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1.
Int J Mol Sci ; 23(6)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35328338

RESUMO

PURPOSE: The lack of suitable animal models for (dry) age-related macular degeneration (AMD) has hampered therapeutic research into the disease, so far. In this study, pigmented rats and mice were systematically injected with various doses of sodium iodate (SI). After injection, the retinal structure and visual function were non-invasively characterized over time to obtain in-depth data on the suitability of these models for studying experimental therapies for retinal degenerative diseases, such as dry AMD. METHODS: SI was injected into the tail vein (i.v.) using a series of doses (0-70 mg/kg) in adolescent C57BL/6J mice and Brown Norway rats. The retinal structure and function were assessed non-invasively at baseline (day 1) and at several time points (1-3, 5, and 10-weeks) post-injection by scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and electroretinography (ERG). RESULTS: After the SI injection, retinal degeneration in mice and rats yielded similar results. The lowest dose (10 mg/kg) resulted in non-detectable structural or functional effects. An injection with 20 mg/kg SI did not result in an evident retinal degeneration as judged from the OCT data. In contrast, the ERG responses were temporarily decreased but returned to baseline within two-weeks. Higher doses (30, 40, 50, and 70 mg/kg) resulted in moderate to severe structural RPE and retinal injury and decreased the ERG amplitudes, indicating visual impairment in both mice and rat strains. CONCLUSIONS: After the SI injections, we observed dose-dependent structural and functional pathological effects on the retinal pigment epithelium (RPE) and retina in the pigmented mouse and rat strains that were used in this study. Similar effects were observed in both species. In particular, a dose of 30 mg/kg seems to be suitable for future studies on developing experimental therapies. These relatively easily induced non-inherited models may serve as useful tools for evaluating novel therapies for RPE-related retinal degenerations, such as AMD.


Assuntos
Degeneração Macular , Degeneração Retiniana , Animais , Modelos Animais de Doenças , Eletrorretinografia , Seguimentos , Iodatos , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/tratamento farmacológico , Degeneração Macular/patologia , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Retina/patologia , Degeneração Retiniana/diagnóstico por imagem , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/patologia , Sódio/farmacologia , Tomografia de Coerência Óptica
2.
Oxid Med Cell Longev ; 2022: 1792894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251467

RESUMO

Excessive reactive oxygen species (ROS) contribute to damage of retinal cells and the development of retinal diseases including age-related macular degeneration (AMD). ROS result in increased metabolites of lipoxygenases (LOXs), which react with ROS to induce lipid peroxidation and may lead to ferroptosis. In this study, the effect of 5-LOX inhibition on alleviating ROS-induced cell death was evaluated using sodium iodate (NaIO3) in the retinal pigment epithelium (RPE) cell line ARPE-19 and a mouse model investigating oxidative stress in AMD. We demonstrated that NaIO3 induced cell death in the RPE cells through mechanisms including ferroptosis. Inhibition of 5-LOX with specific inhibitor, Zileuton, or siRNA knockdown of ALXO5 mitigated NaIO3-induced lipid peroxidation, mitochondrial damage, DNA impairment, and cell death in ARPE-19 cells. Additionally, in the mouse model, pretreatment with Zileuton reduced the NaIO3-induced lipid peroxidation of RPE cells, cell death in the photoreceptor layer of the retina, inflammatory responses, and degeneration of both the neuroretina and RPE monolayer cells. Our results suggest that 5-LOX plays a crucial role in ROS-induced cell death in the RPE and that regulating 5-LOX activity could be a useful approach to control ROS and ferroptosis-induced damage, which promote degeneration in retinal diseases.


Assuntos
Araquidonato 5-Lipoxigenase/metabolismo , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Iodatos/efeitos adversos , Degeneração Macular/induzido quimicamente , Degeneração Macular/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Animais , Araquidonato 5-Lipoxigenase/genética , Linhagem Celular , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes/métodos , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/análogos & derivados , Inibidores de Lipoxigenase/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Substâncias Protetoras/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos , Transfecção/métodos
3.
Anal Methods ; 14(7): 741-749, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35108716

RESUMO

This work presents the use of a 96-well plate as headspaces for the determination of ascorbic acid in samples loaded in the 96-well plate. Ascorbic acid in the sample is oxidized to iodide by the addition of excess acidic iodate solution into the well. The iodide is further oxidized by the remaining iodate to molecular iodine. A single sheet of moist starch indicator paper is immediately placed over the 96-well plate after the addition of the iodate with the moisture forming a gas seal. The iodine gas in each well diffuses through the headspace to react with the starch paper producing circular areas of a colored starch-iodine complex. After 15 min the indicator paper is scanned, and the digital images of the complex are analyzed by using ImageJ software to obtain blue intensity values. The precision of the intensity values from 12 wells containing 20 µL of 2.84 mM standard ascorbic acid is <2% relative standard deviation. Optimal conditions for detection were investigated, including the starch concentration, the acidic iodate reagent, and the measurement time. The linear calibration range of ascorbic acid is 0.284-2.84 mM, based on the plot of concentration vs. -log(reflectance). The coefficient of determination (r2) is >0.998. Samples of fruit juice and dietary supplements were analyzed for their ascorbic acid contents. The results obtained from the headspace reflectance method are not statistically different from values obtained from the titration method using paired t-tests (α = 0.05).


Assuntos
Iodatos , Iodo , Ácido Ascórbico , Iodetos , Amido
4.
Sci Total Environ ; 825: 153871, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35176370

RESUMO

The present study investigates the kinetics and mechanisms of carbamazepine (CBZ) degradation using a novel UV/iodate (IO3-) system for the first time and explores the influence of process conditions on its degradation. UV/IO3- showed high degradation efficiencies in a wide range of pHs, especially under neutral and acidic conditions, indicating that the system can be considered as a promising method to deal with effluents under various pH conditions. Radical scavenging experiments show that both iodine radicals (IO, IO2 and IO3) and hydroxyl radicals play an important role in CBZ degradation. Furthermore, the combination of UV/IO3- with TiO2 was studied to explore the potential of the addition of IO3- to improve the efficiency of the conventional TiO2 photocatalytic system. Scavenging experiments indicated that iodine radicals (IO, IO2 and IO3) were mainly involved in the degradation of CBZ in the UV/IO3-/TiO2 system, and the reaction mechanism equations were proposed for the first time for the studied UV/IO3-/TiO2 system. Several degradation products and four possible pathways of CBZ degradation were also elucidated using ultra-high-performance liquid chromatography in combination with a quadrupole time-of-flight mass spectrometer (Q-TOF MS). Respirometric tests indicated that the treatment has a positive impact on biomass behavior during subsequent biological purification, highlighting that the developed IO3--assisted AOPs are eco-friendly.


Assuntos
Iodo , Poluentes Químicos da Água , Carbamazepina/análise , Iodatos , Iodetos , Cinética , Titânio/química , Água , Poluentes Químicos da Água/análise
5.
ISME J ; 16(1): 38-49, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215855

RESUMO

Iodine is oxidized and reduced as part of a biogeochemical cycle that is especially pronounced in the oceans, where the element naturally concentrates. The use of oxidized iodine in the form of iodate (IO3-) as an electron acceptor by microorganisms is poorly understood. Here, we outline genetic, physiological, and ecological models for dissimilatory IO3- reduction to iodide (I-) by a novel estuarine bacterium, Denitromonas sp. IR-12. Our results show that dissimilatory iodate reduction (DIR) by strain IR-12 is molybdenum-dependent and requires an IO3- reductase (idrA) and likely other genes in a mobile cluster with a conserved association across known and predicted DIR microorganisms (DIRM). Based on genetic and physiological data, we propose a model where three molecules of IO3- are likely reduced to three molecules of hypoiodous acid (HIO), which rapidly disproportionate into one molecule of IO3- and two molecules of iodide (I-), in a respiratory pathway that provides an energy yield equivalent to that of nitrate or perchlorate respiration. Consistent with the ecological niche expected of such a metabolism, idrA is enriched in the metagenome sequence databases of marine sites with a specific biogeochemical signature (high concentrations of nitrate and phosphate) and diminished oxygen. Taken together, these data suggest that DIRM help explain the disequilibrium of the IO3-:I- concentration ratio above oxygen-minimum zones and support a widespread iodine redox cycle mediated by microbiology.


Assuntos
Bactérias , Iodatos , Bactérias/genética , Bactérias/metabolismo , Iodatos/metabolismo , Metagenoma , Oxirredução , Filogenia
6.
J Org Chem ; 87(1): 652-669, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34931829

RESUMO

A simple method for the synthesis of (E)-3-arylimino-3H-indolizin-4-ium-1-olates by an iodate-promoted multicomponent reaction between 3,3-difluorocyclopropenes, pyridines, and anilines was discovered. The reaction products belong to a limited and underexplored class of pseudo-cross-conjugated heterocyclic mesomeric betaines isoconjugated with odd nonalternant hydrocarbon anions, whose properties were studied. Reversible nucleophilic addition at the C5 position was revealed as their main chemical feature, which had an access to novel fully conjugated 1,5-dioxo-3-arylamino-1,5-dihydroindolizine and tetracyclic 4-oxo-4,6-dihydrocyclopenta[4,5]pyrimido[2,1,6-cd]indolizine ring systems in one step. Both the synthesis of betaines and their transformations demonstrate a high level of functional group compatibility, allowing the ready preparation of a number of structurally attractive compounds for materials or medicinal chemistry.


Assuntos
Betaína , Piridinas , Compostos de Anilina , Ânions , Iodatos
7.
Food Chem ; 368: 130810, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34403996

RESUMO

A novel method based on diffused reflectance Fourier-transform infrared spectroscopy (DRS-FTIR) was employed for iodate determination in food grade salt and food products. The method attained sensitivity that was comparable to or better than that in most of the contemporary spectrophotometric methods. This was realized through a combination of azo dye formation and dispersive liquid-liquid microextraction of dye when a 37-fold enrichment was obtained. FT-IR enabled integrating alternative target peak, and freedom in sample solvent composition relative to UV-visible spectrophotometry where the solvent polarity, pH, and presence of ions may affect the spectral properties of the measurable coloured species. Food samples containing iodide or covalently bonded iodine were oxidized with alkaline permanganate for mineralization and iodate formation. Optimization of both reaction conditions was carried out by means of response surface methodology. The method had a linear range 0.04-10 mg kg-1 iodate and limit of detection of 4.4 µg kg-1.


Assuntos
Microextração em Fase Líquida , Iodatos/análise , Iodetos/análise , Limite de Detecção , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Small Methods ; 5(12): e2100848, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34928015

RESUMO

Lethal oxidative stress and ferrous ion accumulation-mediated degeneration/death in retinal pigment epithelium (RPE) exert an indispensable impact on retinal degenerative diseases with irreversible visual impairment, especially in age-related macular degeneration (AMD), but corresponding pathogenesis-oriented medical intervention remains controversial. In this study, the potent iron-binding nanoscale Prussian blue analogue KCa[FeIII (CN)6 ] (CaPB) with high biocompatibility is designed to inhibit RPE death and subsequently photoreceptor cell degeneration. In mice, CaPB effectively prevents RPE degeneration and ultimately fulfills superior therapeutic outcomes upon a single intravitreal injection: significant rescue of retinal structures and visual function. Through high-throughput RNA sequencing and sophisticated biochemistry evaluations, the findings initially unveil that CaPB nanoparticles protect against RPE degradation by inhibiting ferroptotic cell fate. Together with the facile, large-scale preparations and in vivo biosafety, it is believed that the synthesized CaPB therapeutic nanoparticles are promising for future clinical treatment of diverse retinal diseases involving pathological iron-dependent ferroptosis, including AMD.


Assuntos
Ferrocianetos/administração & dosagem , Ferroptose/efeitos dos fármacos , Iodatos/efeitos adversos , Degeneração Macular/tratamento farmacológico , Epitélio Pigmentado da Retina/citologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Ferrocianetos/química , Ferrocianetos/farmacologia , Perfilação da Expressão Gênica , Humanos , Injeções Intravítreas , Degeneração Macular/induzido quimicamente , Degeneração Macular/genética , Masculino , Camundongos , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , RNA-Seq , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo
9.
Nutrients ; 13(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34959962

RESUMO

Age-related macular degeneration (AMD) is one of the major causes of blindness in elderly populations. However, the dry form of AMD has lack of effective treatments. The fruits of Aronia melanocarpa are rich in anthocyanins. In this study, the protective effects of aronia fruit extract on rat retina were investigated using a NaIO3-induced dry AMD model. Full-field electroretinograms (ERGs) showed that b-wave amplitudes were significantly decreased and the retina structures were disordered in the model. The extract treatment alleviated the injuries. The b-wave amplitudes increased 61.5% in Scotopic 0.01ERG, 122.0% in Photopic 3.0ERG, and 106.8% in Photopic 3.0 flicker; the retina structure disorder was improved with the thickness of outer nuclear layer increasing by 44.1%; and the malonaldehyde level was significantly reduced in extract-treated rat retinas compared to the model. The proteomics analysis showed the expressions of five crystallin proteins, α-crystallin A chain, ß-crystallin B2, ß-crystallin A3, α-crystallin B chain, and γ-crystallin S, which protect retina ganglion cells, were increased by 7.38-, 7.74-, 15.30-, 4.86-, and 9.14-fold, respectively, in the extract treatment compared to the control, which was also confirmed by immunoblotting. The results suggest that aronia fruit extract, probably due to its anthocyanins, could protect the rat retina by alleviating oxidative damages and by upregulating the crystallin proteins to protect its nerve system.


Assuntos
Antocianinas/farmacologia , Antocianinas/uso terapêutico , Frutas/química , Iodatos/efeitos adversos , Degeneração Macular/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Photinia/química , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Retina/efeitos dos fármacos , Animais , Antocianinas/isolamento & purificação , Modelos Animais de Doenças , Degeneração Macular/patologia , Masculino , Extratos Vegetais/isolamento & purificação , Ratos Sprague-Dawley , Retina/patologia
10.
Oxid Med Cell Longev ; 2021: 4053276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34840667

RESUMO

Dry age-related macular degeneration (dAMD) is a chronic degenerative ophthalmopathy that leads to serious burden of visual impairment. Antioxidation in retinal pigment epithelium (RPE) cells is considered as a potential treatment for dAMD. Our previous studies have showed that naringenin (NAR) protects RPE cells from oxidative damage partly through SIRT1-mediated antioxidation. In this study, we tested the hypothesis that the Nrf2 signaling is another protective mechanism of NAR on dAMD. NaIO3-induced mouse retinopathy and ARPE-19 cell injury models were established. Immunochemical staining, immunofluorescence, and western blotting were performed to detect the protein expressions of Nrf2 and HO-1. In addition, ML385 (activity inhibitor of Nrf2) and zinc protoporphyrin (ZnPP, activity inhibitor of HO-1) were applied to explore the effect of NaIO3 or NAR. The results showed that NAR increased the protein expressions of Nrf2 and HO-1 in the retinas in mice exposed to NaIO3 at the early stage. NAR treatment also resulted in a stronger activation of Nrf2 at the early stage in NaIO3-treated ARPE-19 cells. Moreover, inhibition of HO-1 by ZnPP weakened the cytoprotective effect of NAR. The constitutive accumulation and activation of Nrf2 induced by NaIO3 led to the death of RPE cells. However, NAR decreased the protein expressions of Nrf2 and HO-1 towards normal level in the mouse retinas and ARPE-19 cells exposed to NaIO3 at the late stage. Our findings indicate that NAR protects RPE cells from oxidative damage via activating the Nrf2 signaling pathway.


Assuntos
Flavanonas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Doenças Retinianas/tratamento farmacológico , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Antagonistas de Estrogênios/farmacologia , Feminino , Iodatos/toxicidade , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Regulação para Cima
11.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502128

RESUMO

Age-related macular degeneration (AMD), one of the leading causes of blindness worldwide, causes personal suffering and high socioeconomic costs. While there has been progress in the treatments for the neovascular form of AMD, no therapy is yet available for the more common dry form, also known as geographic atrophy. We analysed the retinal tissue in a mouse model of retinal degeneration caused by sodium iodate (NaIO3)-induced retinal pigment epithelium (RPE) atrophy to understand the underlying pathology. RNA sequencing (RNA-seq), qRT-PCR, Western blot, immunohistochemistry of the retinas and multiplex ELISA of the mouse serum were applied to find the pathways involved in the degeneration. NaIO3 caused patchy RPE loss and thinning of the photoreceptor layer. This was accompanied by the increased retinal expression of complement components c1s, c3, c4, cfb and cfh. C1s, C3, CFH and CFB were complement proteins, with enhanced deposition at day 3. C4 was upregulated in retinal degeneration at day 10. Consistently, the transcript levels of proinflammatory ccl-2, -3, -5, il-1ß, il-33 and tgf-ß were increased in the retinas of NaIO3 mice, but vegf-a mRNA was reduced. Macrophages, microglia and gliotic Müller cells could be a cellular source for local retinal inflammatory changes in the NaIO3 retina. Systemic complement and cytokines/chemokines remained unaltered in this model of NaIO3-dependent retinal degeneration. In conclusion, systemically administered NaIO3 promotes degenerative and inflammatory processes in the retina, which can mimic the hallmarks of geographic atrophy.


Assuntos
Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Suscetibilidade a Doenças , Iodatos/efeitos adversos , Degeneração Retiniana/etiologia , Degeneração Retiniana/metabolismo , Animais , Apoptose/genética , Apoptose/imunologia , Proteínas do Sistema Complemento/genética , Modelos Animais de Doenças , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata , Imuno-Histoquímica , Camundongos , Degeneração Retiniana/patologia
12.
Sensors (Basel) ; 21(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209984

RESUMO

Iodine is a trace chemical element fundamental for a healthy human organism. Iodine deficiency affects about 2 billion people worldwide causing from mild to severe neurological impairment, especially in children. Nevertheless, an adequate nutritional intake is considered the best approach to prevent such disorders. Iodine is present in seawater and seafood, and its common forms in the diet are iodide and iodate; most iodide in seawater is caused by the biological reduction of the thermodynamically stable iodate species. On this basis, a multisensor instrument which is able to perform a multidimensional assessment, evaluating iodide content in seawater and seafood (via an electrochemical sensor) and discriminating when the seafood is fresh or defrosted quality (via a Quartz Micro balance (QMB)-based volatile and gas sensor), is strategic for seafood quality assurance. Moreover, an electronic interface has been opportunely designed and simulated for a low-power portable release of the device, which should be able to identify seafood over or under an iodide threshold previously selected. The electrochemical sensor has been successfully calibrated in the range 10-640 µg/L, obtaining a root mean square error in cross validation (RMSECV) of only 1.6 µg/L. Fresh and defrosted samples of cod, sea bream and blue whiting fish have been correctly discriminated. This proof-of-concept work has demonstrated the feasibility of the proposed application which must be replicated in a real scenario.


Assuntos
Iodetos , Iodo , Animais , Criança , Humanos , Iodatos , Alimentos Marinhos/análise , Água do Mar
13.
Exp Eye Res ; 210: 108700, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245755

RESUMO

Age-related macular degeneration (AMD) is a complex retinal disease with no viable treatment strategy. The causative mechanistic pathway for this disease is not yet clear. Therefore, it is highly warranted to screen effective drugs to treat AMD. Rapamycin are known to inhibit inflammation and has been widely used in the clinic as an immunosuppressant. This study aimed to investigate the protective effect of rapamycin on the AMD retinal degeneration model. The AMD models were established by injection of 35 mg/kg sodium iodate (NaIO3) into the tail vein. Then the treated mice intraperitoneally received rapamycin (2 mg/kg) once a day. The histomorphological analysis showed that rapamycin could inhibit retinal structure damage and apoptosis. Experiments revealed that rapamycin significantly attenuated inflammatory response and oxidative stress. Our experimental results demonstrated that rapamycin has protected the retinal against degeneration induced by NaIO3. The therapeutic effect was more significant after 7 days of treatment. Therefore, our study potentially provides a powerful experimental support for the treatment of AMD.


Assuntos
Modelos Animais de Doenças , Imunossupressores/uso terapêutico , Degeneração Retiniana/prevenção & controle , Epitélio Pigmentado da Retina/efeitos dos fármacos , Sirolimo/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Marcação In Situ das Extremidades Cortadas , Injeções Intraperitoneais , Iodatos/toxicidade , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Retina/metabolismo , Retina/patologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Rodopsina/metabolismo , cis-trans-Isomerases/metabolismo
14.
Transl Vis Sci Technol ; 10(8): 10, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34251426

RESUMO

Purpose: We aimed to explore differences in the NaIO3-elicited responses of retinal pigment epithelium (RPE) and other retinal cells associated with mouse strains and dosing regimens. Methods: One dose of NaIO3 at 10 or 15 mg/kg was given intravenously to adult male C57BL/6J and 129/SV-E mice. Control animals were injected with PBS. Morphologic and functional changes were characterized by spectral domain optical coherence tomography, electroretinography, histologic, and immunofluorescence techniques. Results: Injection with 10 mg/kg of NaIO3 did not cause consistent RPE or retinal changes in either strain. Administration of 15 mg/kg of NaIO3 initially induced a large transient increase in scotopic electroretinography a-, b-, and c-wave amplitudes within 12 hours of injection, followed by progressive structural and functional degradation at 3 days after injection in C57BL/6J mice and at 1 week after injection in 129/SV-E mice. RPE cell loss occurred in a large posterior-central lesion with a ring-like transition zone of abnormally shaped cells starting 12 hours after NaIO3 treatment. Conclusions: NaIO3 effects depended on the timing, dosage, and mouse strain. The RPE in the periphery was spared from damage compared with the central RPE. The large transient increase in the electroretinography was remarkable. Translational Relevance: This study is a phase T1 translational research study focusing on the development and validation of a mouse model of RPE damage. It provides a detailed foundation for future research, informing choices of mouse strain, dosage, and time points to establish NaIO3-induced RPE damage.


Assuntos
Iodatos , Epitélio Pigmentado da Retina , Animais , Eletrorretinografia , Iodatos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Food Chem ; 358: 129857, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33940293

RESUMO

In this study, a sensitive, selective, and environmentally friendly analytical method for direct extraction and preconcentration of iodine was developed. Iodine, as an iodate ion or iodide ion, was simultaneously extracted and preconcentrated by gel electromembrane microextraction (G-EME) and analyzed for total iodine by ion chromatography. The total iodine was determined by combining the peak areas of both iodate and iodide ions. Under the optimized conditions, linear calibration for iodine using a mixture of iodate and iodide ions was obtained from 10 to 100 µg L-1 (r2 > 0.996). The detection limit was 7.0 µg L-1. Recoveries of spiked iodine (as iodate) in the samples were greater than 90%. The method was applied for the determination of iodine in dietary supplements and fortified food samples, i.e., iodine-enriched eggs. Our developed method could be directly applied for the determination of iodine in different matrix samples including eggs without a pretreatment step.


Assuntos
Cromatografia/métodos , Suplementos Nutricionais/análise , Análise de Alimentos/métodos , Alimentos Fortificados/análise , Iodo/análise , Calibragem , Cromatografia/instrumentação , Análise de Alimentos/instrumentação , Química Verde/métodos , Iodatos/análise , Iodatos/isolamento & purificação , Iodetos/química , Limite de Detecção , Microextração em Fase Líquida/instrumentação , Microextração em Fase Líquida/métodos , Membranas Artificiais
16.
Oxid Med Cell Longev ; 2021: 6691402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854697

RESUMO

The retinal pigment epithelium (RPE) performs many functions that maintain photoreceptor health. Oxidative damage to the RPE is a critical component in the pathogenesis of eye diseases such as age-related macular degeneration (AMD). Ligands of the cluster of differentiation 36 (CD36) have previously preserved photoreceptor integrity in mouse models of AMD. The cytoprotective effect of the CD36 ligand MPE-001 on RPE cells has now been elucidated employing a model of oxidative stress. Sodium iodate (NaIO3) induced formation of reactive oxygen species and apoptosis in human RPE cells, which were decreased by MPE-001 without affecting antioxidant enzyme transcription. Immunoblotting and immunostaining assays showed a restorative effect of MPE-001 on the autophagic flux disrupted by NaIO3, which was associated with an increase in syntaxin 17-positive mature autophagosomes. The cytoprotective effect of MPE-001 was completely abolished by the autophagy inhibitors wortmannin and bafilomycin A1. In conclusion, we report for the first time an autophagy-dependent protection of RPE cells from oxidative stress by a CD36 ligand.


Assuntos
Antígenos CD36/metabolismo , Oligopeptídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular , Humanos , Iodatos/farmacologia , Ligantes , Terapia de Alvo Molecular , Oligopeptídeos/química , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/efeitos dos fármacos
17.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919990

RESUMO

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.


Assuntos
Degeneração Macular/tratamento farmacológico , Quercetina/farmacologia , Retina/efeitos dos fármacos , Doenças Retinianas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspase 3/genética , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Iodatos/toxicidade , Degeneração Macular/genética , Degeneração Macular/patologia , Mitocôndrias/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/genética , Espécies Reativas de Oxigênio/metabolismo , Retina/patologia , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/genética , Doenças Retinianas/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/crescimento & desenvolvimento , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/genética
18.
Anal Sci ; 37(11): 1517-1523, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33867404

RESUMO

We present an analytical method for dissolved oxygen based on the quantification of Mn(III) absorbance in a water sample. After Mn(II) reacts with the oxygen molecules in water, Mn(III) is formed and stabilized by hexa-metaphosphate under acidic conditions. The UV visible absorbance of Mn(III) is proportional to the oxygen concentration in the water sample. Compared to the Winkler method, the proposed method has the same accuracy (R = 0.9992 at 0 - 52 mg dm-3) but requires fewer reagents; furthermore, it does not involve titration. Interferences from nitrite and iodate were not observed. This procedure can be used to accurately and quickly determine the oxygen concentrations in different natural water sources, including seawater.


Assuntos
Oxigênio , Poluentes Químicos da Água , Iodatos , Oxigênio/análise , Água do Mar , Água , Poluentes Químicos da Água/análise
19.
Cell Death Dis ; 12(3): 230, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658488

RESUMO

Sodium iodate (SI) is a widely used oxidant for generating retinal degeneration models by inducing the death of retinal pigment epithelium (RPE) cells. However, the mechanism of RPE cell death induced by SI remains unclear. In this study, we investigated the necrotic features of cultured human retinal pigment epithelium (ARPE-19) cells treated with SI and found that apoptosis or necroptosis was not the major death pathway. Instead, the death process was accompanied by significant elevation of intracellular labile iron level, ROS, and lipid peroxides which recapitulated the key features of ferroptosis. Ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1(Fer-1) partially prevented SI-induced cell death. Further studies revealed that SI treatment did not alter GPX4 (glutathione peroxidase 4) expression, but led to the depletion of reduced thiol groups, mainly intracellular GSH (reduced glutathione) and cysteine. The study on iron trafficking demonstrated that iron influx was not altered by SI treatment but iron efflux increased, indicating that the increase in labile iron was likely due to the release of sequestered iron. This hypothesis was verified by showing that SI directly promoted the release of labile iron from a cell-free lysate. We propose that SI depletes GSH, increases ROS, releases labile iron, and boosts lipid damage, which in turn results in ferroptosis in ARPE-19 cells.


Assuntos
Ferroptose/efeitos dos fármacos , Iodatos/toxicidade , Oxidantes/toxicidade , Epitélio Pigmentado da Retina/efeitos dos fármacos , Linhagem Celular , Cisteína/metabolismo , Glutationa/metabolismo , Humanos , Ferro/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/ultraestrutura
20.
Water Res ; 193: 116851, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33540343

RESUMO

This study investigated the mechanisms of mixed IO3-/I- system under UV irradiation in drinking water and compared the iodinated trihalomethanes (I-THMs) formation of a mixed IO3-/I- system to that of single I- and IO3- systems during subsequent chloramination. The effects of initial I-/IO3- molar ratio, pH, and UV intensity on a mixed IO3-/I- system were studied. The introduction of I- enhanced the conversion rate of IO3- to reactive iodine species (RIS). Besides, IO3- degradation rate increased with the increase of initial I- concentration and UV intensity and the decrease of pH value. In a mixed IO3-/I- system, IO3- could undergo direct photolysis and photoreduction by hydrated electron (eaq-). Moreover, the enhancement of I-THM formation in a mixed IO3-/I- system during subsequent chloramination was observed. The I-THM yields in a mixed IO3-/I- system were higher than the sum of I-THMs produced in a single IO3- and I- systems at all the evaluated initial I- concentrations and pH values. The difference between I-THM formation in a mixed IO3-/I- system and the sum of I-THMs in a single IO3- and I- systems increased with the increase of initial I- concentration. As the initial pH decreased from 9 to 5, the difference of I-THM yields enhanced, while the total I-THM yield of a mixed IO3-/I- system and single I- and IO3- systems decreased slightly. Besides, IO3--I--containing water with DOC concentration of 2.5-4.5 mg-C/L, which mainly contained humic-acid substances, had a higher risk in I-THMs formation than individual I--containing and IO3--containing water.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Iodatos , Iodetos , Fotólise , Trialometanos/análise , Água , Poluentes Químicos da Água/análise
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