RESUMO
Membrane phospholipids play pivotal roles in various cellular processes, and their levels are tightly regulated. In the retina, phospholipids had been scrutinized because of their distinct composition and requirement in visual transduction. However, how lipid composition changes during retinal development remains unclear. Here, we used liquid chromatography-mass spectrometry (LC-MS) to assess the dynamic changes in the levels of two main glycerophospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), in the developing mouse retina under physiological and pathological conditions. The total levels of PC and PE increased during retinal development, and individual lipid species exhibited distinct level changes. The amount of very-long-chain PC and PE increased dramatically in the late stages of retinal development. The mRNA levels of Elovl2 and Elovl4, genes encoding enzymes essential for the synthesis of very-long-chain polyunsaturated fatty acids, increased in developing photoreceptors. Cell sorting based on CD73 expression followed by LC-MS revealed distinct changes in PC and PE levels in CD73-positive rod photoreceptors and CD73-negative retinal cells. Finally, using the NaIO3-induced photoreceptor degeneration model, we identified photoreceptor-specific changes in PC and PE levels from 1 day after NaIO3 administration, before the outer segment of photoreceptors displayed morphological impairment. In conclusion, our findings provide insight into the dynamic changes in PC and PE levels in the developing and adult mouse retina under physiological and pathological conditions. Furthermore, we provide evidence that cell sorting followed by LC-MS is a promising approach for investigating the relevance of lipid homeostasis in the function of different retinal cell types.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Lipídeos de Membrana/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Degeneração Retiniana/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Cromatografia Líquida , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Citometria de Fluxo , Iodatos/administração & dosagem , Espectrometria de Massas , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Organogênese/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Bastonetes/citologiaRESUMO
Purpose: To observe the effects of tetramethylpyrazine (TMP) on mice retinas injured by sodium iodate (NaIO3). Methods: Male mice (n = 45) were randomly divided into three groups: the control group (Group C), the NaIO3-degenerated group (Group I), and the TMP-treated group (TMP group). The Group I mice were intraperitoneally injected with 35 mg/kg NaIO3. The Group C mice were injected with similar volumes of PBS. The TMP group mice were intraperitoneally injected with 80 mg/kg TMP starting 24 h after NaIO3 administration once a day for 14 days. Fundus photography, optical coherence tomography (OCT), electroretinography (ERG), hematoxylin and eosin (H&E) staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blotting were used to assess the effects of TMP on mice retinas at day 3, 7, and 14 after NaIO3 administration. Results: TMP effectively prevented the decrease in the thicknesses of the retinas and the outer nuclear layer (ONL), and effectively alleviated the functional decline in the retinas after NaIO3 administration. TMP significantly decreased the number of TUNEL-positive cells in retinas. In addition, TMP rapidly increased the expression of Nrf2 and HO-1 and decreased BAX expression in mice retinas after NaIO3 injection. Conclusions: TMP alleviates morphological and functional retinal damage in mice exposed to NaIO3 and reduces retinal apoptosis.
Assuntos
Degeneração Macular/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Pirazinas/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Modelos Animais de Doenças , Eletrorretinografia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Injeções Intraperitoneais , Iodatos/administração & dosagem , Degeneração Macular/induzido quimicamente , Degeneração Macular/genética , Degeneração Macular/patologia , Masculino , Proteínas de Membrana/agonistas , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Resultado do Tratamento , Proteína X Associada a bcl-2/antagonistas & inibidores , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Rationale: The Notch and transforming growth factor-ß (TGFß) signaling pathways are two intracellular mechanisms that control fibrosis in general but whether they play a major role in retinal fibrosis is less clear. Here we study how these two signaling pathways regulate Müller cell-dominated retinal fibrosis in vitro and in vivo. Methods: Human MIO-M1 Müller cells were treated with Notch ligands and TGFß1, either alone or in combination. Western blots were performed to study changes in γ-secretase proteases, Notch downstream effectors, endogenous TGFß1, phosphorylated Smad3 (p-Smad3) and extracellular matrix (ECM) proteins. We also studied the effects of RO4929097, a selective γ-secretase inhibitor, on expression of ECM proteins after ligand stimulation. Müller cell viability was studied by AlamarBlue and cytotoxicity by lactate cytotoxicity assays. Finally, we studied changes in Notch and TGFß signaling and tested the effect of intravitreal injections of the Notch pathway inhibitor RO4929097 on retinal fibrosis resulted from Sodium iodate (NaIO3)-induced retinal injury in mice. We also studied the safety of intravitreal injections of RO4929097 in normal mice. Results: Treatment of Müller cells with Notch ligands upregulated γ-secretase proteases and Notch downstream effectors, with increased expression of endogenous TGFß1, TGFß receptors and p-Smad3. TGFß1 upregulated the expression of proteins associated with both signaling pathways in a similar manner. Notch ligands and TGFß1 had additive effects on overexpression of ECM proteins in Müller cells which were inhibited by RO4929097. Notch and TGFß ligands stimulated Müller cell proliferation which was inhibited by RO4929097 without damaging the cells. NaIO3-induced retinal injury activated both Notch and TGFß signaling pathways in vivo. Intravitreal injection of RO4929097 prevented Müller cell gliosis and inhibited overexpression of ECM proteins in this murine model. We found no safety concerns for up to 17 days after an intravitreal injection of RO4929097. Conclusions: Inhibiting Notch signaling might be an effective way to prevent retinal fibrosis. This study is of clinical significance in developing a treatment for preventing fibrosis in proliferative vitreoretinopathy, proliferative diabetic retinopathy and wet age-related macular degeneration.
Assuntos
Benzazepinas/farmacologia , Células Ependimogliais/patologia , Gliose/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Benzazepinas/uso terapêutico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Células Ependimogliais/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Feminino , Fibrose , Gliose/induzido quimicamente , Gliose/patologia , Humanos , Injeções Intravítreas , Iodatos/administração & dosagem , Iodatos/toxicidade , Masculino , Camundongos , Receptores Notch/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Vitreorretinopatia Proliferativa/tratamento farmacológico , Vitreorretinopatia Proliferativa/patologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/patologiaRESUMO
BACKGROUND: KIO3 and KI are the most common salt iodization agents. Coincidentally, iodine exists naturally in high-iodine drinking water in the form of iodide (I-) or iodate (IO3-). As an oxidizing substance, IO3- should be reduced to I- before it can be effectively used by the thyroid. However, there is a lack of systematic studies on the metabolic process of high dose KIO3in vivo. METHODS: The iodine metabolism processes in the thyroid and serum of rats after high KIO3 intake were determined using high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) and arsenic cerium catalytic spectrophotometry. The changes of redox activity in the serum, thyroid, liver, and kidneys were observed by detecting total antioxidative activity (TAA). RESULTS: High doses of IO3- were completely reduced to I-in vivo within 0.5â¯h. The level of organic bound iodine in the serum was stable, while the organic bound iodine in the thyroid increased to a plateau after intake of high-dose KIO3. The levels of total iodine and I- in serum and thyroid increased quickly, then all decreased after reaching the maximum absorption peak, and I- had two absorption peaks in serum. The thyroid blocking dose of I- was 0.5â¯mg/kg in rat. Additionally, high KIO3 intake did not influence the TAA in serum and other tissues. CONCLUSION: The body is able to reduce and utilize high doses of KIO3 ingested through the digestive tract. The metabolism of high KIO3in vivo is characterized by two absorption process of I- in serum and the thyroid blocking effect. Moreover, a single intake of high-dose KIO3 does not affect TAA in vivo. The results suggest that such excess IO3- may have be reduced in the digestive tract before I-â¯enters the blood.
Assuntos
Antioxidantes/metabolismo , Iodatos/farmacologia , Iodo/metabolismo , Compostos de Potássio/farmacologia , Animais , Feminino , Iodatos/administração & dosagem , Iodatos/análise , Iodatos/sangue , Iodatos/farmacocinética , Iodo/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Compostos de Potássio/administração & dosagem , Compostos de Potássio/farmacocinética , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismoRESUMO
We developed and characterized a canine model of outer retinal degeneration induced by sodium iodate (SI) intravitreal injection after vitrectomy. In the preliminary study, we repeatedly injected SI intravitreally into the eyes of three canines to develop outer retinal degeneration two weeks after vitrectomy. Based on the preliminary study, a single dose of either 1.2 mg or 1.0 mg SI/0.05 mL was also injected (1.2 mg in n = 5 canines, 1.0 mg in n = 2 canines). Spectral domain-optical coherence tomography (OCT), electroretinography (ERG), and histological examinations were performed at baseline and following intravitreal injection. In the preliminary study, after a 0.5-mg SI injection and a 1.0-mg SI injection and after two 0.8-mg SI injections, retinal degeneration with retinal thinning was observed on OCT imaging. In the second study, after a single 1.0- or 1.2-mg SI injection, outer retinal degeneration was induced. All eyes showed diffuse outer retinal degeneration on OCT and a loss of both cone and rod responses in ERG. Histological examination also showed the loss of outer retinal layer. Intravitreally injected SI (1.0-1.2 mg) in a vitrectomized canine model induced outer retinal degeneration effectively, and could be evaluated through in vivo ophthalmic examination.
Assuntos
Iodatos/efeitos adversos , Degeneração Retiniana/etiologia , Animais , Modelos Animais de Doenças , Cães , Feminino , Humanos , Injeções Intravítreas , Iodatos/administração & dosagem , Retina/anatomia & histologia , Retina/diagnóstico por imagem , Retina/efeitos dos fármacos , Degeneração Retiniana/diagnóstico por imagem , Degeneração Retiniana/fisiopatologia , Tomografia de Coerência Óptica , VitrectomiaRESUMO
BACKGROUND: Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodine supplementation overall, and of different forms and dosages of iodine supplementation separately, in the prevention of iodine deficiency disorders in children. SEARCH METHODS: The Cochrane Library, MEDLINE, EMBASE and reference lists, databases of ongoing trials and the Internet were searched. SELECTION CRITERIA: We included randomised controlled trials and prospective controlled trials not using randomisation of iodine supplementation in children living in areas of iodine deficiency. DATA COLLECTION AND ANALYSIS: Two reviewers did the initial data selection and quality assessment of trials independently. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: Twenty-six prospective controlled trials were related to our question, assessing a total of 29613 children. Twenty of them were classified as being of low quality, six of moderate quality. Most studies used iodised oil as a supplement, but other supplements were also used. The intervention groups were compared to a non-supplemented control group, different doses or different forms of iodine supplementation.There was a clear tendency towards goitre reduction with iodine supplementation; this was significant in several studies. Significant differences in physical development were not seen, except in one study. Results for differences in cognitive and psychomotor measures were mixed, with only few studies showing a positive intervention effect. One study suggested that infant mortality was lowered after iodine supplementation.Most studies showed a significant increase in urinary iodine excretion and levels recommended by the WHO were reached in most cases after supplementation. Thyroid-stimulating hormone (TSH) levels were significantly reduced in one study. In 1.8% of the children investigated, adverse effects were found, most of them were minor and transient. AUTHORS' CONCLUSIONS: Despite most of the included studies being of low quality, the results suggest that iodine supplementation, especially iodised oil, is an effective means of decreasing goitre rates and improving iodine status in children. Indications of positive effects on physical and mental development and mortality were seen, although results were not always significant. Adverse effects were generally minor and transient. Insufficient evidence was available on non-oil supplements. High quality controlled studies investigating relevant long term outcome measures are needed to address the question of the best form of iodine supplementation in different population groups and settings.
Assuntos
Suplementos Nutricionais , Bócio/prevenção & controle , Iodo/administração & dosagem , Iodo/deficiência , Criança , Hipotireoidismo Congênito/prevenção & controle , Ensaios Clínicos Controlados como Assunto , Suplementos Nutricionais/efeitos adversos , Humanos , Iodatos/administração & dosagem , Iodo/efeitos adversos , Óleo Iodado/administração & dosagem , Mixedema/prevenção & controle , Compostos de Potássio/administração & dosagem , Iodeto de Potássio/administração & dosagem , Cloreto de Sódio na Dieta/administração & dosagemRESUMO
Purpose: To determine the mechanism causing degeneration of the retinal pigment epithelium (RPE) and photoreceptors in mice after an intravenous injection of sodium iodate (NaIO3). Methods: The time-dependent changes in NaIO3-induced retinal degeneration were determined by analyzing the retinal morphology by optical coherence tomographic (OCT) images, histological sections of the retina, physiology of the retina by electroretinography (ERG), and retinal blood flow by laser speckle flowgraphy. In addition, the expression of the genes associated with age-related macular degeneration in humans was assessed in the NaIO3-treated mice by RT-PCR. We also investigated whether macrophages were involved in the NaIO3-induced retinal degeneration. Results: The intravenous injection of 20 mg/kg NaIO3 altered the morphology of the RPE cells and the ERGs transiently. With 40 mg/kg of NaIO3, the degeneration of the RPE cells was still present at 28 days. Aggregated melanin granules were surrounded by zonula occludens protein 1 (ZO-1)-positive cells. In addition, 40 mg/kg of NaIO3 led to a reduction in the amplitudes of the a- and b-waves of the dark-adapted ERGs. Histological studies showed that macrophages had infiltrated the retina and were present around the altered RPE cells. Depletion of the macrophages by a prior injection of clodronate liposomes prevented the damage of the outer retina after the NaIO3 injection but not the RPE. Conclusions: The NaIO3-induced retinal damage was reversible at low concentrations but permanent at high concentrations of NaIO3. The accumulation of macrophages around the RPE cells caused the photoreceptor cell death.
Assuntos
Iodatos/toxicidade , Macrófagos/metabolismo , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Degeneração Retiniana/induzido quimicamente , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Apoptose , Modelos Animais de Doenças , Eletrorretinografia , Angiofluoresceinografia , Marcação In Situ das Extremidades Cortadas , Injeções Intravenosas , Iodatos/administração & dosagem , Fluxometria por Laser-Doppler , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patologia , Reação em Cadeia da Polimerase em Tempo Real , Degeneração Retiniana/diagnóstico por imagem , Degeneração Retiniana/metabolismo , Epitélio Pigmentado da Retina/diagnóstico por imagem , Epitélio Pigmentado da Retina/metabolismo , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: Low doses of sodium iodate (NaIO3) impair visual function in experimental animals with selective damage to retinal pigment epithelium (RPE) and serve as a useful model to study diseases caused by RPE degeneration. Mitochondrial dysfunction and defective autophagy have been suggested to play important roles in normal aging as well as many neurodegenerative diseases. In this study, we examined whether NaIO3 treatment disrupted the mitochondrial-lysosomal axis in cultured RPE. METHODS: The human RPE cell line, ARPE-19, was treated with low concentrations (≤500 µM) of NaIO3. The expression of proteins involved in the autophagic pathway and mitochondrial biogenesis was examined with Western blot. Intracellular acidic compartments and lipofuscinogenesis were evaluated by acridine orange staining and autofluorescence, respectively. Mitochondrial mass, mitochondrial membrane potential (MMP), and mitochondrial function were quantified by MitoTracker Green staining, tetramethylrhodamine methyl ester staining, and the MTT assay, respectively. Phagocytosis and the degradation of photoreceptor outer segments (POS) were assessed by fluorescence-based approaches and Western blot against rhodopsin. RESULTS: Treatment with low concentrations of NaIO3 decreased cellular acidity, blocked autophagic flux, and resulted in increased lipofuscinogenesis in ARPE-19 cells. Despite increases in protein levels of Sirtuin 1 and PGC-1α, mitochondrial function was compromised, and this decrease was attributed to disrupted MMP. POS phagocytic activities decreased by 60% in NaIO3-treated cells, and the degradation of ingested POS was also impaired. Pretreatment and cotreatment with rapamycin partially rescued NaIO3-induced RPE dysfunction. CONCLUSIONS: Low concentrations of NaIO3 disrupted the mitochondrial-lysosomal axis in RPE and led to impaired phagocytic activities and degradation capacities.
Assuntos
Iodatos/farmacologia , Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Iodatos/administração & dosagem , Iodatos/química , Lisossomos/metabolismo , Mitocôndrias/metabolismoRESUMO
The aim of this study was to examine the effects of various levels of supplemental calcium iodate (CI) on productive performance, egg quality, blood indices and iodine (I) accumulation in the eggs in commercial laying hens. A total of 240 White Leghorn layers (Hy-line W36) were divided through a completely randomized design into six treatments with five replicates and eight hens per each at 32 weeks of age. This experiment lasted for 12 weeks. Concentrations of I in the mash diets were 0.74, 3.13, 5.57, 8.11, 10.65 and 12.94 mg I/kg of feed in treatments 1-6 respectively. The added doses of CI were included 0.0 (control), 2.5, 5.0, 7.5, 10.0 and 12.5 mg/kg of diet for treatments 1-6 respectively. There were no significant differences in productive performance among the treatments. The highest eggshell strength was observed in group fed diet containing 3.13 mg I/kg (p = .014). The highest percentage of calcium and lowest percentage of phosphorus in eggshell were observed in group fed diet containing 12.94 mg I/kg (p = .0001). Feeding hens with diet containing 12.94 mg I/kg increased serum triiodothyronine-to-thyroxine ratio (p = .0001). Serum alanine aminotransferase activity in hens fed diet containing 12.94 mg I/kg was significantly more than control (p = .041). Blood Serum triglycerides in hens fed diet containing 8.11 mg I/kg were significantly higher than control (p = .0001). Edible fraction of the eggs of birds fed diet containing 12.94 mg I/kg was enriched by I almost 3 times more than those fed diet containing 0.74 mg I/kg. The results suggested that egg production, egg mass, feed intake and feed conversion ratio were not significantly affected by dietary I levels. Iodine accumulation in the eggs were increased by increasing dietary I levels and the level of 10 mg/kg CI could supply I enrichment of the eggs.
Assuntos
Ração Animal/análise , Cálcio da Dieta/farmacologia , Galinhas/fisiologia , Dieta/veterinária , Ovos/normas , Iodatos/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cálcio da Dieta/análise , Suplementos Nutricionais , Casca de Ovo , Feminino , Iodo , Oviposição/efeitos dos fármacosRESUMO
Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory.Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function.Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18-55 y.Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function.Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.
Assuntos
Atenção/efeitos dos fármacos , Compostos Ferrosos/administração & dosagem , Iodatos/administração & dosagem , Percepção/efeitos dos fármacos , Compostos de Potássio/administração & dosagem , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/química , Adolescente , Adulto , Suplementos Nutricionais , Feminino , Alimentos Fortificados , Humanos , Índia , Pessoa de Meia-Idade , Adulto JovemRESUMO
In most studies, the major supplement docosahexaenoic acid (DHA) is administered orally or intraperitoneally. In this study, we proposed to assess the safety and efficacy of the intravitreal injection of DHA in an age-related macular degeneration (AMD) rat model. Different concentrations of DHA were injected into the vitreous body. Histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis showed that there was no difference in thickness, observable structure, or apoptosis among the untreated, normal saline, and DHA groups (0.2, 1.0, 5.0 and 10µg). However, GFAP expression was increased in the 10µg group. To investigate whether intravitreal injection of DHA could protect photoreceptors, we developed a NaIO3-induced retinal damage model in adult rats. Decreases in deformation and thickness were observed in the outer nuclear layer (ONL) after NaIO3 administration but were improved with DHA injection. The NaIO3 group showed a substantial reduction in the number of nuclei in ONL, whereas the DHA group showed an increase. Additionally, significant increases in SOD activity and Nrf2 expression were observed after DHA injection; GFAP and NF-κB expression levels were markedly decreased by DHA injection. Moreover, Western blotting showed that Bax, cleaved caspase-3 and CHOP were notably increased in the NaIO3 group but were significantly decreased by DHA injection. Collectively, intravitreal injection of DHA is safe and effective in select doses in a NaIO3-induced AMD rat model. The current results suggest that intravitreal injection of DHA may be a new avenue for the treatment of AMD.
Assuntos
Apoptose/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Gliose/tratamento farmacológico , Inflamação/tratamento farmacológico , Iodatos/farmacologia , Degeneração Macular/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Células Fotorreceptoras/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/efeitos adversos , Feminino , Gliose/induzido quimicamente , Injeções Intravítreas , Iodatos/administração & dosagem , Degeneração Macular/induzido quimicamente , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Iodine deficiency is an environmental health problem affecting one-third of the global population. An iodine biofortification hydroponic experiment was conducted to explore the iodide and iodate uptake characteristics of strawberry plants, to measure the dosage effects of iodine on plant growth and to evaluate the influence of I- or IO3- application on fruit quality. RESULTS: After biofortification, the iodine contents of the fresh strawberry fruits were 600-4000 µg kg-1 , covering the WHO dietary iodine allowance of 150 µg · day-1 for adults. The iodine uptake of the strawberry plants increased with increasing I- or IO3- concentration of the culture solution. At the same iodine concentration, the iodate uptakes of various plant organs under I- treatments were apparently more than those under IO3- treatments. Low-level exogenous iodine (I- ≤ 0.25 mg L-1 or IO3- ≤ 0.50 mg L-1 ) not only promoted plant growth and increased biomass per plant, but also improved fruit quality by enhancing the vitamin C and soluble sugar contents of the strawberry fruits. Nevertheless, excessive exogenous iodine inhibited plant growth and reduced biomass per plant. IO3- uptake apparently increased the total acidity and nitrate content of the fruits, reducing the quality of the strawberry fruits. Conversely, I- uptake obviously decreased the total acidity and nitrate content of the strawberry fruits, improving the fruit quality. CONCLUSION: The strawberry can be used as a target crop for iodine biofortification. Furthermore, applying an appropriate dose of KI can improve the fruit quality of the strawberry plants. © 2016 Society of Chemical Industry.
Assuntos
Fragaria/crescimento & desenvolvimento , Frutas/química , Frutas/crescimento & desenvolvimento , Iodatos/administração & dosagem , Iodetos/administração & dosagem , Biomassa , Relação Dose-Resposta a Droga , Qualidade dos Alimentos , Alimentos Fortificados , Fragaria/efeitos dos fármacos , Fragaria/metabolismo , Frutas/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Hidroponia , Iodatos/metabolismo , Iodetos/metabolismo , Iodo/administração & dosagem , Iodo/efeitos adversos , Nitratos/análise , Recomendações NutricionaisRESUMO
Excess fluoride and iodide coexist in drinking water in many regions, but few studies have investigated the single or interactive effects on thyroid in vivo. In our study, Wistar rats were exposed to excess fluoride and/or iodide through drinking water for 2 or 8 months. The structure and function of the thyroid, cells apoptosis and the expression of inositol-requiring enzyme 1 (IRE1) pathway-related factors were analyzed. Results demonstrated that excess fluoride and/or iodide could change thyroid follicular morphology and alter thyroid hormone levels in rats. After 8 months treatment, both single and co-exposure of the two microelements could raise the thyroid cells apoptosis. However, the expressions of IRE1-related factors were only increased in fluoride-alone and the combined groups. In conclusion, thyroid structure and thyroid function were both affected by excess fluoride and/or iodide. IRE1-induced apoptosis were involved in this cytotoxic process caused by fluoride or the combination of two microelements.
Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Iodatos/toxicidade , Compostos de Potássio/toxicidade , Fluoreto de Sódio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Iodatos/administração & dosagem , Proteínas de Membrana/metabolismo , Compostos de Potássio/administração & dosagem , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Wistar , Fluoreto de Sódio/administração & dosagem , Testes de Função Tireóidea , Glândula Tireoide/metabolismo , Glândula Tireoide/patologiaRESUMO
PURPOSE: Our purpose was to evaluate the anatomical and functional changes in retinae of rabbit eyes following monocular intravitreal injection of sodium iodate (SI). METHODS: Twenty albino rabbits were divided into four groups and underwent monocular intravitreal injection with four different doses of SI (0.1, 0.2, 0.4, and 0.8 mg). Before and for 28 days after injection, the eyes were examined using fundus photography, optical coherence tomography (OCT), and electroretinography (ERG). At postinjection days 2, 7, and 28, the eyes were enucleated and underwent histological examination. RESULTS: On fundus examination, no distinct retinal changes were seen in any group except the 0.8-mg group, which showed chorioretinal vascular attenuation. In 0.1 and 0.2-mg groups, no significant anatomical changes were found except transient hyperreflective dots over the vitreoretinal interface on OCT. In 0.4 and 0.8-mg groups, disruption of the ellipsoid zone and diffuse retinal swelling were observed in the early period on OCT. In the 0.4-mg group, the outer retina was significantly destroyed at day 28, whereas the inner retina was relatively preserved. In the 0.8-mg group, the entire retina was destroyed irreversibly. The b-wave of ERG was reduced immediately in all groups, which recovered fully (0.1- and 0.2-mg groups), partially (0.4-mg group), or never (0.8-mg group). No structural or functional abnormalities were found in the fellow control eyes. CONCLUSIONS: Retinal degeneration following intravitreal injection of SI appears to be dose dependent; retinal damage is reversible at low doses but irreversible at high doses. At a certain dose, the outer retina may be preferably ablated.
Assuntos
Iodatos/toxicidade , Retina/diagnóstico por imagem , Degeneração Retiniana/diagnóstico , Corpo Vítreo/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Eletrorretinografia , Feminino , Injeções Intravítreas , Iodatos/administração & dosagem , Coelhos , Retina/fisiopatologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/fisiopatologia , Tomografia de Coerência ÓpticaRESUMO
Caveolin-1 (Cav-1), the scaffolding protein of caveolae, is expressed in several retinal cell types and is associated with ocular pathologies. Cav-1 modulates neuroinflammatory/neuroprotective responses to central nervous system injury. We have shown that loss of Cav-1 results in a blunted cytokine response in retinas challenged with inflammatory stimuli. As neuroinflammatory and neuroprotective signaling overlap in their cytokine production and downstream signaling pathways, we hypothesized that loss of Cav-1 may also suppress neuroprotective signaling in the retina. To test this, we subjected mice in which Cav-1 was deleted specifically in the retina to a neurodegenerative insult induced by sodium iodate (NaIO3) and measured STAT3 activation, a measure of neuroprotective signaling. Our results show that Cav-1 ablation blunts STAT3 activation induced by NaIO3. STAT3 activation in response to intravitreal administration of the IL-6 family cytokine, leukemia inhibitory factor (LIF), was not affected by Cav-1 deletion indicating a competent gp130 receptor response. Thus, Cav-1 modulates neuroprotective signaling by regulating the endogenous production of neuroprotective factors.
Assuntos
Caveolina 1/genética , Neuroproteção/genética , Retina/metabolismo , Transdução de Sinais/genética , Animais , Western Blotting , Caveolina 1/deficiência , Feminino , Imuno-Histoquímica , Injeções Intraperitoneais , Iodatos/administração & dosagem , Iodatos/farmacologia , Fator Inibidor de Leucemia/administração & dosagem , Fator Inibidor de Leucemia/farmacologia , Masculino , Camundongos , Camundongos Knockout , Neuroproteção/efeitos dos fármacos , Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Poor iron status affects 50% of Indian women and compromises work productivity, cognitive performance, and reproduction. Among the many strategies to reduce iron deficiency is the commercial fortification of iodized table salt with iron to produce a double-fortified salt (DFS). The objective of this study was to test the efficacy of DFS in reducing iron deficiency in rural women of reproductive age from northern West Bengal, India. The participants were 212 women between 18 and 55 y of age who worked as full-time tea pickers on a large tea estate. Participants in the randomized, controlled, double-blind study were assigned to use either DFS or a control iodized salt for 7.5 to 9 mo. The DFS was fortified with 3.3-mg ferrous fumarate (1.1-mg elemental iron) per kg of iodized salt, whereas the control salt contained only iodine (47 mg/kg potassium iodate), and both salt varieties were distributed gratis to the families of participants at 0.5 kg/mo for each 2 household members. At baseline, 53% of participants were anemic (hemoglobin <120 g/L), 25% were iron deficient (serum ferritin <12 µg/L), and 23% were iron-deficient anemic. Also, 22% had a transferrin receptor concentration >8.6 mg/L and 22% had negative (<0.0 mg/kg) body iron stores. After 9 mo the participants receiving DFS showed significant improvements compared with controls in hemoglobin (+2.4 g/L), ferritin (+0.13 log10 µg/L), soluble transferrin receptor (-0.59 mg/L), and body iron (+1.43 mg/kg), with change in status analyzed by general linear models controlling for baseline values. This study demonstrated that DFS is an efficacious approach to improving iron status and should be further evaluated for effectiveness in the general population. This trial was registered at clinicaltrials.gov as NCT01032005.
Assuntos
Anemia Ferropriva/epidemiologia , Alimentos Fortificados , Iodo/administração & dosagem , Cloreto de Sódio na Dieta/administração & dosagem , População Branca , Adolescente , Adulto , Anemia Ferropriva/prevenção & controle , Antropometria , Método Duplo-Cego , Feminino , Ferritinas/sangue , Compostos Ferrosos/administração & dosagem , Seguimentos , Hemoglobinas/metabolismo , Humanos , Índia/epidemiologia , Iodatos/administração & dosagem , Iodo/química , Ferro da Dieta/sangue , Modelos Lineares , Pessoa de Meia-Idade , Compostos de Potássio/administração & dosagem , Receptores da Transferrina/sangue , Adulto JovemRESUMO
PURPOSE: The objective of this study was to investigate the influence of high dietary iodine supply and different iodine sources on thyroid status and oxidative stress in target tissues of the thyroid hormones in fattening pigs. METHODS: Eighty castrates (body weight: 33.3 ± 0.4 kg) were randomly allotted into five different treatments: The control diet contained 150 µg I/kg as KI, the other feeding groups were supplemented with 4,000 µg I/kg (as KI and KIO(3)) and 10,000 µg I/kg (as KI and KIO(3)), respectively. The mRNA expression levels of sodium/iodide symporter (NIS) and key antioxidant enzymes (Cu/Zn SOD, CAT, GPx) were analyzed in thyroid gland, liver, kidney, muscle, and adipose tissue sampled during slaughter. Furthermore, antioxidant enzyme activities and the effect on lipid peroxidation (MDA) were determined in liver and muscle. RESULTS: In thyroid gland, a significant downregulation of NIS and Cu/Zn SOD mRNA expression was observed in high-iodine groups. In liver, a source effect on the mRNA expression of Cu/Zn SOD between KI and KIO(3) at 4,000 µg I/kg was shown. In contrast, not SOD but GPx activity was affected by iodine source with strongest downregulation in high KIO(3) group. In muscle, GPx activity was affected by both iodine source and dose, showing stronger downregulation in KI groups. In kidney and adipose tissue, oxidative stress parameters showed no or only unsystematic changes. However, variation in iodine supply had no effect on MDA concentrations. CONCLUSIONS: NIS expression was significantly decreased with increased iodine supplementation, which is to ensure the thyroid gland function. However, the alleviating effect of iodine supplementation observed in antioxidant enzyme mRNA expression and activity did not reflect on the lipid peroxide level.
Assuntos
Antioxidantes/metabolismo , Suplementos Nutricionais , Iodatos/administração & dosagem , Iodetos/administração & dosagem , Iodo/administração & dosagem , RNA Mensageiro/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Regulação para Baixo , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/análise , Peróxidos Lipídicos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Suínos , Simportadores/genética , Simportadores/metabolismo , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismoRESUMO
Sodium iodate (NaIO(3))-induced retina injury is one of models that is commonly used to study various retinal diseases caused by retinal pigment epithelium (RPE) injury such as AMD. Previous researches have revealed that RPE and photoreceptors are main impaired objects in this model. By comparison, intra-retinal layer has not been studied in detail after NaIO(3) administration. In this study, we present evidences that intra-retinal neurons can be directly injured by NaIO(3) at early stage and that the morphology had taken obvious changes, the decreased areas of dendritic fields of dopaminergic amacrine cells (DA-ACs), horizontal cells, and melanopsin-expressing retinal ganglion cells (mRGCs). Moreover, we found that miRNA 133b that was considered specifically to express in midbrain dopaminergic neurons was markedly upregulated in retinal DA-ACs after NaIO(3) administration. The overexpression of mir-133b negatively regulated the expression of pitx3, an important transcription factor, and led to a series of deficits of DA-ACs such as TH and D2 receptor expression and DA producing, which may play a causative role in pathological events of horizontal cells and mRGCs. After mir-133b was interfered with mir-133b/RNAi, not only those deficits were rescued, but also the amplitude of b-wave and summed OPs of ERG were improved significantly. In conclusion, our data demonstrate, for the first time, that intra-retinal neurons can be directly injured by NaIO(3) at early stage, and that mir-133b level effectively controls synaptic contacts or neural interactions among DA-ACs, horizontal cells, and mRGCs. Delivering mir-133b/RNAi intravitreally can rescue NaIO(3)-induced failure and improve visual function by restoring synaptic contacts.
Assuntos
Células Amácrinas/metabolismo , Dopamina/metabolismo , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo , Células Amácrinas/patologia , Animais , Eletrorretinografia , Glutamato Descarboxilase/metabolismo , Iodatos/administração & dosagem , Mesencéfalo/patologia , MicroRNAs/metabolismo , Interferência de RNA , Ratos , Degeneração Retiniana/fisiopatologia , Células Ganglionares da Retina/patologia , Transdução de SinaisRESUMO
In the presented study the effect of different iodine (I) levels and sources in hen feed on the iodine concentration of different tissues, blood serum, and eggs of laying hens was studied. For this purpose, two experiments were conducted with 30 laying hens each. In these experiments feed was enriched with KI and Ca(IO(3))(2), respectively, at 0 (Control), 0.25, 0.5, 2.5 and 5 mg I/kg feed, resulting a analysed iodine level from 0.44 to 4.20 mg/kg feed. After four weeks experimental feeding the iodine concentrations of thyroid glands, blood, meat, liver, abdominal fat and eggs were measured with inductively coupled plasma mass spectrometry. The experimental treatment did not affect hen performance. The iodine supplementation significantly increased the iodine concentration of eggs (144-1304 µg/kg), thyroid glands (3367-5975 µg/g), blood serum (16-67 µg/kg) and liver (13-43 µg/kg). Meat (about 14 µg I/kg) and abdominal fat (about 12 µg I/kg) were not significantly affected by iodine treatment. Comparative regression analyses showed that at a similar iodine intake, the supply via KI resulted in significantly higher iodine deposition into eggs than Ca(IO(3))(2). Due to the high carry-over of iodine into eggs, eggs may considerably contribute to the iodine supply of the consumers.
Assuntos
Galinhas/metabolismo , Ovos/análise , Iodo/farmacologia , Músculo Esquelético/química , Glândula Tireoide/química , Gordura Abdominal , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cálcio/administração & dosagem , Cálcio/metabolismo , Cálcio/farmacologia , Dieta/veterinária , Relação Dose-Resposta a Droga , Feminino , Iodatos/administração & dosagem , Iodatos/metabolismo , Iodatos/farmacologia , Iodo/administração & dosagem , Iodo/química , Iodo/metabolismo , Carne , Músculo Esquelético/metabolismo , Oviposição , Iodeto de Potássio/administração & dosagem , Iodeto de Potássio/metabolismo , Iodeto de Potássio/farmacologia , Glândula Tireoide/metabolismoRESUMO
BACKGROUND: Food fortification began in Ghana in 1996 when legislation was passed to enforce the iodization of salt. This paper describes the development of the Ghanaian fortification program and identifies lessons learned in implementing fortification initiatives (universal salt iodization, fortification of vegetable oil and wheat flour) from 1996 to date. OBJECTIVE: This paper identifies achievements, challenges, and lessons learned in implementing large scale food fortification in Ghana. METHODOLOGY: Primary data was collected through interviews with key members of the National Food Fortification Alliance (NFFA), implementation staff of the Food Fortification Project, and staff of GAIN. Secondary data was collected through desk review of documentation from the project offices of the National Food Fortification Project and the National Secretariat for the Implementation of the National Salt Iodization in Ghana. RESULTS: Reduction of the prevalence of goiter has been observed, and coverage of households with adequately iodized salt increased between 1996 and 2006. Two models were designed to increase production of adequately iodized salt: one to procure and distribute potassium iodate (KIO3) locally, and the second, the salt bank cooperative (SBC) model, specifically designed for small-scale artisanal salt farmers. This resulted in the establishment of a centralized potassium iodate procurement and distribution system, tailored to local needs and ensuring competitive and stable prices. The SBC model allowed for nearly 157 MT of adequately iodized salt to be produced in 2011 in a region where adequately iodized salt was initially not available. For vegetable oil fortification, implementing quantitative analysis methods for accurate control of added fortificant proved challenging but was overcome with the use of a rapid test device, confirming that 95% of vegetable oil is adequately fortified in Ghana. However, appropriate compliance with national standards on wheat flour continues to pose challenges due to adverse sensory effects, which have led producers to reduce the dosage of premix in wheat flour. CONCLUSIONS: Challenges to access to premix experienced by small producers can be overcome with a central procurement model in which the distributor leverages the overall volume by tendering for a consolidated order. The SBC model has the potential to be expanded and to considerably increase the coverage of the population consuming iodized salt in Ghana. Successful implementation of the cost-effective iCheck CHROMA rapid test device should be replicated in other countries where quality control of fortified vegetable oil is a challenge, and extended to additional food vehicles, such as wheat flour and salt. Only a reduced impact on iron deficiency in Ghana can be expected, given the low level of fortificant added to the wheat flour. An integrated approach, with complementary programs including additional iron-fortified food vehicles, should be explored to maximize health impact.