membrana/metabolismo , Mutação , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Poluentes do Solo/metabolismo
4.
J Environ Pathol Toxicol Oncol ; 39(2): 137-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749123

RESUMO

Lung carcinogenesis is one of the main sources of cancer-related mortality globally and it is estimated that nearly 1 million people die from it every year. The 5-year survival rate of lung carcinogenesis is reported at just 15%. The aim of the current research was to investigate the immunomodulatory effect of eriocitrin against benzo(a)pyrene [B(a) P]-induced lung tumorigenesis in Swiss albino mice. The lung sarcoma was provoked through oral gavage of B(a)P (50 mg/kg body weight) two times/week for four weeks. CEA, lung weight, lipid peroxidation (LPO), body weight, immuno-globulin (IgG, IgA, and IgM), tumor incidence, serum marker enzymes (LDH, AHH, λ-GT, and 5'-NTs), hematological counts (leucocytes, lymphocytes, neutrophils, absolute numbers of lymphocytes and neutrophils), antioxidants (SOD and CAT), inflammatory modulators (IL-1ß, IL-6, and TNF-α), immune complexes (avidity index, phagocyte index, NBT reduction, and SIC) and histopathological changes were analyzed. Moreover, the status of apoptosis proteins (Bax, caspase-9, and caspase-3) and cell proliferative protein (cyclin D1 and cyclin A) expression was determined by Western blot and PCNA by immunohistochemical analysis. B(a)P-challenged cancer-bearing mice exhibited augmented levels of lipid peroxidation, tumor incidence, lung weight, CEA, serum marker enzymes, IgA, SIC, cell proliferative markers, and inflammatory cytokines with concurrent decrease in body weight, antioxidant levels, hematological counts, immunoglobulins, immune complexes, and apoptotic protein expression. The eriocitrin treatments caused significant reversion of all these marker to previous levels. Overall, the results propose the immunomodulatory prospective of eriocitrin against B(a) P-induced lung carcinogenesis on Swiss albino mice.


Assuntos
Flavanonas/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/prevenção & controle , Animais , Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Imunoglobulinas/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fagócitos/efeitos dos fármacos
5.
Ecotoxicol Environ Saf ; 204: 111005, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32738624

RESUMO

Freezing temperatures is an important stressor in the arctic regions and has a significant influence on the population dynamics and geographic distribution of terrestrial invertebrates. Toxic metals in the environment can interfere with protective cold-acclimation responses of organisms. It is therefore important to evaluate the combined effects of cold stress and environmental contaminants. Here, we aimed to investigate the effects of Hg (HgCl2) on various physiological aspects of freeze-tolerance in the earthworm (Enchytraeus albidus). We measured the levels of the cryoprotectant glucose, the glycogen content (source of glucose molecules for cryoprotection and fuel for metabolism), and changes in the composition of membrane phospholipid fatty acids (PLFA) as an indicator of lipid peroxidation. Freezing at -6 °C had no effect on survival in uncontaminated soil, however, survival of freezing in Hg contaminated soil was clearly reduced, especially at extended exposure times. Thus, the LC50 value in frozen soil decreased from 8.3 mg Hg kg-1 (when exposed for 17 days) to only 4.2 mg Hg kg-1 after 36 days' exposure indicating that combined effects of Hg and freezing became larger at prolonged exposure times. Hg caused a depletion of glycogen reserves (almost 50% at 12 mg kg-1 dry soil), but despite this effect worms were able to maintain a constant cryoprotectant level (about 0.12 mg glucose mg-1 dry weight) at all Hg concentrations. Hg had clear negative effects on the proportion of unsaturated PLFAs, which could be an indication of lipid peroxidation. Since a high proportion of unsaturated fatty acids in the membrane is important for invertebrate freeze-tolerance, our results suggest that the negative effect of Hg on freeze-tolerance in E. albidus is related to degraded membrane functionality at low temperature.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Congelamento , Cloreto de Mercúrio/efeitos adversos , Oligoquetos/efeitos dos fármacos , Animais , Crioprotetores/farmacologia , Relação Dose-Resposta a Droga , Ácidos Graxos/metabolismo , Glucose/farmacologia , Glicogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Mercúrio/efeitos adversos
6.
Ecotoxicol Environ Saf ; 204: 111069, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32758696

RESUMO

We studied the absorption, cytotoxicity and oxidative stress markers of Paralytic Shellfish Toxins (PST) from three extracts from Alexandrium catenella and A. ostenfeldii, in middle Oncorhynchus mykiss intestine in vitro and ex vivo preparations. We measured glutathione (GSH) content, glutathione-S transferase (GST), glutathione reductase (GR) and catalase (CAT) enzymatic activity, and lipid peroxidation in isolated epithelium exposed to 0.13 and 1.3 µM PST. ROS production and lysosomal membrane stability (as neutral red retention time 50%, NRRT50) were analyzed in isolated enterocytes exposed to PST alone or plus 3 µM of the ABCC transport inhibitor MK571. In addition, the concentration-dependent effects of PST on NRRT50 were assayed in a concentration range from 0 to 1.3 µM PST. We studied the effects of three different PST extracts on the transport rate of the ABCC substrate DNP-SG by isolated epithelium. The extract with highest inhibition capacity was selected for studying polarized DNP-SG transport in everted and non-everted intestinal segments. We registered lower GSH content and GST activity, and higher GR activity, with no significant changes in CAT activity, lipid peroxidation or ROS level. PST exposure decreased NRRT50 in a concentration-depend manner (IC50 = 0.0045 µM), but PST effects were not augmented by addition of MK571. All the three PST extracts inhibited ABCC transport activity, but this inhibition was effective only when the toxins were applied to the apical side of the intestine and DNP-SG transport was measured at the basolateral side. Our results indicate that PST are absorbed by the enterocytes from the intestine lumen. Inside the enterocytes, these toxins decrease GSH content and inhibit the basolateral ABCC transporters affecting the normal functions of the cell. Furthermore, PST produce a strong cytotoxic effect to the enterocytes by damaging the lysosomal membrane, even at low, non-neurotoxic concentrations.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Glutationa/análogos & derivados , Mucosa Intestinal/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Saxitoxina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Catalase/metabolismo , Dinoflagelados/metabolismo , Enterócitos/efeitos dos fármacos , Enterócitos/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Mucosa Intestinal/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lisossomos/metabolismo , Frutos do Mar
7.
Ecotoxicol Environ Saf ; 205: 111175, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32836161

RESUMO

Mangroves are susceptible to contamination due to their proximity to shores and human activities. Exposure to excessive trace metals can disturb their physiological functions and may eventually lead to death. Rhizophora mucronata is a common species growing in the mangrove forests of Thailand. Previous studies have shown that seedlings of R. mucronata are tolerant of trace metal and that they accumulate a large metal content in their root tissue. However, knowledge of their tolerance mechanisms is still lacking. To elicit the role of metal detoxification and sequestration by phytochelatins (PC) in the roots of R. mucronata seedlings, the impacts of Cu and Zn exposure were assessed on 1) physiological characteristics 2) the concentration of glutathione (GSH), a precursor of PC and 3) the level of the transcripts encoding phytochelatin synthase (PCS), the key enzyme for PC biosynthesis. Seedlings of R. mucronata were exposed to Cu and Zn in a hydroponic experiment (200 mg Cu or Zn/L in 1/4× Hoagland solution containing 8‰ NaCl, single addition). We found that both trace metals were largely accumulated in the roots. Only Cu-treated seedlings showed a decrease in the photosynthetic efficiency, in line with observed toxicity symptoms (i.e. bent stems and slight wilting of leaves). Metal accumulation, however, did not induce oxidative stress in the roots as indicated by similar level of total reactive species and lipid peroxidation across treatments. The GSH content in the roots exposed to Cu was significantly reduced while no change was observed in Zn-exposed roots. Coordinated semi-quantitative PCR and RT-qPCR revealed pcs down-regulation in Cu-treated roots, whereas Zn-treated roots showed a down-regulation on day 1 and a subsequent recovery on day 5. Failure of detoxification and sequestration of excess Cu due to GSH limitation and down-regulation of pcs may lead to the phytotoxic effects observed in Cu-treated plants. Our results suggest that both GSH and PC play an important role in trace metal tolerance in R. mucronata seedlings.


Assuntos
Aminoaciltransferases/genética , Cobre/toxicidade , Glutationa/metabolismo , Rhizophoraceae/efeitos dos fármacos , Oligoelementos/metabolismo , Zinco/toxicidade , Adaptação Fisiológica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Rhizophoraceae/genética , Rhizophoraceae/metabolismo , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/metabolismo
8.
Int J Nanomedicine ; 15: 4859-4876, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764923

RESUMO

Introduction: CoenzymeQ10 (CoQ10) is a well-known antioxidant and anti-inflammatory agent with cardioprotective properties. However, clinical trials based on its oral administration have failed to provide significant effect on cardiac functionality. The main limitation of CoQ10 is based on its very low oral bioavailability and instability that limit dramatically its effects as a cardioprotective agent. Herein, we loaded CoQ10 in high bioavailable nano-emulsions (NEs) coated with chitosan or chitosan and hyaluronic acid in order to improve its performance. Methods: We tested cardioprotective and hepatoprotective effects of CoQ10-loaded nano-carriers against Doxorubicin and Trastuzumab toxicities in cardiomyocytes and liver cells through analysis of cell viability, lipid peroxidation, expression of leukotrienes, p65/NF-kB and pro-inflammatory cytokines involved in anticancer-induced cardio and hepatotoxicity. Results: Nano-carriers showed high stability and loading ability and increased cell viability both in hepatocytes and cardiomyocytes during anticancer treatments. We observed that these effects are mediated by the inhibition of lipid peroxidation and reduction of the inflammation. CoQ10-loaded nano-emulsions showed also strong anti-inflammatory effects reducing leukotriene B4 and p65/NF-κB expression and Interleukin 1ß and 6 production during anticancer treatments. Discussion: Anthracyclines and Human epidermal growth factor receptor (HER2) inhibitors have shown significant anticancer effects in clinical practice but their use is characterized by cardiotoxicity and hepatotoxicity. Nano-carriers loaded with CoQ10 showed cardio and hepatoprotective properties mediated by reduction of oxidative damages and pro-inflammatory mediators. These results set the stage for preclinical studies of cardio and hepatoprotection in HER2+ breast cancer-bearing mice treated with Doxorubicin and Trastuzumab.


Assuntos
Antraciclinas/efeitos adversos , Fígado/citologia , Miócitos Cardíacos/efeitos dos fármacos , Nanoestruturas/química , Trastuzumab/efeitos adversos , Ubiquinona/análogos & derivados , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cápsulas , Cardiotônicos/química , Cardiotônicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Feminino , Hepatócitos/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Ubiquinona/química , Ubiquinona/farmacologia
9.
Aquat Toxicol ; 227: 105588, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32861020

RESUMO

The pollution of polybrominated diphenyl ethers (PBDEs) is becoming a pressing environmental problem in aquatic environments, and its threat to aquatic organism has received much attention. In this study, Phaeodactylum tricornutum was treated with 0.8 and 4 mg L-1 2,2',4,4'-tetrabrominated biphenyl ether (BDE-47), the most toxic PBDEs, for 96 h. BDE-47 inhibited cell growth in a time- and concentration-dependent manner. Observation of cell ultrastructure suggested the damage of the chloroplasts morphology. BDE-47 also decreased the chlorophyll content and the oxygen evolution rate, and altered the performance of photosystems. Transcriptomic analysis revealed differential expression of 62 genes related to photosynthesis in BDE-47 treatments (4 mg L-1) and transcription suppression of 58 genes involved in chlorophyll synthesis, antenna proteins, oxygen evolution, electron transport and downstream carbon fixation, implying potential toxicity targets in cells. Additionally, the levels of reactive oxygen species (ROS) and lipid peroxidation increased under BDE-47 stress and were positively correlated with photosynthesis inhibition. Pretreatment with the ROS scavenger N-acetyl-l-cysteine reduced the extent of inhibition, suggesting that ROS was responsible for these effects. Another experiment with the electron transport chain inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea showed that the generation of ROS was partially blocked, primarily indicating that photosynthetic inhibition induced by BDE-47 contributed to ROS overproduction. Thus, BDE-47 inhibited the photosynthesis by down-regulating the gene expression. This change stimulated ROS production, further leading to chloroplast membrane damage to aggravate this inhibition via a feedback loop. These effects of BDE-47 had adverse outcomes on the entire physiological state and the population growth of the microalgae.


Assuntos
Diatomáceas/efeitos dos fármacos , Éteres Difenil Halogenados/toxicidade , Microalgas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Acetilcisteína/farmacologia , Clorofila/metabolismo , Diatomáceas/metabolismo , Diatomáceas/ultraestrutura , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Microalgas/metabolismo , Microalgas/ultraestrutura , Modelos Teóricos , Fotossíntese/genética
10.
Chem Biol Interact ; 330: 109231, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32853594

RESUMO

Hetero mononuclear rhenium(I) metal complexes (I-V) using different substituted indole-pyrazoline based ligands were synthesized and characterized by spectroscopic and analytical methods. The binding of the rhenium complexes to Herring sperm DNA was monitored by UV spectroscopy, viscosity measurements, and molecular docking studies; groove binding was suggested as the most possible mode and the DNA-binding constants of the complexes were evaluated. In vivo and in vitro cytotoxicity of compounds were evaluated against the brine shrimp and S. cerevisiae cells. An antimicrobial study was carried out by estimating MIC (Minimum Inhibitory Concentration) against two Gram-positive and three Gram-negative bacteria. All synthesized complexes are biologically more active than the corresponding ligands. The anti-proliferation activity of complexes was evaluated on MCF-7, HCT116, and A549 cancer cells by MTT assay. The toxicity profile of synthesized compounds was confirmed by H2O2 production by reactive oxygen species. The increased concentration of lipid peroxidation end products increased free radicals, which enhancing the oxidative stress level in living organisms and results in cell death.


Assuntos
Complexos de Coordenação/farmacologia , Indóis/química , Pirazóis/química , Rênio/química , Animais , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Artemia/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Citotoxinas/toxicidade , DNA/metabolismo , Humanos , Ligantes , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/toxicidade , Saccharomyces cerevisiae/efeitos dos fármacos
11.
J Oleo Sci ; 69(8): 929-939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759551

RESUMO

Glucosylceramide (GlcCer), a major sphingolipid in plants and fungi, is known to have food functions, such as preventing intestinal impairment and enhancing the moisture content of skin. This study investigated the influence of fermentation on the composition and function of lipophilic components containing GlcCer in plant-based foods; we compared the effects of ethanol extracts from sake rice (SR) and sake lees (SL) on colon impairment in mice. GlcCer and ceramide (Cer) levels in SL were much higher than those in SR, and GlcCer in SL contained 9-methyl-trans-4,trans-8-sphingadienine as a fungi-specific sphingoid base. 1,2-dimethylhydrazine (DMH) treatment markedly increased the formation of aberrant crypt foci (ACF) and the levels of TNF-α and lipid oxidation in mice colons. However, dietary SR or SL significantly suppressed these DMH-induced changes, and SR demonstrated stronger effects than SL. In addition, dietary SR or SL suppressed the expression of apoptotic and anti-apoptotic proteins induced by DMH treatment. This study suggests that SR or SL intake could reduce colon ACF formation via the suppression of inflammation and oxidation-induced cell cycle disturbances. When compared to SR, the weaked effects of SL rich in GlcCer may be the result of the changes in sphingolipid composition (sphingoid base and Cer) and differences in the concentration of other bioactive compounds produced or digested during fermentation.


Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Neoplasias do Colo/prevenção & controle , Glucosilceramidas/análise , Glucosilceramidas/farmacologia , Oryza/química , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Vinho/análise , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patologia , Administração Oral , Animais , Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Etanol , Feminino , Fermentação , Glucosilceramidas/administração & dosagem , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
12.
Ecotoxicol Environ Saf ; 205: 111106, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32818877

RESUMO

The uptake and depuration kinetics of diclofenac and carbamazepine alone at an environmentally relevant nominal concentration of 2 µg/L and in combination at a concentration ratio of 1:1 with total concentration of 4 µg/L were evaluated in Carassius carassius after 7 d uptake and depuration. Also, the biochemical effects of both drugs alone at nominal concentrations of 2 and 10 µg/L as well as in combination with total concentrations of 4 and 20 µg/L were investigated in Carassius carassius after 7 d exposure followed by 10 d recovery. In the single treatments, steady-state BCFs measured after the 7 d exposure were 73.05, 49.71, 38.01 and 24.93 L/kg for diclofenac and 9.25, 8.99, 5.29 and 4.11 L/kg for carbamazepine in the liver, brain, gill and muscle of Carassius carassius, respectively. Comparatively lower BCFs were measured in the tissues of Carassius carassius for both drugs in the combined treatments. Acetylcholinesterase activity in the brain was significantly induced by diclofenac while carbamazepine and the mixtures significantly inhibited it during all the exposure days as well as after the 10 d recovery in all treatments. This indicates that Carassius carassius could not recover from the neurotoxic effects caused by carbamazepine unlike the inductive effect caused by diclofenac which was recoverable after 10 days. A significant increase in the activities of 7-ethoxyresorufin O-deethylase and glutathione s-transferase for individual and mixed pharmaceuticals suggest that metabolism and detoxification of both drugs took place in the liver of Carassius carassius. Also, a significant increase in the activities of superoxide dismutase, catalase, glutathione reductase and malondialdehyde contents in the individual and mixture treatments mean that the antioxidant defence system of Carassius carassius was triggered to fight against oxidative stress but lipid peroxidation still occurred. However, Carassius carassius recovered from all these increases (superoxide dismutase, catalase, glutathione reductase and malondialdehyde) after the 10 d recovery, suggesting that oxidative damage is reversible. Our results indicate that both drugs at environmentally relevant concentrations might cause adverse effects in Carassius carassius and other fish species.


Assuntos
Carbamazepina/toxicidade , Carpas/metabolismo , Diclofenaco/toxicidade , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Carbamazepina/metabolismo , Catalase/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Diclofenaco/metabolismo , Glutationa Transferase/metabolismo , Inativação Metabólica , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Malondialdeído/metabolismo , Oxirredução , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo
13.
Food Chem ; 333: 127510, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32673958

RESUMO

Aqueous coenzyme Q10 (CoQ10) dispersions were prepared using sugary maize dendrimer-like glucan (SMDG) with solid-dispersion treatment. After measuring solubility, recovery rate and loading rate, the initial weight ratio of CoQ10:SMDG was optimized to be 1:27, with the solubility markedly increasing up 188.8-folds compared to pure CoQ10 solution. The structural characterizations of CoQ10-SMDG formulation showed crystal CoQ10 was entrapped in SMDG matrix for amorphous state, associated with the strong interactions with glucan chains. The antioxidant activity of CoQ10-SMDG was assessed via DPPH and FRAP assay. DPPH scavenging activity and FRAP value of it were as high as 95.1% and 0.87 mM, respectively. The cellular uptake of CoQ10 in CoQ10-SMDG group was significantly higher than that of natural CoQ10. CoQ10-SMDG also exhibited significant protective effects against cellular damage in H2O2-induced HaCaT cell model. The results indicated that dendrimer-like glucan is an excellent platform to encapsulate and improve biological activity of hydropholic compounds.


Assuntos
Antioxidantes/química , Glucanos/química , Nanopartículas/química , Ubiquinona/análogos & derivados , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dendrímeros/química , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/toxicidade , Queratinócitos/citologia , Queratinócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Tamanho da Partícula , Solubilidade , Ubiquinona/química , Ubiquinona/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-32602765

RESUMO

The purpose of this study was to identify the long-term effect of chemical exposure on the liver. Laboratory tests included alanine aminotransferase (ALT) dosage and oxidative stress tests, such as thiobarbituric acid reactive substances in plasma and superoxide dismutase (SOD) and glutathione S-transferase analysis in erythrocytes. The cross-sectional study comprised 70 workers, 30 of them exposed to organic solvents and 40 not exposed. All those exposed presented at least 5 years of exposure to solvents. Hepatitis B and C, known hepatic disease, comorbidities, use of alcohol, illicit drugs or hepatotoxic medications, smoking, body mass index >30, female sex and age (<18 or >65) were excluded from the sample. Results indicated that elevated ALT was more frequent in the exposed group compared to controls: 33% vs. 10.5%, with a statistical significance (p < 0.05). Thiobarbituric acid reactive substances were significantly elevated (p < 0.01) in the exposed group in comparison to controls. Antioxidant enzymes were more elevated in the exposed group compared to controls: SOD 7.29 (4.30-8.91) USOD/mg of protein vs. 3.48 (2.98-5.28) USOD/mg of protein and GST 2.57 µmol/min/mg of protein (1.80-4.78) vs. 1.81 µmol/min/mg of protein (1.45- 2.30) µM/min/mg of protein. The results suggest an association between exposure to organic solvents and hepatotoxicity.


Assuntos
Antioxidantes/metabolismo , Hidrocarbonetos Aromáticos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Solventes/toxicidade , Alanina Transaminase/sangue , Animais , Brasil , Estudos Transversais , Feminino , Glutationa Transferase/sangue , Humanos , Hidrocarbonetos Aromáticos/análise , Indústrias , Fígado/enzimologia , Fígado/metabolismo , Masculino , Exposição Ocupacional/análise , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Solventes/análise , Superóxido Dismutase/sangue
15.
Chem Biol Interact ; 329: 109210, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32726580

RESUMO

Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) reduces tissue injury associated with inflammation in vivo by mechanisms that are not completely understood. Here we evaluated the effect of tempol on inflammation and oxidative damage induced by acute exposure to cigarette smoke in vivo. Male C57BL/6 mice (n = 32) were divided into 4 groups (n = 8 each): 1) control group exposed to ambient air (GC), 2) animals exposed to cigarette smoke for 5 days (CSG), mice treated 3) prior or 4) concomitantly with tempol (50 mg/kg/day) and exposed to cigarette smoke for 5 days. The results showed that the total number of leukocytes and neutrophils increased in the respiratory tract and lung parenchyma of mice exposed to cigarette smoke. Likewise, MPO levels and activity as well as lipid peroxidation and lung protein nitration and carbonylation also increased. Administration of tempol before or during exposure to cigarette smoke inhibited all the above parameters. Tempol also reduced the pulmonary expression of the inflammatory cytokines Il-6, Il-1ß and Il-17 to basal levels and of Tnf-α by approximately 50%. In contrast, tempol restored Il-10 and Tgf-ß levels and enhanced the expression of Nrf2-associated genes, such as Ho-1 and Gpx2. Accordingly, total GPx activity increased in lung homogenates of tempol-treated animals. Taken together, our results show that tempol protects mouse lungs from inflammation and oxidative damage resulting from exposure to cigarette smoke, likely through reduction of leukocyte infiltration and increased transcription of some of the Nrf2-controlled genes.


Assuntos
Óxidos N-Cíclicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fumar/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/química , Interleucina-10/genética , Interleucina-10/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Nitritos/análise , Peroxidase/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Marcadores de Spin , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
16.
Life Sci ; 257: 118050, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634425

RESUMO

BACKGROUND AND PURPOSE: Early brain injury is an essential pathological process after subarachnoid hemorrhage (SAH), with many cell death modalities. Ferroptosis is a newly discovered regulated cell death caused by the iron-dependent accumulation of lipid peroxidation, which can be prevented by glutathione peroxidase 4 (GPX4). Our study aimed to investigate the role of GPX4 in neuronal cell death after experimental SAH. METHODS: In vivo experimental SAH was induced by injecting autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Meanwhile, the in vitro SAH model was performed with primary rat cortical neurons cultured in medium containing hemoglobin (Hb). Adenovirus was used to overexpress GPX4 before experimental SAH. GPX4 expression was detected by western blot and immunofluorescence experiments. Malondialdehyde (MDA) was measured to evaluate the level of lipid peroxidation. Nissl staining was employed to assess cell death in vivo, whereas lactate dehydrogenase (LDH) release was used to evaluate cell damage in vitro. The brain water content and neurological deficits were evaluated to determine brain injury. RESULTS: Endogenous GPX4 was mainly expressed in neurons, and its expression decreased at 24 h after experimental SAH. Overexpression of GPX4 significantly reduced lipid peroxidation and cell death in the experimental SAH models both in vivo and in vitro. Moreover, overexpression of GPX4 ameliorated brain edema and neurological deficits at 24 h after SAH. CONCLUSIONS: The decrease of GPX4 expression potentially plays an important role in ferroptosis during early brain injury after SAH. Overexpression of GPX4 has a neuroprotective effect after SAH.


Assuntos
Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Encéfalo/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas/etiologia , Morte Celular/efeitos dos fármacos , Modelos Animais de Doenças , Ferroptose/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Hemorragia Subaracnóidea/metabolismo
17.
Ecotoxicol Environ Saf ; 202: 110864, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610224

RESUMO

An increasing amount of Fluoranthene (Fla) and Benz(a)anthracene (BaA) is being produced and used, eventually entering the soil sediments. The accumulation of Fla and BaA will cause poisoning to typical enzymes (α-Amylase) and organisms (Eisenia fetida) in soil. However, the studies about exploring and comparing the different effects of Fla, BaA and their joint effect at different levels are rarely reported. In this paper, the different effects of Fla, BaA and their mixed pollutant on α-Amylase were evaluated and compared at the molecular level, and the effect of Fla-BaA to the antioxidant system of earthworm (Eisenia fetida) was investigated from the aspects of concentration and exposure time at the animal level. The results showed that Fla-BaA had the greatest influence on the skeleton structure and the microenvironment of amino acid residue of α-Amylase compared to Fla and BaA, and in the mixed pollutant system, the joint effect mode was additive mode. The inhibitory effect of Fla-BaA on the activity of α-Amylase was also stronger than that of the system alone. The assays at the animal level showed that low concentrations (below 5 mg/kg) of Fla-BaA increased the activity of GSH-Px and SOD while high concentrations inhibited their activity. The POD that was activated throughout the experiment period suggested its key role in the earthworm antioxidant system. Changes in T-AOC and MDA showed that long-term and high-dose of Fla-BaA exposure inhibited the antioxidant capacity of Eisenia fetida, causing lipid peroxidation and damage to cells.


Assuntos
Benzo(a)Antracenos/toxicidade , Fluorenos/toxicidade , Poluentes do Solo/toxicidade , Animais , Antracenos , Antioxidantes/metabolismo , Poluentes Ambientais/metabolismo , Poluição Ambiental , Peroxidação de Lipídeos/efeitos dos fármacos , Oligoquetos/efeitos dos fármacos , Solo/química , Testes de Toxicidade
18.
Food Chem ; 330: 127187, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32531636

RESUMO

The objective of this study was to evaluate the chemical composition and fatty acid profile of broilers fed diets containing glycerol monolaurate (GML) in place of antimicrobials. Groups: T0 group used as control; T100, T200, and T300 groups received diets supplemented with 100, 200, and 300 mg/kg of GML, respectively. The feed mixture used in the poultry feed during the four phases of the production cycle (days 1 to 7; 8 to 21; 22 to 35; and 36 to 42 of birds age) showed similar levels of protein, lipid and ash, as well as fatty acid profiles. Samples of frozen breasts from chickens slaughtered at 42 days of age were used for chemical gross composition and fatty acid analysis. We observed lower lipid levels in the meat of broilers in the T200 and T300 groups than in the T0 group. Lower lipid peroxidation occurred in the meat of animals that consumed GML in respect to control. Total saturated fatty acid percentage was lower, while total polyunsaturated fatty acid percentage was higher in the meat of broilers fed GML than in the control group. We conclude that the increase in GML concentrations alters the lipid profile of broiler meat.


Assuntos
Ácidos Graxos/química , Lauratos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Carne/análise , Monoglicerídeos/farmacologia , Ração Animal , Animais , Galinhas , Ácidos Graxos/análise
19.
Chemosphere ; 258: 127348, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32540542

RESUMO

In this work, Fe2WO6 nanoparticles were synthesized by the ultrasound-assisted precipitation method. Various conditions were applied, including the change of the pH factor and reaction time for the synthesis of nanoparticles. After confirming the synthesis of the nanoparticles by various analyzes and evaluating their size and morphology, one of the conditions for the synthesis of the nanoparticles were selected as the optimum condition. The samples were added to the growth medium of a well-known microalga, Dunaliella salina at three concentrations of 20, 40 and 80 ppm to evaluate the effect of nanoparticles on biological systems. After 10 days different biological parameters were measured and compared with those of the control sample. According to the results, at concentration of 20 ppm the number of cells, the amount of chlorophyll a, and b, and biomass increased compared to the control samples. The Carotenoid level was higher in the treatment with 40 ppm of nanoparticles than that in the control samples. Compared to the control sample, the level of lipid peroxidation and the ratio of carbohydrate to amide II showed to be higher under 80 ppm treatment of particles. According to HCA analysis, both the evaluated parameters and concentrations of nanoparticles were divided into two general categories. Overall results showed that the effect of Fe2WO6 nanoparticles on microalgae could be a dose-dependent phenomenon, so that the addition of 20 ppm nanoparticles in the culture media helped the growth and the physiological status of algae. On the other hand, the application of a higher concentration of nanoparticles negatively affects algal biology. The results showed that the algae could be successfully used to precise screen of various nanoparticles in terms of safety especially in aquatic environments and also biotechnological applications.


Assuntos
Nanopartículas Metálicas/toxicidade , Microalgas/efeitos dos fármacos , Biomassa , Biotecnologia , Carotenoides/metabolismo , Clorofila A , Peroxidação de Lipídeos/efeitos dos fármacos , Nanopartículas
20.
Prostate ; 80(12): 917-925, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32569423

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable problem of the urogenital system. The aetiopathogenesis and effective treatments for CP/CPPS are needed to be untangled. Pirfenidone is a molecule that exhibits anti-inflammatory, antifibrotic, and antioxidative stress capacities in a variety of animal experiments and clinical trials. This study was aimed to investigate the therapeutic effect of pirfenidone on CP/CPPS and to identify the mechanism responsible for it. METHODS: A CP/CPPS model was induced in rats by intraprostatic injection of complete Freund's adjuvant (CFA). Blood and prostatic tissues were harvested for assessment after the administration of pirfenidone or vehicle for 4 weeks. RESULTS: The findings revealed that pirfenidone significantly ameliorated chronic pelvic pain and inhibited prostatic inflammation and fibrosis. Further study found that pirfenidone suppressed the expression of proinflammatory mediators, including tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, IL-8. Pirfenidone exhibited a potent antioxidant capacity through improving the activities of glutathione, catalase, total superoxide dismutase, and reducing the production of malondialdehyde. Furthermore, pirfenidone also facilitated the polarization of M2 macrophages and suppressed the activation of the nuclear factor-κB (NF-κB) signaling pathway. CONCLUSIONS: Pirfenidone can exert a beneficial effect against CFA-induced CP/CPPS by anti-inflammatory, antioxidative, antifibrotic properties, and the function is mediated at least partly through the M2 polarization of macrophages and the inhibition of NF-κB signaling pathway. These findings suggest that pirfenidone holds promise as a potential therapeutic for the treatment of CP/CPPS.


Assuntos
Dor Crônica/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Prostatite/tratamento farmacológico , Piridonas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Polaridade Celular/efeitos dos fármacos , Doença Crônica/tratamento farmacológico , Dor Crônica/metabolismo , Dor Crônica/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , NF-kappa B/metabolismo , Dor Pélvica/metabolismo , Dor Pélvica/patologia , Fosforilação/efeitos dos fármacos , Prostatite/metabolismo , Prostatite/patologia , Ratos , Síndrome
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