Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 573
Filtrar
1.
Water Res ; 194: 116951, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33640749

RESUMO

Highly toxic iodinated phenolic by-products were frequently detected in the oxidative treatment and disinfection of iodine-containing water. Herein, it was found that three model iodinated phenolic disinfection byproducts (DBPs), 2-iodophenol, 4-iodophenol and 2,4,6-triiodophenol, were reactive with HOCl, and the reaction rate constants (at pH 7.0 and 25℃) were 1.86 ×102, 1.62 ×102 and 7.5 ×101 M-1s-1, respectively. When HOCl was in excess (HOCl/iodophenol = 40/1, [iodophenol]0 = 20 µM), acute toxicity of water sample containing iodophenols could be largely eliminated (> 85%), with the conversion of iodophenols into stable and non-toxic iodate (IO3-) and iodinated and chlorinated aliphatic DBPs. Besides IO3-, seven kinds of aromatic intermediate products including iodophenols, chloroiodophenols, iodoquinones, chloroiodoquinones, chloroquinones, chlorophenols, and coupling products were detected. C-I bond of iodophenols was cleaved in the reaction and the resulted aromatic products were further transformed into chlorinated aliphatic DBPs [trichloromethane (TCM), trichloroacetic acid (TCAA), dichloroacetic acid (DCAA), and chloral hydrate (CH)] (mg/L level) and iodinated trihalomethanes (µg/L level). HOCl was effective for converting iodophenols into IO3- and less toxic chlorinated aliphatic DBPs. Considering that chlorine was widely used as disinfectant, transformation and toxicity alteration of emerging DBPs during chlorination/booster chlorination warrant further investigations.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção , Halogenação , Iodatos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
2.
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
3.
Food Chem ; 336: 127708, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768908

RESUMO

Smartphone digital image colorimetry (SDIC), combined with solidification of floating organic drop-dispersive liquid-liquid microextraction (SFOD-DLLME), was proposed for the determination of iodate ions. A colorimetric box was designed to capture images of sample solutions. Factors affecting the efficiency of SDIC included type of phone, region of interest, position of camera, and distance between camera and sample solution. Optimum SFOD-DLLME conditions were achieved with 1-undecanol (500 µL) as the extraction solvent, ethanol (1.5 mL) as the disperser solvent within 20 s extraction time. Limit of detection (LOD) was found as 0.1 µM (0.2 µg g-1) and enrichment factors ranged between 17.4 and 25.0. Calibration graphs showed good linearity with coefficients of determination higher than 0.9954 and relative standard deviations lower than 5.6%. The proposed method was efficiently applied to determine iodate in table salt samples with percentage relative recoveries ranging between 89.3 and 109.3%.


Assuntos
Análise de Alimentos/métodos , Iodatos/análise , Microextração em Fase Líquida/métodos , Smartphone , Cloreto de Sódio na Dieta/análise , Calibragem , Colorimetria/instrumentação , Colorimetria/métodos , Análise de Alimentos/instrumentação , Processamento de Imagem Assistida por Computador , Limite de Detecção , Microextração em Fase Líquida/instrumentação , Solventes/química
4.
Phytomedicine ; 80: 153375, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33096452

RESUMO

BACKGROUND: Dry age-related macular degeneration (dAMD) leads to serious burden of visual impairment and there is no definitive treatment. Previous studies have showed that naringenin (NAR) significantly increased electroretinography (ERG) c-wave in sodium iodate (NaIO3)-treated rats and viability of NaIO3-treated ARPE-19 cells. But the underlying mechanism is still unknown. PURPOSE: We tested the hypothesis that anti-oxidation mediated by Sirtuin 1 (SIRT1) was important to the protective effect of NAR on dAMD. STUDY DESIGN/METHODS: NaIO3-induced mice retinopathy and ARPE-19 cells injury models were established. In vivo, the protective effect of NAR eye drops on retina was evaluated by flash ERG (FERG) recording and histopathological examination. In vitro, viability of ARPE-19 cells, and the levels of lactic dehydrogenase (LDH), reactive oxygen species (ROS) and carbonyl protein were detected. Protein expression of SIRT1 was analyzed by immunochemical staining, immunofluorescence and western blotting. RESULTS: NAR eye drops improved retinal function and morphology and normalized the protein expression of SIRT1 in mice exposed to NaIO3. NAR promoted the survival of ARPE-19 cells in a concentration-dependent manner. NAR up-regulated SIRT1 protein expression, and decreased levels of ROS and carbonyl protein. Moreover, EX527, a selective inhibitor of SIRT1, abolished the effects of NAR on the cell viability and ROS. In addition, SRT1720, a selective agonist of SIRT1, improved the viability of cells and suppressed the production of ROS. CONCLUSION: Our findings indicate that SIRT1-mediated anti-oxidation contributes to the protective effect of NAR eye drops on dAMD.


Assuntos
Flavanonas/farmacologia , Substâncias Protetoras/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Carbazóis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Iodatos/toxicidade , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Soluções Oftálmicas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/tratamento farmacológico , Epitélio Pigmentado da Retina/citologia , Regulação para Cima/efeitos dos fármacos
5.
Chemosphere ; 266: 129104, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33310356

RESUMO

Radioactive iodine (129I) is of great concern owing to its high mobility in the environment and long-term radiotoxicity. However, there is a lack of effective techniques for removing iodate (IO3-) from aqueous solution. This study aims to develop a new technique for removing radioactive iodate from contaminated solution by using barite (BaSO4). We examined the coprecipitation mechanism of iodate by barite at the molecular level to determine the optimum conditions for iodate removal. Results showed that iodate was effectively removed from the aqueous solution by coprecipitation even in the presence of competitive anions. Based on comparison of our method with previous techniques, the iodate removal efficiency by barite was determined to be about two orders of magnitude greater than that by hydrotalcite-like layered double hydroxide at 10 mmol L-1 Cl-. Extended X-ray absorption fine structure analysis indicated that the incorporated iodate was strongly bound to the crystal lattice of barite by substituting the sulfate site in the structure when the iodine concentration was low. The charge compensation problem from the IO3- substitution in the SO42- site was achieved by the substitution of Na+-IO3- pairs at the nearest Ba2+ site. Given the high removal efficiency and strong binding of iodate to barite, coprecipitation with barite is a promising tool for removing radioactive iodate from various aqueous solutions contaminated with iodate.


Assuntos
Iodatos , Neoplasias da Glândula Tireoide , Sulfato de Bário , Humanos , Radioisótopos do Iodo , Sulfatos
6.
Biomed Pharmacother ; 133: 111041, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378949

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1)-dependent cell death in the retinal pigment epithelium (RPE) is implicated in dry age-related macular degeneration (AMD). Although PARP1 inhibitors are available for treating dry AMD, their delivery route is not ideal for patients. The aim of this study was to test the efficacy of a novel PARP1-inhibitory compound (PIC) in vitro and in vivo. This study presents PIC, a novel small molecule, with superior efficacy to PARP1 inhibitors in the market. PIC demonstrated a distinctive inhibitory profile against PARP isotypes than the FDA-approved PARP1 inhibitors. PIC inhibited PARP1 activation at an IC50 of 0.41 ± 0.15 nM in an enzyme-based assay in vitro and at IC50 and EC50 in ARPE-19 cells of 0.11 ± 0.02 nM and 0.22 ± 0.02 nM, respectively, upon H2O2 insult. PIC also moderated mitochondrial fission and depolarization and maintained cellular energy levels under oxidative stress in ARPE-19 cells. Furthermore, PIC demonstrated good corneal penetration in a rat model, presenting PIC as a promising candidate for eye drop therapeutics for dry AMD. When PIC was administered as an eye drop formulation, RPE morphology was preserved, maintaining the thickness of the outer nuclear layers under sodium iodate (SI) treatment in rats. In SI-treated rabbits, eye drop administration of PIC also retained the structural and functional integrity when analyzed using funduscopy and electroretinogram. Collectively, our data portray PIC as an attractive treatment measure for dry AMD.


Assuntos
Degeneração Macular/tratamento farmacológico , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Administração Oftálmica , Animais , Antioxidantes/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Iodatos , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Degeneração Macular/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Absorção Ocular , Soluções Oftálmicas , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Coelhos , Ratos Sprague-Dawley , Epitélio Pigmentado da Retina/enzimologia , Epitélio Pigmentado da Retina/patologia
7.
Sci Rep ; 10(1): 8688, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457394

RESUMO

Epidemiological studies indicate that the daily intake of antioxidants from a traditional Asian diet reduces the risk of developing age-related macular degeneration. Many of the phytochemicals that are abundant in whole grains exhibit a wide variety of biological activity such as antioxidant, anti-inflammatory, and neuroprotective effects. Ferulic acid (FA) is a phenolic acid found in vegetables and grains that has therapeutic potential for diabetes mellitus, Alzheimer's disease, and other diseases. We investigated the retinal protective effect of FA in a sodium iodate (NaIO3)-induced model of retinal degeneration. In a human retinal pigment epithelial cell line, FA attenuated H2O2-induced injury and lipopolysaccharide- or 7-ketocholesterol-induced inflammation. In mice, the oral administration of FA or its analog, ethyl ferulate, attenuated the morphological and functional features of NaIO3-induced retinal degeneration according to optical coherence tomography and electroretinography. Our results demonstrate that the oral administration of FA provides protective effects to the retina, suggesting that the intake of FA as a daily supplement or daily healthy diet containing rich vegetables and whole grains may prevent age-related macular degeneration.


Assuntos
Ácidos Cafeicos/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Degeneração Retiniana/prevenção & controle , Administração Oral , Animais , Ácidos Cafeicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Eletrorretinografia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Iodatos/toxicidade , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Retina/diagnóstico por imagem , Retina/metabolismo , Retina/patologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia , Tomografia de Coerência Óptica
8.
Chemosphere ; 253: 126743, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464777

RESUMO

In coastal regions, intense bursts of particles are frequently observed with high concentrations of iodine species, especially iodic acid (IA). However, the nucleation mechanisms of IA, especially in polluted environments with high concentrations of sulfuric acid (SA) and ammonia (A), remain to be fully established. By quantum chemical calculations and atmospheric cluster dynamics code (ACDC) simulations, the self-nucleation of IA in clean coastal regions and that influenced by SA and A in polluted coastal regions are investigated. The results indicate that IA can form stable clusters stabilized by halogen bonds and hydrogen bonds through sequential addition of IA, and the self-nucleation of IA can instantly produce large amounts of stable clusters when the concentration of IA is high during low tide, which is consistent with the observation that intense particle bursts were linked to high concentrations of IA in clean coastal regions. Besides, SA and A can stabilize IA clusters by the formation of more halogen bonds and hydrogen bonds as well as proton transfers, and the binary nucleation of IA-SA/A rather than the self-nucleation of IA appears to be the dominant pathways in polluted coastal regions, especially in winter. These new insights are helpful to understand the mechanisms of new particle formation induced by IA in clean and polluted coastal regions.


Assuntos
Poluentes Ambientais/análise , Iodatos/química , Amônia , Atmosfera/química , Poluição Ambiental , Ligação de Hidrogênio , Modelos Químicos , Ácidos Sulfúricos
9.
J Appl Microbiol ; 128(5): 1378-1389, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31916379

RESUMO

AIMS: To determine the mechanism of killing of spores of Bacillus thuringiensis Al Hakam, a Bacillus anthracis spore surrogate, in a blast environment with or without HIO3 and whether the spores are truly dead. METHODS AND RESULTS: Spores exposed to an aluminium-based blast environment with or without HIO3 with dynamic peak gas phase temperatures near 1000°C persisting for 10's of ms, were killed 97 and 99·99% without and with HIO3 respectively and the spores were truly dead. The survivors of the detonations did not acquire mutations, did not become wet heat sensitive, became sensitive to elevated NaCl but not lack of glucose in recovery media, and many dead spores remained phase bright and retained their Ca-dipicolinic acid. A large fraction of the dead spores could germinate, but most of these germinated spores were dead. CONCLUSIONS: Most spores exposed to a blast environment are truly dead, and HIO3 increases spore death. The likely mechanism of spore killing in these blast environments is damage to some essential spore protein, although spore inner membrane damage could contribute. SIGNIFICANCE AND IMPACT OF THE STUDY: This work shows that spores of a surrogate for B. anthracis spores are killed in a blast environment without or with HIO3 present, this approach could inactivate up to 99·99% of dry B. anthracis spores, and the spores are likely killed by damage to some essential spore protein.


Assuntos
Bacillus thuringiensis/efeitos dos fármacos , Bacillus thuringiensis/fisiologia , Descontaminação/métodos , Explosões , Iodatos/farmacologia , Bacillus anthracis/efeitos dos fármacos , Bacillus anthracis/fisiologia , Temperatura Alta , Viabilidade Microbiana , Ácidos Picolínicos/metabolismo , Cloreto de Sódio , Esporos Bacterianos/efeitos dos fármacos , Esporos Bacterianos/fisiologia
10.
Sci Rep ; 9(1): 15696, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666618

RESUMO

We sought to develop and characterize outer retinal degeneration induced by intravitreal injection of sodium iodate (SI) after vitrectomy in rabbits. To determine the effective dose of SI, the right eyes of 19 male New Zealand white rabbits received an intravitreal injection of SI or sham. Based on the dose-dependence results, 0.4 mg of SI in 0.05 mL of total volume was injected into the right eyes of 10 rabbits at two weeks after vitrectomy. In the dose-dependence study, localized retinal atrophy was observed with 0.3- and 0.4-mg SI injections without vitrectomy. Severe and diffuse retinal atrophy was identified by spectral-domain optical coherence tomography (SD-OCT) at one month after a 0.5-mg SI injection following vitrectomy. In the second experiment, 0.4 mg of SI in 0.05 mL was injected, and the severity of outer retinal degeneration was graded as one of two types according to electroretinography (ERG) response change. There was no response on ERG in complete retinal degeneration, 30% of all 10 rabbits. Intravitreal injection of 0.4 mg of SI into vitrectomized rabbit eyes induces diffuse outer retinal degeneration, and the degree of retinal degeneration can be evaluated through in vivo ophthalmic examination.


Assuntos
Iodatos/farmacologia , Retina/efeitos dos fármacos , Degeneração Retiniana/tratamento farmacológico , Corpo Vítreo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrorretinografia , Humanos , Injeções Intravítreas , Coelhos , Retina/diagnóstico por imagem , Retina/patologia , Degeneração Retiniana/patologia , Degeneração Retiniana/cirurgia , Tomografia de Coerência Óptica , Vitrectomia/métodos , Corpo Vítreo/diagnóstico por imagem , Corpo Vítreo/cirurgia
11.
Int J Mol Sci ; 20(19)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569695

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.


Assuntos
Lipoproteínas HDL/metabolismo , Peptídeos/farmacologia , Células Fotorreceptoras/efeitos dos fármacos , Células Fotorreceptoras/metabolismo , Degeneração Retiniana/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Caspase 7/metabolismo , Modelos Animais de Doenças , Iodatos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/etiologia , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica
12.
J Photochem Photobiol B ; 198: 111561, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352000

RESUMO

Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.


Assuntos
Iodatos/toxicidade , Transplante de Células-Tronco Mesenquimais , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Polpa Dentária/citologia , Modelos Animais de Doenças , Eletrorretinografia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células Fotorreceptoras/citologia , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/etiologia , Epitélio Pigmentado da Retina/patologia
13.
Environ Sci Pollut Res Int ; 26(23): 23850-23860, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31214887

RESUMO

The environmental fate of iodine is of general geochemical interest as well as of substantial concern in the context of nuclear waste repositories and reprocessing plants. Soils, and in particular soil organic matter (SOM), are known to play a major role in retaining and storing iodine. Therefore, we investigated iodide and iodate sorption by four different reference soils for contact times up to 30 days. Selective sequential extractions and X-ray absorption spectroscopy (XAS) were used to characterize binding behavior to different soil components, and the oxidation state and local structure of iodine. For iodide, sorption was fast with 73 to 96% being sorbed within the first 24 h, whereas iodate sorption increased from 11-41% to 62-85% after 30 days. The organic fraction contained most of the adsorbed iodide and iodate. XAS revealed a rapid change of iodide into organically bound iodine when exposed to soil, while iodate did not change its speciation. Migration behavior of both iodine species has to be considered as iodide appears to be the less mobile species due to fast binding to SOM, but with the potential risk of mobilization when oxidized to iodate.


Assuntos
Iodatos/química , Iodo/química , Solo/química , Adsorção , Iodetos/química , Oxirredução , Espectroscopia por Absorção de Raios X
14.
J Photochem Photobiol B ; 196: 111514, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31154277

RESUMO

Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration.


Assuntos
Iodatos/toxicidade , Retina/efeitos dos fármacos , Degeneração Retiniana/patologia , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Eletrorretinografia , Ratos , Ratos Sprague-Dawley , Retina/patologia , Retina/fisiologia
15.
J Biomed Sci ; 26(1): 40, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118030

RESUMO

BACKGROUND: Oxidative stress is a major factor in retinal pigment epithelium (RPE) cells injury that contributes to age-related macular degeneration (AMD). NaIO3 is an oxidative toxic agent and its selective RPE cell damage makes it as a reproducible model of AMD. Although NaIO3 is an oxidative stress inducer, the roles of ROS in NaIO3-elicited signaling pathways and cell viability have not been elucidated, and the effect of NaIO3 on autophagy in RPE cells remains elusive. METHODS: In human ARPE-19 cells, we used Annexin V/PI staining to determine cell viability, immunoblotting to determine protein expression and signaling cascades, confocal microscopy to determine mitochondrial dynamics and mitophagy, and Seahorse analysis to determine mitochondrial oxidative phosphorylation. RESULTS: We found that NaIO3 can dramatically induce cytosolic but not mitochondrial ROS production. NaIO3 can also activate ERK, p38, JNK and Akt, increase LC3II expression, induce Drp-1 phosphorylation and mitochondrial fission, but inhibit mitochondrial respiration. Confocal microscopic data indicated a synergism of NaIO3 and bafilomycin A1 on LC3 punctate formation, indicating the induction of autophagy. Using cytosolic ROS antioxidant NAC, we found that p38 and JNK are downstream signals of ROS and involve in NaIO3-induced cytotoxicity but not in mitochondrial dynamics, while ROS is also involved in LC3II expression. Unexpectedly NAC treatment upon NaIO3 stimulation leads to an enhancement of mitochondrial fragmentation and cell death. Moreover, inhibition of autophagy and Akt further enhances cell susceptibility to NaIO3. CONCLUSIONS: We conclude that NaIO3-induced oxidative stress and cytosolic ROS production exert multiple signaling pathways that coordinate to control cell death in RPE cells. ROS-dependent p38 and JNK activation lead to cytotoxicity, while ROS-mediated autophagy and mitochondrial dynamic balance counteract the cell death mechanisms induced by NaIO3 in RPE cells.


Assuntos
Autofagia/fisiologia , Iodatos/toxicidade , Degeneração Macular/fisiopatologia , Dinâmica Mitocondrial/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/fisiopatologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estresse Oxidativo/fisiologia , Epitélio Pigmentado da Retina/efeitos dos fármacos
16.
Molecules ; 24(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30988267

RESUMO

A useful method for the synthesis of 2-acylamino-1,3,4-oxadiazoles was developed. By using potassium iodate as an oxidant in water at 60 °C, a wide range of 2-acylamino-1,3,4-oxadiazoles were afforded in moderate to excellent yields within two hours. This method could provide a facile shortcut to generate a series of 2-acylamino-1,3,4-oxadiazoles in medicinal chemistry. Interestingly, some highly potent antibiotic compounds were found through this synthetic method, and some of them displayed a significant improvement in activity compared with the corresponding 1,4-diacylthiosemicarbazides. Compound 2n was the most active against Staphylococcus aureus with MIC (minimum inhibitory concentration) of 1.56 mg/mL, and compounds 2m and 2q were the most active against Bacillus subtilis with MIC of 0.78 mg/mL. The preliminary cytotoxic activities of the most potent compounds 2m, 2n, and 2q against the androgen-independent (PC-3) prostate cancer cell line were more than 30 µM (IC50 > 30 µM).


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Iodatos/química , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Compostos de Potássio/química , Semicarbazidas/química , Bactérias/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Testes de Sensibilidade Microbiana
17.
J Cell Mol Med ; 23(5): 3495-3504, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30821111

RESUMO

Glycyrrhizin is a bioactive triterpenoid saponin extracted from a traditional Chinese medicinal herb, glycyrrhiza, and has been reported to protect the organs such as liver and heart from injuries. However, there is no report about the effects of glycyrrhizin on atrophic age-related macular degeneration (AMD). This study investigated the effects of glycyrrhizin on retinal pigment epithelium (RPE) in vitro and retina of mice in vivo treated with sodium iodate (SI). Glycyrrhizin significantly inhibited SI-induced reactive oxygen species (ROS), and decreased apoptosis of RPE in vitro. The underlying mechanisms included increased phosphorylation of Akt, and increased expression of nuclear factor erythroid 2-related factor2 (Nrf-2) and HO-1, thereby protecting RPE from SI-induced ROS and apoptosis. Furthermore, glycyrrhizin significantly decreased the apoptosis of retinal cells in vivo, resulting in the inhibition of thinning of retina, decreasing the number of drusen and improving the function of retina. These findings suggested that glycyrrhizin may be a potential candidate for the treatment of atrophic AMD in clinical practice.


Assuntos
Ácido Glicirrízico/farmacologia , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Retina/efeitos dos fármacos , Doenças Retinianas/prevenção & controle , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Iodatos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Retina/metabolismo , Retina/patologia , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais/efeitos dos fármacos
18.
Environ Sci Technol ; 53(9): 4892-4900, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30916540

RESUMO

A new mechanism for the abiotic production of molecular iodine (I2) from iodate (IO3-), which is the most abundant iodine species, in dark conditions was identified and investigated. The production of I2 in aqueous solution containing IO3- and nitrite (NO2-) at 25 °C was negligible. However, the redox chemical reaction between IO3- and NO2- rapidly proceeded in frozen solution at -20 °C, which resulted in the production of I2, I-, and NO3-. The rapid redox chemical reaction between IO3- and NO2- in frozen solution is ascribed to the accumulation of IO3-, NO2-, and protons in the liquid regions between ice crystals during freezing (freeze concentration effect). This freeze concentration effect was verified by confocal Raman microscopy for the solute concentration and UV-visible absorption spectroscopy with cresol red (acid-base indicator) for the proton concentration. The freezing-induced production of I2 in the presence of IO3- and NO2- was observed under various conditions, which suggests this abiotic process for I2 production is not restricted to a specific region and occurs in many cold regions. NO2--induced activation of IO3- to I2 in frozen solution may help explain why the measured values of iodine are larger than the modeled values in some polar areas.


Assuntos
Iodatos , Iodo , Congelamento , Iodetos , Nitritos
19.
Nutrients ; 11(2)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795581

RESUMO

The use of iodine-biofortified vegetables may be a health alternative instead of iodine-biofortified salt for preventing iodine (I) deficiency and related human disorders. In this study, four Brassica genotypes (broccoli raab, curly kale, mizuna, red mustard) were hydroponically grown with three I-IO3- rates (0, 0.75 and 1.5 mg/L) to produce iodine-biofortified vegetables. Crop performances and quality traits were analyzed; iodine content was measured on raw, boiled, and steamed vegetables. The highest I rate generally increased I content in all Brassica genotypes, without plants toxicity effects in terms of reduced growth or morphological symptoms. After 21 day-iodine biofortification, the highest I content (49.5 µg/100 g Fresh Weight (FW)) was reached in broccoli raab shoots, while after 43 day-iodine biofortification, genotype differences were flattened and the highest I content (66 µg/100 g FW, on average) was obtained using 1.5 mg I-IO3/L. Nitrate content (ranging from 1800 to 4575 mg/kg FW) was generally higher with 0.75 mg I-IO3/L, although it depended on genotypes. Generally, boiling reduced iodine content, while steaming increased or left it unchanged, depending on genotypes. Applying low levels of I proved to be suitable, since it could contribute to the partial intake of the recommended dose of 150 µg/day: A serving size of 100 g may supply on average 24% of the recommended dose. Cooking method should be chosen in order to preserve and/or enhance the final I amount.


Assuntos
Biofortificação/métodos , Brassica/metabolismo , Alimentos Fortificados , Genótipo , Iodatos/metabolismo , Iodo/metabolismo , Compostos de Potássio/metabolismo , Verduras/química , Brassica/genética , Culinária , Deficiências Nutricionais/prevenção & controle , Dieta , Ingestão de Energia , Humanos , Hidroponia , Iodo/administração & dosagem , Iodo/deficiência , Nitratos/metabolismo , Brotos de Planta/metabolismo , Especificidade da Espécie
20.
Free Radic Biol Med ; 135: 116-124, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735837

RESUMO

Hydrogen possesses antioxidative effects and cures numerous types of ophthalmopathy, but the mechanism of hydrogen on ROS-induced retinal senescence remains elusive. In this study, retinal morphology revealed that hydrogen reduced the number and size of vitreous black deposits in Bruch's membrane in NaIO3 mice. Hydrogen also reduced ROS levels in the retina as assessed by DHE staining. Moreover, this result was consistent with the downregulation of expression of the oxidative stress hallmark OGG1. These findings suggested that hydrogen can reduce retinal oxidative stress induced by NaIO3, and this result was further verified using the antioxidant ALCAR. Mechanistic analysis revealed that hydrogen significantly inhibited the downregulation of Sirt3 expression, and this notion was confirmed using AICAR, which restores Sirt3 expression and activity. Moreover, hydrogen reduced the expression of p53, p21 and p16 and the number of blue-green precipitations in the retinas of NaIO3 mice as assessed by SA-ß-gal staining. We also found that hydrogen decreased the expression of the DNA damage-related protein ATM, cyclinD1 and NF-κB but increased the expression of the DNA repair-related protein HMGB1, suggesting that hydrogen inhibits senescence in retinas of NaIO3 mice. Additionally, OCT examination revealed that hydrogen suppressed retinal high reflex formation significantly and prevented the retina from thinning. This result was supported by ERG assays that demonstrated that hydrogen prevented the reduction in a- and b-wave amplitude induced by NaIO3 in mice. Thus, our data suggest that hydrogen may inhibit retinal senescence by suppressing the downregulation of Sirt3 expression through reduced oxidative stress reactions.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/metabolismo , Retina/metabolismo , Sirtuína 3/genética , Acetilcarnitina/farmacologia , Envelhecimento/genética , Animais , Antioxidantes/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Ciclina D1/genética , Dano ao DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/genética , Humanos , Hidrogênio/efeitos adversos , Iodatos/toxicidade , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Retina/efeitos dos fármacos , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/genética , Degeneração Retiniana/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...