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1.
Life Sci ; 270: 119146, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545199

RESUMO

Deferasirox (DFX) was formulated into oil-in-water microemulsions in the presence of pluronicto improve its oral bioavailability. The size of the DFX-loadedmicroemulsions system measured by dynamic light scattering (DLS) was about 9 nm. The anti-proliferative and anti-lipid peroxidation effects of DFX and DFX-loaded microemulsions were assessed on Human umbilical vein endothelial (HUVEC) cells. Our in vitro results showed that HUVEC cells are more susceptible to free DFX as compared to DFX-loaded microemulsions. Although both free and encapsulated DFX attenuated FeCl3-induced lipid peroxidation, after 6 and 12 h treatment, DFX-loaded microemulsions did not appear a better ameliorator than DFX. To compare the in vivo efficacy of free DFX and DFX-loaded microemulsions in iron- intoxicated rats, the animals were orally administered with 25 mg/kg DFX, or 25 mg/kg DFX microemulsions, respectively. In vivo gavage handling of free DFX significantly increased serum biochemical parameters. There was also a significant increase in lipid peroxidation in rats who received free DFX compared to those in the control rats. Treatment with DFX-loaded microemulsions restored the elevated levels of serum AST, ALT, and creatinine levels and also reduced liver MDA content. Histopathological analysis of renal and hepatic tissues was in line with the biochemical results. In conclusion, DFX-loaded microemulsions induce less toxicity than free DFX and appear a more desirable and safer drug carrier in combating the iron-overload complications. Theoretical simulations are performed to get better insight regarding interactions between DFX and surfactant F127.


Assuntos
Deferasirox/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Sobrecarga de Ferro/tratamento farmacológico , Animais , Deferasirox/metabolismo , Emulsões/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Ferro/análise , Ferro/metabolismo , Ferro/toxicidade , Quelantes de Ferro/farmacologia , Sobrecarga de Ferro/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Micelas , Ratos , Ratos Wistar
2.
Ecotoxicol Environ Saf ; 203: 111054, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888616

RESUMO

Quinclorac (3,7-dichloroquinoline-8-carboxylic acid, QNC) is a highly selective auxin herbicide that is typically applied to paddy rice fields. Its residue is a serious problem in crop rotations. In this study, Oryza sativa L. seedlings was used as a model plant to explore its biochemical response to abiotic stress caused by QNC and nZVI coexposure, as well as the interactions between QNC and nZVI treatments. Exposure to 5 and 10 mg/L QNC reduced the fresh biomass by 26.6% and 33.9%, respectively, compared to the control. The presence of 50 and 250 mg/L nZVI alleviated the QNC toxicity, but the nZVI toxicity was aggravated by the coexist of QNC. Root length was enhanced upon exposure to low or medium doses of both QNC and nZVI, whereas root length was inhibited under high-dose coexposure. Both nZVI and QNC, either alone or in combination, significantly inhibited the biosynthesis of chlorophyll, and the inhibition rate increased with elevated nZVI and QNC concentration. It was indicated that nZVI or QNC can affect the plant photosynthesis, and there was a significant interaction between the two treatments. Effects of QNC on the antioxidant response of Oryza sativa L. differed in the shoots and roots; generally, the introduction of 50 and 250 mg/L nZVI alleviated the oxidative stress (POD in shoots, SOD and MDA in roots) induced by QNC. However, 750 mg/kg nZVI seriously damaged Oryza sativa L. seedlings, which likely resulted from active iron deficiency. QNC could be removed from the culture solution by nZVI; as a result, nZVI suppressed QNC uptake by 20%-30%.


Assuntos
Antioxidantes/metabolismo , Ferro/toxicidade , Nanopartículas/toxicidade , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quinolinas/toxicidade , Poluentes do Solo/toxicidade , Transporte Biológico , Biomassa , Clorofila/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo
3.
Ecotoxicol Environ Saf ; 205: 111337, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979804

RESUMO

Iron overload in water is a problem in many areas of the world, which could exert toxic effects on fish. To achieve maximum growth and overall fitness, iron induced toxicity must be alleviated. Therefore, this research was undertaken to investigate the potential mitigation of iron toxicity by dietary vitamin C supplementation in channel catfish (Ictalurus punctatus). Two doses of vitamin C (143 and 573 mg/kg diet) were tested against high environmental iron (HEI, 9.5 mg/L representing 25% of 96 h LC50). Fish were randomly divided into six groups with four replicated tanks. The groups were Control (vitamin C deficient feed), LVc (143 mg vitamin C supplemented per kg diet), HVc (573 mg vitamin C supplemented per kg diet), Con + Fe (control exposed to HEI), LVc + Fe (LVc exposed to HEI) and HVc + Fe (HVc exposed to HEI). Following an 8 week trial, there was a significant reduction in weight gain (WG%) in Con + Fe compared to the control, indicating a toxic effect of HEI on fish growth performance. Interestingly, WG% in both LVc + Fe and HVc + Fe groups were significantly higher than Cont + Fe, signifying that HEI inhibited growth, but this was alleviated by vitamin C. Both hemoglobin content and hematocrit were higher in LVc + Fe compared to the control and Con + Fe. In addition, exposure to HEI (Con + Fe) incited hepatic oxidative stress based on an over-accumulation of malondialdehyde (MDA) along with a significant inhibition in superoxide dismutase (SOD) and catalase (CAT) activities; whereas in LVc + Fe and HVc + Fe, the MDA content restored to basal level. A series of histopathological alterations were observed in the liver and gills, with the most severe lesions in Con + Fe, which was also complemented with a remarkable increase in hepatic iron accumulation. Vitamin C supplementations reduced the augmented concentrations of iron accumulation to that of the control. No effect, regardless of the treatments, was noted for fatty acid composition of muscle. Overall, our findings suggest that the vitamin C supplementation can be an effective therapeutic approach for boosting growth as well as alleviating iron toxicity in catfish.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Ictaluridae/metabolismo , Ferro/toxicidade , Poluentes Químicos da Água/toxicidade , Ração Animal , Animais , Antioxidantes/metabolismo , Dieta , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Ferro/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Poluentes Químicos da Água/metabolismo
4.
Chemosphere ; 254: 126844, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957274

RESUMO

The study aimed to evaluate the impact of iron (Fe) on the physiological and behavioural reaction of Chara tomentosa L. Fe was introduced into the environment in the form of iron chloride, the most common coagulants used in the restoration of water bodies. The investigations concerned the oxidative stress comprising phenolic compounds content, antioxidant activity and photosynthetic pigments concentration. Research was conducted as a laboratory microcosm experiment with one-off application of Fe at the level of 26.8 mg dm-3. Coagulant application caused short-term acidification, increased salinity and deterioration of light conditions. The shading resulted initially from the increase of water colour and turbidity and was followed by covering of the charophytes with a precipitated suspension. C. tomentosa did not activate defensive mechanisms to prevent the shading effect such as intensive elongation and elevated concentration of chlorophylls. Neither oxidative stress nor production of stress-specific phenolic metabolites was found. It was a result of iron coagulant toxicity, which led to cell membrane damage and leakage of cell contents to the water environment. Charophyte growth was significantly impaired, and thalli suffered numerous chlorotic and necrotic spots which extended gradually during experiment and finally caused death of specimens.


Assuntos
Carofíceas/efeitos dos fármacos , Ecossistema , Ferro/farmacologia , Fosfatos/farmacologia , Chara/efeitos dos fármacos , Carofíceas/crescimento & desenvolvimento , Precipitação Química , Clorofila/metabolismo , Ferro/toxicidade , Lagos/química , Estresse Oxidativo , Fenóis/análise , Água/química
5.
Appl Environ Microbiol ; 86(21)2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32859594

RESUMO

Iron is a highly reactive metal that participates in several processes in prokaryotic and eukaryotic cells. Hosts and pathogens compete for iron in the context of infection. Chromobacterium violaceum, an environmental Gram-negative bacterial pathogen, relies on siderophores to overcome iron limitation in the host. In this work, we studied the role of the ferric uptake regulator Fur in the physiology and virulence of C. violaceum A Δfur mutant strain showed decreased growth and fitness under regular in vitro growth conditions and presented high sensitivity to iron and oxidative stresses. Furthermore, the absence of fur caused derepression of siderophore production and reduction in swimming motility and biofilm formation. Consistent with these results, the C. violaceum Δfur mutant was highly attenuated for virulence and liver colonization in mice. In contrast, a manganese-selected spontaneous fur mutant showed only siderophore overproduction and sensitivity to oxidative stress, indicating that Fur remained partially functional in this strain. We found that mutations in genes related to siderophore biosynthesis and a putative CRISPR-Cas locus rescued the Δfur mutant growth defects, indicating that multiple Fur-regulated processes contribute to maintaining bacterial cell fitness. Overall, our data indicated that Fur is conditionally essential in C. violaceum mainly by protecting cells from iron overload and oxidative damage. The requirement of Fur for virulence highlights the importance of iron in the pathogenesis of C. violaceum IMPORTANCE Maintenance of iron homeostasis, i.e., avoiding both deficiency and toxicity of this metal, is vital to bacteria and their hosts. Iron sequestration by host proteins is a crucial strategy to combat bacterial infections. In bacteria, the ferric uptake regulator Fur coordinates the expression of several iron-related genes. Sometimes, Fur can also regulate several other processes. In this work, we performed an in-depth phenotypic characterization of fur mutants in the human opportunistic pathogen Chromobacterium violaceum We determined that fur is a conditionally essential gene necessary for proper growth under regular conditions and is fully required for survival under iron and oxidative stresses. Fur also controlled several virulence-associated traits, such as swimming motility, biofilm formation, and siderophore production. Consistent with these results, a C. violaceum fur null mutant showed attenuation of virulence. Therefore, our data established Fur as a major player required for C. violaceum to manage iron, including during infection in the host.


Assuntos
Proteínas de Bactérias/genética , Chromobacterium/fisiologia , Chromobacterium/patogenicidade , Ferro/toxicidade , Estresse Oxidativo , Proteínas Repressoras/genética , Sideróforos/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas Repressoras/metabolismo , Virulência
6.
Cancer Sci ; 111(6): 2016-2027, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32248600

RESUMO

Malignant mesothelioma (MM) is one of the most lethal tumors in humans. The onset of MM is linked to exposure to asbestos, which generates reactive oxygen species (ROS). ROS are believed to be derived from the frustrated phagocytosis and the iron in asbestos. To explore the pathogenesis of MM, peritoneal MM was induced in rats by the repeated intraperitoneal injection of iron saccharate and nitrilotriacetate. In the present study, we used microarray techniques to screen the microRNA (miR) expression profiles of these MM. We observed that the histological subtype impacted the hierarchical clustering of miR expression profiles and determined that miR-199/214 is a distinctive feature of iron saccharate-induced sarcomatoid mesothelioma (SM). Twist1, a transcriptional regulator of the epithelial-mesenchymal transition, has been shown to activate miR-199/214 transcription; thus, the expression level of Twist1 was examined in iron-induced and asbestos-induced mesotheliomas in rats. Twist1 was exclusively expressed in iron saccharate-induced SM but not in the epithelioid subtype. The Twist1-miR-199/214 axis is activated in iron saccharate-induced and asbestos-induced SM. The expression levels of miR-214 and Twist1 were correlated in an asbestos-induced MM cell line, suggesting that the Twist1-miR-199/214 axis is preserved. MeT5A, an immortalized human mesothelial cell line, was used for the functional analysis of miR. The overexpression of miR-199/214 promoted cellular proliferation, mobility and phosphorylation of Akt and ERK in MeT5A cells. These results indicate that miR-199/214 may affect the aggressive biological behavior of SM.


Assuntos
Neoplasias Pulmonares/patologia , Mesotelioma/patologia , MicroRNAs/biossíntese , Neoplasias Peritoneais/patologia , Proteína 1 Relacionada a Twist/biossíntese , Animais , Asbestos/toxicidade , Linhagem Celular , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Ferro/toxicidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mesotelioma/genética , Mesotelioma/metabolismo , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Ratos
7.
Sci Rep ; 10(1): 5206, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251356

RESUMO

Groundwater through hand-operated tubewell (a type of water well) tapping is the main source of drinking water in Bangladesh. This study investigated iron and manganese concentration in groundwater across Jashore district-one of the worst arsenic contaminated area in Bangladesh. One working tubewell that had been tested previously for arsenic and marked safe (green) was selected from each unions of the district. Results revealed that approximately 73% and 87% of groundwater samples exceeded the limits for iron and manganese in Bangladesh drinking water, respectively. Additionally, spatial distribution of iron and manganese indicate that only 5% of the total surface area of groundwater is covered by safe level of iron and manganese. Human health risk due to ingestion of iron and manganese through drinking water was evaluated using hazard quotients (HQ) for adults and children. The result of the health risk assessment revealed that the non-carcinogenic health risks due to ingestion of iron (HQ up to 1.446 for adults and 0.590 for children) and manganese (HQ up to 2.459 for adults and 1.004 for children) contaminated groundwater are much higher among adults than children. On the basis of occurrences, spatial distribution and health risk assessment results, the area can be categorized as a high-risk zone for iron and manganese-related problems and needs special attention in order to protect public health of local residents.


Assuntos
Água Subterrânea/química , Ferro/toxicidade , Manganês/toxicidade , Medição de Risco , Abastecimento de Água , Poços de Água , Adulto , Arsênico/análise , Bangladesh , Criança , Humanos , Ferro/análise , Manganês/análise
8.
BMC Bioinformatics ; 21(1): 118, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32192433

RESUMO

BACKGROUND: mRNA interaction with other mRNAs and other signaling molecules determine different biological pathways and functions. Gene co-expression network analysis methods have been widely used to identify correlation patterns between genes in various biological contexts (e.g., cancer, mouse genetics, yeast genetics). A challenge remains to identify an optimal partition of the networks where the individual modules (clusters) are neither too small to make any general inferences, nor too large to be biologically interpretable. Clustering thresholds for identification of modules are not systematically determined and depend on user-settable parameters requiring optimization. The absence of systematic threshold determination may result in suboptimal module identification and a large number of unassigned features. RESULTS: In this study, we propose a new pipeline to perform gene co-expression network analysis. The proposed pipeline employs WGCNA, a software widely used to perform different aspects of gene co-expression network analysis, and Modularity Maximization algorithm, to analyze novel RNA-Seq data to understand the effects of low-dose 56Fe ion irradiation on the formation of hepatocellular carcinoma in mice. The network results, along with experimental validation, show that using WGCNA combined with Modularity Maximization, provides a more biologically interpretable network in our dataset, than that obtainable using WGCNA alone. The proposed pipeline showed better performance than the existing clustering algorithm in WGCNA, and identified a module that was biologically validated by a mitochondrial complex I assay. CONCLUSIONS: We present a pipeline that can reduce the problem of parameter selection that occurs with the existing algorithm in WGCNA, for applicable RNA-Seq datasets. This may assist in the future discovery of novel mRNA interactions, and elucidation of their potential downstream molecular effects.


Assuntos
Ferro/química , Fígado/metabolismo , Software , Algoritmos , Animais , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Íons/química , Ferro/toxicidade , Fígado/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , RNA-Seq
9.
Chemosphere ; 251: 126432, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32169709

RESUMO

Environmental applications and potential risks of iron-based materials have attracted increasing attention. However, most previous studies focused on a single material. Comparative research using different iron-based materials under the same experimental conditions is still lacking. Here, six iron-based materials, including micro-sized and nanoscale Fe3O4 (i.e., mFe3O4 and nFe3O4), bulk and bare nanoscale zero-valent iron (i.e., mZVI and B-nZVI), starch-supported nZVI (S-nZVI), and activated carbon-supported nZVI (A-nZVI), were studied to compare their phytotoxicity in mung bean grown in suspensions with doses of 0, 300, 600 and 1000 mg/L. Taking the four toxicology parameters (seed germination rate, germination index, seedling elongation and biomass) together, the iron-based materials except mFe3O4 generally produced no significant phytotoxicity to mung bean even at 1000 mg/L. nFe3O4 and B-nZVI showed no higher phytotoxicity than their micro-sized counterparts (mFe3O4 and mZVI). All the materials resulted in increased Fe concentrations in seedlings particularly in roots, and mZVI and B-nZVI produced more significant effects. However, the Fe in the roots was difficultly translocated to the shoots. Compared to B-nZVI, nFe3O4 had lower bioavailability and bioaccumulation potential. XRD results confirmed that most Fe3O4 and B-nZVI remained unchanged during seedling growth, while support materials accelerated the corrosion and transformation of S-nZVI and A-nZVI. In conclusion, the tested nanoscale iron-based materials generally possess no obvious phytotoxicity within the dose range, but cause excess Fe accumulation in seedlings. Introduction of support materials may reduce such risk, allowing safer applications of these iron-based materials.


Assuntos
Germinação/efeitos dos fármacos , Ferro/toxicidade , Poluentes do Solo/toxicidade , Vigna/fisiologia , Carvão Vegetal/farmacologia , Nanopartículas Metálicas/toxicidade , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Sementes
10.
J Toxicol Environ Health B Crit Rev ; 23(3): 107-136, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32106786

RESUMO

Ambient air pollution is a leading risk factor for the global burden of disease. One possible pathway of particulate matter (PM)-induced toxicity is through iron (Fe), the most abundant metal in the atmosphere. The aim of the review was to consider the complexity of Fe-mediated toxicity following inhalation exposure focusing on the chemical and surface reactivity of Fe as a transition metal and possible pathways of toxicity via reactive oxygen species (ROS) generation as well as considerations of size, morphology, and source of PM. A broad term search of 4 databases identified 2189 journal articles and reports examining exposure to Fe via inhalation in the past 10 years. These were sequentially analyzed by title, abstract and full-text to identify 87 articles publishing results on the toxicity of Fe-containing PM by inhalation or instillation to the respiratory system. The remaining 87 papers were examined to summarize research dealing with in vitro, in vivo and epidemiological studies involving PM containing Fe or iron oxide following inhalation or instillation. The major findings from these investigations are summarized and tabulated. Epidemiological studies showed that exposure to Fe oxide is correlated with an increased incidence of cancer, cardiovascular diseases, and several respiratory diseases. Iron PM was found to induce inflammatory effects in vitro and in vivo and to translocate to remote locations including the brain following inhalation. A potential pathway for the PM-containing Fe-mediated toxicity by inhalation is via the generation of ROS which leads to lipid peroxidation and DNA and protein oxidation. Our recommendations include an expansion of epidemiological, in vivo and in vitro studies, integrating research improvements outlined in this review, such as the method of particle preparation, cell line type, and animal model, to enhance our understanding of the complex biological interactions of these particles.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição por Inalação/efeitos adversos , Ferro/toxicidade , Material Particulado/toxicidade , Animais , Humanos , Espécies Reativas de Oxigênio
11.
Biochem J ; 477(6): 1109-1122, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32108853

RESUMO

The toxicity of accumulated α-synuclein plays a key role in the neurodegeneration of Parkinson's disease (PD). This study has demonstrated that iron in varying concentrations (up to 400 µM) causes an increase in α-synuclein content in SH-SY5Y cells associated with mitochondrial depolarization, decreased cellular ATP content and loss of cell viability during incubation up to 96 h. Knocking-down α-synuclein expression prevents cytotoxic actions of iron, which can also be prevented by cyclosporine A (a blocker of mitochondrial permeability transition pore). These results indicate that iron cytotoxicity is mediated by α-synuclein acting on mitochondria. Likewise siRNA mediated knock-down of Parkin causes an accumulation of α-synuclein accompanied by mitochondrial dysfunction and cell death during 48 h incubation under basal conditions, but these changes are not further aggravated by co-incubation with iron (400 µM). We have also analyzed mitochondrial dysfunction and cell viability in SH-SY5Y cells under double knock-down (α-synuclein and Parkin concurrently) conditions during incubation for 48 h with or without iron. Our results tend to suggest that iron inactivates Parkin in SH-SY5Y cells and thereby inhibits the proteasomal degradation of α-synuclein, and the accumulated α-synuclein causes mitochondrial dysfunction and cell death. These results have implications in the pathogenesis of sporadic PD and also familial type with Parkin mutations.


Assuntos
Ferro/toxicidade , Doença de Parkinson/metabolismo , Domínios e Motivos de Interação entre Proteínas/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , alfa-Sinucleína/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos
12.
Chemosphere ; 247: 125895, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31958649

RESUMO

Humic acid plays an important role in controlling the toxicity of nanoparticles to organisms. However, little is known about the influence of different fractions of dissolved humic acid (DHA) from soil on the toxicity of nanoparticles to organisms. The concentration of γ-Fe2O3 and the exposure time affected the malondialdehyde (MDA) content, reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) activity in P. chrysosporium cells and were inversely proportional to the relative activities of the cells. P. chrysosporium was exposed to γ-Fe2O3 and DHA1 for 3 h, 6 h and 12 h. Catalase (CAT) and peroxidase (POD) activities were generally higher than control. Particularly, under the influence of 50 mg/L DHA1 and different concentrations of γ-Fe2O3 (10 and 50 mg/L), the CAT and POD activities were higher than those of cells exposed to γ-Fe2O3 alone. Conversely, both activities of P. chrysosporium exposed to DHA4 combined with γ-Fe2O3 for 12 h were lower than those of cells exposed to γ-Fe2O3 alone and gradually decreased with increasing DHA4 concentration (0, 10 and 50 mg/L). The µ-XAFS normalized spectrum indicated that Fe3+ entering the cells tended to transform into Fe2+ as the stress time prolonged. TEM analysis confirmed the toxicity of high concentrations of γ-Fe2O3 to P. chrysosporium. The comet assay showed that DHA4 in soil enhanced the toxicity of γ-Fe2O3 to P. chrysosporium more than DHA1 did. Namely, compared to DHA1, DHA4 made it easier for nano-Fe2O3 to enter P. chrysosporium cells, causing more toxicity of γ-Fe2O3 to P. chrysosporium.


Assuntos
Fungos/efeitos dos fármacos , Substâncias Húmicas/análise , Ferro/toxicidade , Nanopartículas/toxicidade , Catalase , Compostos Férricos/análise , Ferro/análise , Malondialdeído , Solo
13.
PLoS One ; 15(1): e0223086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31899771

RESUMO

Rice wild relatives (RWR) constitute an extended gene pool that can be tapped for the breeding of novel rice varieties adapted to abiotic stresses such as iron (Fe) toxicity. Therefore, we screened 75 Oryza genotypes including 16 domesticated O. sativa genotypes, one O. glaberrima, and 58 RWR representing 21 species, for tolerance to Fe toxicity. Plants were grown in a semi-artificial greenhouse setup, in which they were exposed either to control conditions, an Fe shock during the vegetative growth stage (acute treatment), or to a continuous moderately high Fe level (chronic treatment). In both stress treatments, foliar Fe concentrations were characteristic of Fe toxicity, and plants developed foliar stress symptoms, which were more pronounced in the chronic Fe stress especially toward the end of the growing season. Among the genotypes that produced seeds, only the chronic stress treatment significantly reduced yields due to increases in spikelet sterility. Moreover, a moderate but non-significant increase in grain Fe concentrations, and a significant increase in grain Zn concentrations were seen in chronic stress. Both domesticated rice and RWR exhibited substantial genotypic variation in their responses to Fe toxicity. Although no RWR strikingly outperformed domesticated rice in Fe toxic conditions, some genotypes scored highly in individual traits. Two O. meridionalis accessions were best in avoiding foliar symptom formation in acute Fe stress, while an O. rufipogon accession produced the highest grain yields in both chronic and acute Fe stress. In conclusion, this study provides the basis for using interspecific crosses for adapting rice to Fe toxicity.


Assuntos
Resistência à Doença/genética , Ferro/toxicidade , Oryza/genética , Doenças das Plantas/genética , Animais , Grão Comestível/efeitos dos fármacos , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Etanol , Genótipo , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Sementes/genética , Sementes/crescimento & desenvolvimento , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética
14.
Plant Physiol Biochem ; 147: 191-204, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865165

RESUMO

Cd, Cu, and Fe were used to reveal the specificity of their toxic actions. We studied the effects of heavy metals on the growth of barley seedlings, contents of cations in leaves and chloroplasts, induced chlorophyll fluorescence and P700 light absorption. Differences were found at each level of research. We measured the contents of Cd, Cu, Fe, Mn, Zn, Ca, Mg, and K. The proportion of cations in leaves targeted to chloroplasts varied from 0.1% (K) to >90% (Fe). Their levels changed in different ways. We found no correlation between changes in cation contents in leaves and chloroplasts. Treatment with Cd, Cu, and Fe increased the contents of some cations. The extra portions were targeted primarily out of chloroplasts, which was most noticeable in the case of Cu and Fe. Cd treatment decreased non-photochemical quenching with concomitant increases in closed photosystem II. We introduced new coefficients qC for closed photosystem II and X(II) to compare the yields of photosystem II and photosystem I. Cd likely decreased both PSI content in leaves and its quantum yield. In control plants, the quantum yield ratio of PSI/PSII increased gradually from 1.25 under low light to 4 under high light. Cd treatment prevented the increase under moderate light; under high light the ratio reached 2. Cu treatment increased the acceptor side limitation of photosystem I under low light; components of the Calvin cycle likely demand more light for activation in Cu-treated plants.


Assuntos
Hordeum , Metais Pesados , Complexo de Proteína do Fotossistema I , Complexo de Proteína do Fotossistema II , Cádmio/metabolismo , Cádmio/toxicidade , Clorofila/metabolismo , Cloroplastos/efeitos dos fármacos , Cobre/metabolismo , Cobre/toxicidade , Hordeum/química , Hordeum/efeitos dos fármacos , Ferro/metabolismo , Ferro/toxicidade , Luz , Metais Pesados/metabolismo , Metais Pesados/toxicidade , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema I/efeitos dos fármacos , Complexo de Proteína do Fotossistema II/efeitos dos fármacos , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos
15.
Nanotoxicology ; 14(2): 196-213, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31718350

RESUMO

Iron nanoparticles (NPs) have been proposed as a tool in very different fields such as environmental remediation and biomedical applications, including food fortification against iron deficiency, even if there is still concern about their safety. Here, we propose Xenopus laevis embryos as a suitable model to investigate the toxicity and the bio-interactions at the intestinal barrier of Fe3O4 and zerovalent iron (ZVI) NPs compared to Fe(II) and (III) salts in the 5 to 100 mg Fe/L concentration range using the Frog Embryo Teratogenesis Assay in Xenopus (FETAX). Our results demonstrated that, at concentrations at which iron salts induce adverse effects, both iron NPs do not cause acute toxicity or teratogenicity even if they accumulate massively in the embryo gut. Prussian blue staining, confocal and electron microscopy allowed mapping of iron NPs in enterocytes, along the paracellular spaces and at the level of the basement membrane of a well-preserved intestinal epithelium. Furthermore, the high bioaccumulation factor and the increase in embryo length after exposure to iron NPs suggest greater iron intake, an essential element for organisms. Together, these results improve the knowledge on the safety of orally ingested iron NPs and their interaction with the intestinal barrier, useful for defining the potential risks associated with their use in food/feed fortification.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Óxido Ferroso-Férrico/toxicidade , Ferro/toxicidade , Nanopartículas Metálicas/toxicidade , Teratogênese/efeitos dos fármacos , Teratogênios/toxicidade , Animais , Bioensaio , Desenvolvimento Embrionário/efeitos dos fármacos , Óxido Ferroso-Férrico/química , Ferro/química , Nanopartículas Metálicas/química , Testes de Toxicidade/métodos , Xenopus laevis
16.
Biochim Biophys Acta Mol Cell Res ; 1867(2): 118621, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31812496

RESUMO

BACKGROUND: Increased body iron stores have been implicated in the pathogenesis of diabetes mellitus. However, the molecular mechanisms involved are unclear. The liver plays a central role in homeostasis of iron and glucose in the body. Mice deficient in hepcidin (the central regulator of systemic iron homeostasis) (Hamp1-/- mice) accumulate iron in the liver in vivo. The effects of such iron loading on hepatic insulin signaling and glucose metabolism are not known. METHODS: Hepatocytes isolated from Hamp1-/- mice were studied for markers of insulin signaling (and its downstream effects), glucose production, expression of gluconeogenic and lipogenic enzymes, and markers of AMPK (AMP-activated protein kinase) activation and oxidative stress. These parameters were studied both in the absence and presence of insulin, and also with the use of an iron chelator. RESULTS: Akt in the insulin signaling pathway was found to be activated in the Hamp1-/- hepatocytes to a greater extent than wild-type (WT) cells, both under basal conditions and in response to insulin. Incubation of the Hamp1-/- hepatocytes with an iron chelator attenuated these effects. There was no evidence of oxidative stress or AMPK activation in the Hamp1-/- hepatocytes. Glucose production by these cells was similar to that by WT cells. Gene expression of key gluconeogenic enzymes was decreased in these cells. In addition, they showed evidence of increased lipogenesis. CONCLUSIONS: Hepatocytes from Hamp1-/- mice showed evidence of greater sensitivity to the effects of insulin than WT hepatocytes. This may explain the insulin-sensitive phenotype that has been reported in classical hemochromatosis.


Assuntos
Hepcidinas/genética , Insulina/metabolismo , Ferro/toxicidade , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células Cultivadas , Ferritinas/metabolismo , Glucose/metabolismo , Glucose-6-Fosfatase/metabolismo , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepcidinas/deficiência , Insulina/farmacologia , Ferro/metabolismo , Quelantes de Ferro/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo
17.
Biomed Pharmacother ; 122: 109690, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786468

RESUMO

Excess iron content can build up in the retina and lead to iron-mediated retinal injury. An important isoflavone C-glucoside, puerarin, has been reported to be involved in retinal protection. In this experiment, we studied the effects and potential mechanisms of puerarin on retinal injury in vivo and in vitro. We found that puerarin reduced serum and retinal iron content, attenuated the pathophysiological changes and retinal iron deposition, and partially prevented the decrease of rhodopsin and retinal pigment epithelium-specific 65 kDa protein expression in retinas of iron-overload mice. Puerarin rescued the abnormal expression of iron-handling proteins in the mouse retina and suppressed the oxidative stress induced by iron overload, as evident from the enhanced activity of superoxide dismutase, catalase, and glutathione peroxidase and decreased content of malondialdehyde. Moreover, puerarin inhibited the phosphorylation of p38 and ERK mitogen-activated protein kinases (MAPKs) and signal transducer and activator of transcription 3 (STAT3), thereby protecting the retinal cells from apoptosis by suppressing cytochrome c release, caspase activation, and poly (ADP-ribose) polymerase cleavage in vivo. Also, the ability of puerarin to regulate iron-handling proteins, decrease intracellular Fe2+, and inhibit cell apoptosis was further confirmed in ARPE-19 cells. The experimental data verify the protective role of puerarin in the treatment of retinal injury caused by iron overload; its possible mechanisms might be associated with regulation of iron-handling proteins, enhancement of the antioxidant capacity, and the inhibition of MAPK and STAT3 activation and the apoptotic pathways under iron overload conditions.


Assuntos
Sobrecarga de Ferro , Isoflavonas/farmacologia , Retina/efeitos dos fármacos , Retina/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Canais de Cálcio Tipo L/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Ferro/sangue , Ferro/metabolismo , Ferro/toxicidade , Isoflavonas/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Retina/metabolismo , Doenças Retinianas/induzido quimicamente , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , cis-trans-Isomerases/metabolismo
18.
Ecotoxicol Environ Saf ; 189: 110008, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31796254

RESUMO

Excess iron (Fe) is commonly observed in wetland rice (Oryza sativa L.) plants, impairing crop growth and productivity. Some information suggests that silicon (Si) can reduce Fe content in leaves and roots of rice (vegetative phase), but nothing is known if Si could mitigate the effects of Fe toxicity on rice production and photosynthesis. Here, we assessed the role of Si in alleviating the well-known effects of Fe toxicity on nutritional imbalances, biomass accumulation, photosynthesis and grain yield using two rice cultivars having differential abilities to tolerate excess Fe. Plants were hydroponically grown under two Fe levels (25 µM or 5 mM) and the nutrient solutions were amended with Si (0 or 2 mM). Under excess Fe were detected (i) nutritional deficiencies, especially of calcium and magnesium in leaves; (ii) negligible changes in grain nutritional composition, independently of Si application; (iii) decreases in net photosynthetic rates, stomatal conductance and electron transport rate, in parallel to decreased grain yield components (total grain biomass, 1000-grain mass, percentage of filled grains, number of grains per plant and harvest index), especially in the Fe-sensitive cultivar. These impairments were partially reversed by the application of Si. Results also suggest that Si alleviated the negative impacts of Fe on spikelet sterility. In summary, we conclude that the use of Si can be recommended as an effective management strategy to reduce the negative impacts of Fe toxicity on rice photosynthetic performance and crop yield.


Assuntos
Grão Comestível/efeitos dos fármacos , Ferro/toxicidade , Oryza/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Silício/farmacologia , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Hidroponia , Ferro/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade
19.
Artigo em Inglês | MEDLINE | ID: mdl-31739468

RESUMO

The toxicity of arsenic (As) could be influenced by many environmental factors and elements. Iron (Fe) is one of the elements that could be involved in As-induced toxicity. In this study, the interactive effects of Fe and As in HepG2 cells were analyzed based on cytotoxicity and transcriptomic analyses. The results showed that Fe could decrease cell viability and increase mitochondrial depolarization induced by As exposure. Oxidative stress and damage have been proven to be one of the main mechanisms of As toxicity. Our results showed that Fe increased the generation of reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) induced by As exposure. Microarray analysis further verified that Fe increased the alteration of gene expression and biological processes related to oxidative stress, cell proliferation, and the apoptotic signaling pathway caused by As exposure. Both results of cytotoxicity and transcriptomic analyses suggest that an increase of Fe in the human body could increase the As-induced toxicity, which should be considered during the health risk assessment of As.


Assuntos
Arsênico/toxicidade , Ferro/toxicidade , Transcriptoma/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
20.
Life Sci ; 239: 116878, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31669736

RESUMO

AIMS: We previously demonstrated that iron-overload in non-thalassemic rats induced neurotoxicity and cognitive decline. However, the effect of iron-overload on the brain of thalassemic condition has never been investigated. An iron chelator (deferiprone) provides neuroprotective effects against metal toxicity. Furthermore, a T-type calcium channels blocker (efonidipine) effectively attenuates cardiac dysfunction in thalassemic mice with iron-overload. However, the effects of both drugs on brain of iron-overload thalassemia has not been determined. We hypothesize that iron-overload induces neurotoxicity in Thalassemic and wild-type mice, and not only deferiprone, but also efonidipine, provides neuroprotection against iron-overload condition. MAIN METHODS: Mice from both wild-type (WT) and ß-thalassemic type (HT) groups were assigned to be fed with a standard-diet or high-iron diet containing 0.2% ferrocene/kg of diet (HFe) for 4 months consecutively. After three months of HFe, 75-mg/kg/d deferiprone or 4-mg/kg/d efonidipine were administered to the HFe-fed WT and HT mice for 1 month. KEY FINDINGS: HFe consumption caused an equal impact on circulating iron-overload, oxidative stress, and inflammation in WT and HT mice. Brain iron-overload and iron-mediated neurotoxicity, such as oxidative stress, inflammation, glial activation, mitochondrial dysfunction, and Alzheimer's like pathologies, were observed to an equal degree in HFe fed WT and HT mice. These pathological conditions were mitigated by both deferiprone and efonidipine. SIGNIFICANCE: These findings indicate that iron-overload itself caused neurotoxicity, and T-type calcium channels may play a role in this condition.


Assuntos
Deferiprona/farmacologia , Di-Hidropiridinas/farmacologia , Ferro/toxicidade , Nitrofenóis/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/efeitos dos fármacos , Deferiprona/metabolismo , Di-Hidropiridinas/metabolismo , Modelos Animais de Doenças , Ferro/metabolismo , Quelantes de Ferro/farmacologia , Sobrecarga de Ferro/patologia , Camundongos , Camundongos Endogâmicos C57BL , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Nitrofenóis/metabolismo , Compostos Organofosforados/metabolismo , Compostos Organofosforados/farmacologia , Talassemia/patologia
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