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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.
Chemosphere ; 258: 127411, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32947668

RESUMO

Non-steroidal anti-inflammatory drugs as an important group of emerging environmental contaminants in irrigation water and soils can influence biochemical and physiological processes essential for growth and development in plants as non-target organisms. Plants are able to take up, transport, transform, and accumulate drugs in the roots. Root biomass in ten-days old pea plants was lowered by 6% already under 0.1 mg/L naproxen (NPX) due to a lowered number of lateral roots, although 0.5 mg/L NPX stimulated the total root length by 30% as against control. Higher section area (by 40%) in root tip, area of xylem (by 150%) or stele-to-section ratio (by 10%) in zone of maturation, and lower section area in zone of lateral roots (by 18%) prove the changes in primary root anatomy and its earlier differentiation at 10 mg/L NPX. Accumulated NPX (up to 10 µg/g DW at 10 mg/L) and products of its metabolization in roots increased the amounts of hydrogen peroxide (by 33%), and superoxide (by 62%), which was reflected in elevated lipid peroxidation (by 32%), disruption of membrane integrity (by 89%) and lowering both oxidoreductase and dehydrogenase activities (by up to 40%). Elevated antioxidant capacity (SOD, APX, and other molecules) under low treatments decreased at 10 mg/L NPX (both by approx. 30%). Naproxen was proved to cause changes at both cellular and tissue levels in roots, which was also reflected in their anatomy and morphology. Higher environmental loading through drugs thus can influence even the root function.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Naproxeno/toxicidade , Ervilhas/fisiologia , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo/efeitos dos fármacos , Ervilhas/efeitos dos fármacos , Raízes de Plantas
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
5.
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
6.
Ecotoxicol Environ Saf ; 205: 111314, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956866

RESUMO

Brazilian freshwater ecosystems are continuously exposed to pesticides and domestic sewage. The Uruguay River was chosen for this study because of its international importance, as it flows through Brazil, Argentina, and Uruguay. It receives contaminants such as pesticides and domestic residues. Thus, the aim of this study to assess the accumulation of pesticides in muscle of the fish Astyanax jacuhiensis, its biochemical responses, and the presence of pesticides in water. In total, seven pesticides were registered in water from both river sites. Eight pesticides were detected in fish muscle. The biochemical responses showed that brain lipid peroxidation (LPO) and protein carbonyl (PC) in A. jacuhiensis were higher in the summer. Muscle showed the highest LPO levels in the spring and the highest PC in the summer. Liver LPO and PC levels were higher in the spring and summer. In the gills, the PC was higher in the spring and the LPO in the spring and winter. In the brain and in the gills, glutathione-S-transferase activity was high in the summer and autumn. Catalase activity was lower during the winter and spring. Non-protein thiol (NPSH) levels were lower in the brain in the winter and spring. Muscle tissue showed lower NPSH in the winter (site 1). Liver NPSH showed increased levels in liver in the spring and winter (site 2). The biochemical results clearly is related to pesticides and/or to the presence of other contaminants in the water such as metals or domestic sewage. The accumulation of pesticides in fish muscle added evidence that pesticides have been used in the area surrounding the Uruguay River. In conclusion, the biomarkers assayed in the present study could be used in future investigations considering other sampling sites along Uruguay River.


Assuntos
Characidae/fisiologia , Monitoramento Ambiental , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Brasil , Characidae/metabolismo , Caraciformes/metabolismo , Caraciformes/fisiologia , Ecossistema , Brânquias/metabolismo , Peroxidação de Lipídeos , Metais/metabolismo , Praguicidas/análise , Rios/química , Estações do Ano , Poluentes Químicos da Água/análise
7.
Nature ; 585(7826): 603-608, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32939090

RESUMO

Ferroptosis-an iron-dependent, non-apoptotic cell death process-is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers1. The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions2-5. However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly understood. Here we use genome-wide CRISPR-Cas9 suppressor screens to identify the oxidative organelles peroxisomes as critical contributors to ferroptosis sensitivity in human renal and ovarian carcinoma cells. Using lipidomic profiling we show that peroxisomes contribute to ferroptosis by synthesizing polyunsaturated ether phospholipids (PUFA-ePLs), which act as substrates for lipid peroxidation that, in turn, results in the induction of ferroptosis. Carcinoma cells that are initially sensitive to ferroptosis can switch to a ferroptosis-resistant state in vivo in mice, which is associated with extensive downregulation of PUFA-ePLs. We further find that the pro-ferroptotic role of PUFA-ePLs can be extended beyond neoplastic cells to other cell types, including neurons and cardiomyocytes. Together, our work reveals roles for the peroxisome-ether-phospholipid axis in driving susceptibility to and evasion from ferroptosis, highlights PUFA-ePL as a distinct functional lipid class that is dynamically regulated during cell-state transitions, and suggests multiple regulatory nodes for therapeutic interventions in diseases that involve ferroptosis.


Assuntos
Éteres/metabolismo , Ferroptose , Peroxissomos/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Diferenciação Celular , Linhagem Celular , Éteres/química , Feminino , Edição de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Peroxidação de Lipídeos , Masculino , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Peroxissomos/genética
8.
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
9.
Ann Hematol ; 99(10): 2265-2277, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32803313

RESUMO

ß-Thalassemia is an inherited single gene disorder related to reduced synthesis of the ß-globin chain of hemoglobin. Patients with ß-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in ß-thalassemia patients. Aberrant neutrophil effector function plays a pivotal role in infection susceptibility in these patients. In severe and persistent inflammation, immature neutrophils are released from the bone marrow and are functionally different compared with mature ones. Despite some abnormalities reported for thalassemia patient's immune system, few data exist on the characterization of human neutrophils in ß-thalassemia. The aim of this study was to investigate the phenotype and function of circulating neutrophil subsets in patients with ß-thalassemia major and with ß-thalassemia intermedia divided in transfusion-dependent and non-transfusion-dependent. By the use of immunochemical and cytofluorimetric analyses, we observed that patients' CD16+ neutrophils exhibit abnormalities in their phenotype and functions and the abnormalities vary according to the clinical form of the disease and to the neutrophil subset (CD16bright and CD16dim). Abnormalities include altered surface expression of the innate immune receptor CD45, Toll-like receptor 4, and CD32, reduced ability to produce an oxidative burst, and elevated levels of membrane lipid peroxidation, especially in patients with a more severe form of the disease. Overall, our results indicating the occurrence of an immuno-senescent phenotype on circulating neutrophils from thalassemia patients suggest the usefulness of neutrophil feature assessment as a tool for better clinical management of ß-thalassemia.


Assuntos
Neutrófilos/imunologia , Talassemia beta/sangue , Adulto , Antígenos CD/sangue , Transfusão de Componentes Sanguíneos , Senescência Celular , Terapia por Quelação , Feminino , Ferritinas/sangue , Humanos , Imunofenotipagem , Quelantes de Ferro/uso terapêutico , Contagem de Leucócitos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Neutrófilos/química , Neutrófilos/classificação , Explosão Respiratória , Esplenectomia , Receptor 4 Toll-Like/sangue , Adulto Jovem , Talassemia beta/imunologia , Talassemia beta/terapia
10.
Ecotoxicol Environ Saf ; 205: 111149, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829210

RESUMO

Exposure to heavy metals was reported to be associated with heart rate variability (HRV) alteration. However, possible pathway of such association remains unclear. In this research, we investigated the possible role of lipid peroxidation in the associations between urinary heavy metals and HRV. We performed a cross-sectional study using baseline data of Wuhan-Zhuhai cohort. Urinary heavy metals (including lead, barium, antimony, cadmium, zinc, copper, iron and manganese), urinary 8-iso-prostaglandin-F2α levels (common biomarker for lipid peroxidation) and HRV indices (SDNN, r-MSSD, low frequency, high frequency and total power) were measured among 3022 participants. We conducted multivariable linear regression models to quantify associations between urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) and heavy metals or HRV indices. The potential role of 8-iso-PGF2α in the association of urinary heavy metals with HRV was evaluated through mediation analyses. After adjusting for potential confounders, urinary manganese, iron, copper, zinc, cadmium, antimony and barium were identified to be negatively associated with one or more HRV parameters. Each one-unit growth of log-transformed levels of urinary manganese, iron, copper, zinc, antimony and barium was associated with a 1.9%, 1.5%, 4.7%, 4.0%, 2.7% and 1.3% decrease in SDNN, respectively. We observed positive dose-response relationships between all eight urinary heavy metals and 8-iso-PGF2α, as well as negative association of urinary 8-iso-PGF2α with SDNN and total power (all P trend<0.05). The proportions mediated by 8-iso-PGF2α on SDNN were 4.6% for manganese, 9.3% for iron, 19.8% for antimony and 11.0% for barium. The proportions mediated by 8-iso-PGF2α on total power were 6.9% for manganese and 10.1% for cadmium (all P value < 0.05). This study suggested that urinary manganese, iron, copper, zinc, cadmium, antimony and barium were negatively associated with HRV indices. Lipid peroxidation may partly mediate the associations of urinary manganese, iron, cadmium, antimony and barium with specific HRV indices.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Frequência Cardíaca , Peroxidação de Lipídeos , Metais Pesados/toxicidade , Adulto , Antimônio , Biomarcadores/metabolismo , Cádmio , Cobre , Estudos Transversais , Dinoprosta/análogos & derivados , Exposição Ambiental/análise , Poluentes Ambientais/metabolismo , Feminino , Humanos , Ferro , Masculino , Manganês , Metais Pesados/metabolismo , Pessoa de Meia-Idade , Zinco
11.
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
12.
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
13.
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
14.
Mar Pollut Bull ; 158: 111401, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32753186

RESUMO

This work aimed to investigate effects of the ocean contamination by the sunscreen Benzophenone-3 (BP3) and acidification, caused by CO2 enrichment, to the yellow clam, Amarilladesma mactroides. Biochemical biomarkers were analyzed in tissues (gills, digestive gland, and mantle) of clams exposed to the environmental concentration of 1 µg/L BP3, at seawater natural pH (pH 8.1) and at lower pH (pH 7.6). The tissues responded in different ways considering their physiological roles. In general, BP3 altered activity of the enzymes, glutathione-S-transferase (GST) and glutathione cysteine ligase (GCL); but mostly increased the level of glutathione (GSH). These effects were enhanced by acidification, without augmenting lipid peroxidation (LPO). Carbonic anhydrase activity (CA) increased after BP3 exposure in the digestive gland and decreased in the gills at pH 7.6, while Ca2+-ATPase activity was affected by acidification only. Changing levels of these enzymes can alter shell formation and affect the bivalve maintenance in impacted environments.


Assuntos
Bivalves , Poluentes Químicos da Água , Animais , Benzofenonas , Biomarcadores , Brânquias , Concentração de Íons de Hidrogênio , Peroxidação de Lipídeos
15.
Environ Pollut ; 266(Pt 1): 115342, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32805605

RESUMO

Although human exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with in vivo oxidative damage, and hydroxyPAH metabolites have been used as biomarkers to assess PAH-induced oxidative stress, few studies have looked at the likely causative compounds for oxidative stress in humans - PAH quinones. We developed a method using pre-column derivatization - liquid chromatography-heated electrospray ionization-tandem mass spectrometry (LC-HESI-MS/MS) to analyze ortho-phenanthrene quinones (PheQs) in human urine. 1,2-PheQ and 3,4-PheQ were identified and quantified in 3 mL of human urine; their total concentrations were higher in cigarette smokers (0.79 ± 0.98 nmol/6h urine) than in nonsmokers (0.20 ± 0.98 nmol/6h urine) (p < 0.01). The total of 1,2-PheQ and 3,4-PheQ were more strongly correlated with urinary (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), a biomarker of lipid peroxidation (R2 = 0.53, p < 0.001), than the other phenanthrene metabolites including phenanthrene tetraol (PheT), phenanthrene-1,2-dihydrodiol (1,2-PheD), and total phenanthrene phenols (OHPhe), consistent with the concept that PheQs and likely other PAH quinones play a causal role in the generation of reactive oxygen species (ROS) in humans. Thus, PheQs may be suitable as biomarkers to assess human exposure to oxygenated PAH and the subsequent oxidative damage. This study provides unique support, by analysis of human urinary metabolites, for the PAH quinone mediated oxidative damage hypothesis of PAH carcinogenesis.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Peroxidação de Lipídeos , Quinonas , Espectrometria de Massas em Tandem
16.
Environ Pollut ; 266(Pt 2): 115301, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32827983

RESUMO

Evidence for effects of PM2.5 on systemic oxidative stress in pregnant women is limited, especially in early pregnancy. To estimate the associations between ambient PM2.5 exposures and biomarkers of lipid peroxidation and total antioxidant capacity (T-AOC) in women with normal early pregnancy (NEP) and women with clinically recognized early pregnancy loss (CREPL), 206 early pregnant women who had measurements of serum malondialdehyde (MDA) and T-AOC were recruited from a larger case-control study in Tianjin, China from December 2017 to July 2018. Ambient PM2.5 concentrations of eight single-day lags exposure time windows before blood collection at the women's residential addresses were estimated using temporally-adjusted land use regression models. Effects of PM2.5 exposures on percentage change in the biomarkers were estimated using multivariable linear regression models adjusted for month, temperature, relative humidity, gestational age and other covariates. Unconstrained distributed lag models were used to estimate net cumulative effects. Increased serum MDA and T-AOC were significantly associated with increases in PM2.5 at several lag exposure time windows in both groups. The net effects of each interquartile range increase in PM2.5 over the preceding 8 days on MDA were significantly higher (p < 0.001) in CREPL [52% (95% CI: 41%, 62%)] than NEP [22% (95% CI: 9%, 36%)] women. Net effects of each interquartile range increase in PM2.5 over the preceding 5 days on T-AOC were significantly lower (p = 0.010) in CREPL [14% (95% CI: 9%, 19%)] than NEP [24% (95% CI: 18%, 29%)] women. Exposure to ambient PM2.5 may induce systemic lipid peroxidation and antioxidant response in early pregnant women. More severe lipid peroxidation and insufficient antioxidant capacity associated with PM2.5 was found in CREPL women than NEP women. Future studies should focus on mechanisms of individual susceptibility and interventions to reduce PM2.5-related oxidative stress in the first trimester.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar , Antioxidantes , Biomarcadores , Estudos de Casos e Controles , China , Exposição Ambiental , Feminino , Humanos , Peroxidação de Lipídeos , Material Particulado/análise , Gravidez
17.
Environ Pollut ; 265(Pt A): 115053, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806419

RESUMO

Environmental pollution by pharmaceuticals such as diclofenac (DCF) is globally acknowledged to be a threat to the ecosystems. Nauphoeta cinerea is an important insect with valuable ecological role. The present investigation aimed to elucidate the impact of DCF on insects by assessing the behavior and antioxidant defense response in nymphs of N. cinerea exposed to DCF-contaminated food at 0, 0.5, 1.0 and 2.0 µg kg-1 feed for 42 successive days. Subsequent to exposure period, neurobehavioral analysis using video-tracking software in a novel apparatus was performed before estimation of biochemical endpoints in the head, midgut and hemolymph of the insects. Results indicated that DCF-exposed insects exhibited marked reduction in the maximum speed, total distance traveled, mobile episodes, total mobile time, body rotation, absolute turn angle and path efficiency, whereas the total freezing time was increased compared with the control. The diminution in the exploratory activities of DCF-exposed insects was substantiated by heat maps and track plots. Additionally, DCF elicited marked diminution in antioxidant enzyme and acetylcholinesterase (AChE) activities along with increase in nitric oxide (NO), reactive oxygen and nitrogen species (RONS), and lipid peroxidation (LPO) levels in the head, midgut and hemolymph of the insects. Taken together, DCF elicited neurotoxicity and oxido-inflammatory stress in exposed insects. N. cinerea may be a suitable model insect for environmental risk assessment of pharmaceuticals in non-target insect species.


Assuntos
Baratas , Diclofenaco , Animais , Antioxidantes , Ecossistema , Peroxidação de Lipídeos
18.
Ecotoxicol Environ Saf ; 202: 110916, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800251

RESUMO

Selenium (Se) at low concentration is considered benefit element to plants. The range between optimal and toxic concentration of Se is narrow and varies among plant species. This study aimed to evaluate the phenotypic, physiological and biochemical responses of four rice genotypes (BRS Esmeralda, BRSMG Relâmpago, BRS Bonança and Bico Ganga) grown hydroponically treated with sodium selenate (1.5 mM L-1). Selenium treated plants showed a dramatically decrease of soluble proteins, chlorophylls, and carotenoids concentration, resulting in the visual symptoms of toxicity characterized as leaf chlorosis and necrosis. Selenium toxicity caused a decrease on shoot and root dry weight of rice plants. Excess Se increased the oxidative stress monitored by the levels of hydrogen peroxide and lipid peroxidation. The enzymatic antioxidant system (catalase, superoxide dismutase, and ascorbate peroxidase) increased in response to Se supply. Interestingly, primary metabolism compounds such as sucrose, total sugars, nitrate, ammonia and amino acids increased in Se-treated plants. The increase in these metabolites may indicate a defense mechanism for the osmotic readjustment of rice plants to mitigate the toxicity caused by Se. However, these metabolites were not effective to minimize the damages on phenotypic traits such as leaf chlorosis and reduced shoot and root dry weight in response to excess Se. Increased sugars profile combined with antioxidant enzymes activities can be an effective biomarkers to indicate stress induced by Se in rice plants. This study shows the physiological attributes that must be taken into account for success in the sustainable cultivation of rice in environments containing excess Se.


Assuntos
Oryza/fisiologia , Selênio/toxicidade , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Clorofila/metabolismo , Peróxido de Hidrogênio/metabolismo , Hidroponia , Peroxidação de Lipídeos , Oryza/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/metabolismo , Ácido Selênico/metabolismo , Superóxido Dismutase/metabolismo
19.
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
20.
Toxicon ; 186: 109-119, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32805295

RESUMO

To investigate the effects of oral administration of probiotics consortium on lipid metabolism in aflatoxin B1 (AFB1) exposed rats, ninety female albino rats were first grouped into two: NC (control fed standard feed) and AF (fed AFB1-contaminated feed at 40 ppb). After eight weeks, baseline animals were sacrificed from both groups while the others further divided into four groups - NC treated with and without the probiotics consortium, aflatoxin treated with and without the probiotics consortium (NCT, NCC, AFT, and AFC respectively). Five animals from each group were sacrificed weekly for four weeks, with the collection of blood, liver, brain, and the small intestine. Administration of probiotics instigated significant (p < 0.05) reductions in the elevated plasma and organ lipids as well as HDL-TAG and VLDL + LDL CHO concentrations of animals exposed to AF. AF-induced hepatic lipogenesis and up-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity were also significantly (p < 0.05) attenuated following treatment with probiotics in a time-dependent manner. Moreover, neither AF nor probiotics had any effect on glycerol-3-phosphate acyltransferase. Lipid peroxidation was significantly (p < 0.05) reduced in probiotics-treated AF groups, compared to the AF-control groups. This study indicates that the probiotic consortium used synergistically ameliorated the AFB1-induced disruptions in lipid metabolism.


Assuntos
Aflatoxina B1/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Probióticos , Administração Oral , Animais , Feminino , Peroxidação de Lipídeos , Fígado , Ratos
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