RESUMEN
The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 109 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens.
Asunto(s)
Suplementos Dietéticos , Sustancias Húmicas , Enfermedades de las Aves de Corral , Salmonelosis Animal , Compuestos de Selenio , Compuestos de Zinc , Pollos/microbiología , Citocinas/metabolismo , Heces/microbiología , Gastroenteritis/tratamiento farmacológico , Crecimiento/efectos de los fármacos , Intestinos/efectos de los fármacos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/prevención & control , Salmonelosis Animal/tratamiento farmacológico , Salmonelosis Animal/prevención & control , Salmonella typhimurium , Compuestos de Selenio/farmacología , Compuestos de Selenio/uso terapéutico , Transducción de Señal/efectos de los fármacos , Compuestos de Zinc/farmacología , Compuestos de Zinc/uso terapéutico , AnimalesRESUMEN
Selenium has good antitumor effects in vitro, but the hypoxic microenvironment in solid tumors makes its clinical efficacy unsatisfactory. We hypothesized that the combination with oxygen therapy might improve the treatment efficacy of selenium in hypoxic tumors through the changes of redox environment. In this work, two selenium compounds, Na2SeO3 and CysSeSeCys, were selected to interrogate their therapeutic effects on hepatocellular carcinoma (HCC) under different oxygen levels. In tumor-bearing mice, both selenium compounds significantly inhibited the tumor growth, and combined with oxygen therapy further reduced the tumor volume about 50 %. In vitro HepG2 cell experiments, selenium induced autophagy and delayed apoptosis under hypoxia (1 % O2), while inhibited autophagy and accelerated apoptosis under hyperoxia (60 % O2). We found that, in contrast to hypoxia, the hyperoxic environment facilitated the H2Se, produced by the selenium metabolism in cells, to be rapidly oxidized to generate H2O2, leading to inhibit the expression level of Nrf2 and to increase that of phosphorylation of p38 and MKK4, resulting in inhibiting autophagy and accelerating apoptosis. Once the Nrf2 gene was knocked down, selenium compounds combined with hyperoxia treatment would further activate the MAPK signaling pathway and further increase apoptosis. These findings highlight oxygen can significantly enhance the anti-HCC effect of selenium compounds through regulating the Nrf2 and MAPK signaling pathways, thus providing novel therapeutic strategy for the hypoxic tumors and pave the way for the application of selenium in clinical treatment.
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Carcinoma Hepatocelular , Hiperoxia , Neoplasias Hepáticas , Compuestos de Selenio , Selenio , Animales , Ratones , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Selenio/farmacología , Selenio/uso terapéutico , Compuestos de Selenio/metabolismo , Compuestos de Selenio/farmacología , Compuestos de Selenio/uso terapéutico , Peróxido de Hidrógeno/farmacología , Transducción de Señal , Apoptosis , Hipoxia , Oxígeno , Microambiente TumoralRESUMEN
BACKGROUND: Alzheimer's disease (AD) is one of the most prevalent types of dementia, affecting millions of older people worldwide. AD is stimulating efforts to develop novel molecules targeting its main features associated with a decrease in acetylcholine levels, an increase in oxidative stress and depositions of amyloid-ß (Aß) and tau protein. In this regard, selenium-containing compounds have been demonstrated as potential multi-targeted compounds in the treatment of AD. These compounds are known for their antioxidant and anticholinesterase properties, causing a decrease in Aß aggregation. OBJECTIVE: In this review, we approach structure-activity relationships of each compound, associating the decrease of ROS activity, an increase of tau-like activity and inhibition of AChE with a decrease in the self-aggregation of Aß. METHODS: We also verify that the molecular descriptors apol, nHBAcc and MlogP may be related to optimized pharmacokinetic properties for anti-AD drugs. RESULTS: In our analysis, few selenium-derived compounds presented similar molecular features to FDA-approved drugs. CONCLUSION: We suggest that unknown selenium-derived molecules with apol, nHBAcc and MlogP like FDA-approved drugs may be better successes with optimized pharmacokinetic properties in future studies in AD.
Asunto(s)
Enfermedad de Alzheimer , Compuestos de Selenio , Selenio , Humanos , Anciano , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Selenio/uso terapéutico , Compuestos de Selenio/uso terapéutico , Péptidos beta-Amiloides/metabolismo , Estrés OxidativoRESUMEN
Selenium compounds have pronounced effects on cell growth and proliferation. Nutritional levels induce selenoproteins. However, the antineoplastic effects of supra-nutritional selenium levels are not mediated by selenoproteins. The most studied compound, selenite, was shown in a clinical trial to possess extraordinary pharmacological properties. The uptake of selenite as for GS-Se-SG and selenocystine is dependent on the extracellular reducing environment maintained by the Xc- cystine transporter (xc- antiporter) ensuring a high level of extracellular cysteine. The expression of the xc- antiporter is vital for selenium cytotoxicity and any xenobiotic or media constituents modulating the expression of this antiporter will greatly affect the cellular response. Cytotoxicity determinations are often difficult to interpret and repeat due to differences in culture conditions. In the current chapter, factors influencing the cellular response, e.g., media composition, cell culturing conditions, assays for key enzymes of importance for selenium metabolism and effects, along with selenium mediated modulation of microRNA expression and immune responses are treated.
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Neoplasias , Compuestos de Selenio , Selenio , Cisteína/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Selenio/metabolismo , Selenio/farmacología , Selenio/uso terapéutico , Compuestos de Selenio/metabolismo , Compuestos de Selenio/farmacología , Compuestos de Selenio/uso terapéutico , SelenoproteínasRESUMEN
Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.
Asunto(s)
Neoplasias de la Mama/terapia , Hipertermia Inducida , Nanopartículas de Magnetita/uso terapéutico , Nanocápsulas/uso terapéutico , Compuestos de Selenio/uso terapéutico , Animales , Neoplasias de la Mama/patología , Carcinoma de Ehrlich/patología , Carcinoma de Ehrlich/terapia , Ciclo Celular/efectos de los fármacos , Terapia Combinada , Fragmentación del ADN/efectos de los fármacos , Femenino , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestructura , Ratones , Nanocápsulas/química , Nanocápsulas/ultraestructura , Compuestos de Selenio/química , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe-/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed.
Asunto(s)
Compuestos de Selenio/farmacología , Compuestos de Selenio/uso terapéutico , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Técnicas de Química Sintética , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Compuestos de Selenio/síntesis química , Compuestos de Selenio/química , Selenoproteínas/genética , Sodio/química , Selenito de Sodio/químicaRESUMEN
We studied immunotropic properties of synthetic selenium-organic preparation 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonyl dibromide (974zh). The experimental preparation reduced the cAMP/cGMP ratio, which indicated an increase in proliferative activity of cells of immunocompetent organs (thymus and spleen) in experimental animals. It was shown that 974zh intensified the immune response to Yersinia pestis EV thereby increasing the resistance to the plague agent.
Asunto(s)
Inmunidad Innata/efectos de los fármacos , Compuestos de Selenio/farmacología , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Animales , Terapia Combinada , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Femenino , Masculino , Ratones , Compuestos Orgánicos/química , Compuestos Orgánicos/farmacología , Compuestos Orgánicos/uso terapéutico , Peste/tratamiento farmacológico , Peste/inmunología , Peste/prevención & control , Vacuna contra la Peste/administración & dosificación , Selenio/química , Selenio/farmacología , Selenio/uso terapéutico , Compuestos de Selenio/química , Compuestos de Selenio/uso terapéutico , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismo , Timo/efectos de los fármacos , Timo/inmunología , Timo/metabolismo , Potencia de la Vacuna , Virulencia/efectos de los fármacos , Yersinia pestis/efectos de los fármacos , Yersinia pestis/inmunología , Yersinia pestis/patogenicidadRESUMEN
BACKGROUND: This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer. OBJECTIVES: To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer. DATA COLLECTION AND ANALYSIS: Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach. MAIN RESULTS: In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.
Asunto(s)
Suplementos Dietéticos , Estado de Salud , Neoplasias Pulmonares/prevención & control , Minerales/uso terapéutico , Vitaminas/uso terapéutico , Ácido Ascórbico/uso terapéutico , Calcio de la Dieta/efectos adversos , Calcio de la Dieta/uso terapéutico , Colecalciferol/uso terapéutico , Intervalos de Confianza , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/mortalidad , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Selenio , Compuestos de Selenio/uso terapéutico , Factores Sexuales , Vitamina A/efectos adversos , Vitamina A/uso terapéutico , Vitamina E/uso terapéutico , Vitaminas/efectos adversos , alfa-Tocoferol/efectos adversos , alfa-Tocoferol/uso terapéutico , beta Caroteno/uso terapéuticoRESUMEN
3-(4-Chlorophenylselanyl)-1-methyl-1H-indole (CMI) is an organoselenium compound that presents antioxidant activity, antinociceptive, anti-inflammatory and antidepressive-like effect in mice in previous studies conducted by our research group. In this study, we evaluate the anti-allodynic, anti-hyperalgesic and antidepressant-like effects of CMI on partial sciatic nerve ligation (PSNL) in male adult Swiss mice (25-35 g) as well as the involvement of oxidative stress in these effects. Mice underwent PSNL surgery and after 4 weeks they were treated with CMI (10 mg/kg, intragastric route [i.g.]) or vehicle. The treatment with CMI (10 mg/kg, i.g.) reversed the increased the percentage of response to Von-Frey Hair (VFH) stimulation, decreased the latency time to nociceptive response in the hot-plate test, increased immobility time in the forced swimming test (FST) and decreased groomings activity in the splash test, all induced by PSNL. Additionally, CMI also reversed increased the levels of reactive oxygen species (ROS) and lipid peroxidation in cortex and hippocampus and plasmatic levels of corticosterone in mice, induced by PSNL. Results demonstrate that CMI reversed behavioral and biochemical alterations in the dyad pain-depression induced by PSNL and possibly modulation of oxidative system.
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Indoles/uso terapéutico , Neuralgia/sangre , Neuralgia/tratamiento farmacológico , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiopatología , Compuestos de Selenio/uso terapéutico , Animales , Antiinflamatorios/uso terapéutico , Antidepresivos/uso terapéutico , Antioxidantes/uso terapéutico , Corticosterona , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Neuralgia/fisiopatología , Especies Reactivas de Oxígeno/sangre , Selenio/sangre , Natación/fisiologíaRESUMEN
OBJECTIVE: To compare the effectiveness of five kinds of selenium supplementation for the treatment of patients with Kashin-Beck disease, and rank these selenium supplementations based on their performance. DESIGN: We searched for all publications between 1 January 1966 and 31 March 2017 using seven electronic databases. GRADE system to network meta-analyses (NMAs) was applied to rate the quality of the evidence. We conducted a random effects model NMA in STATA 12.1 to determine comparative effectiveness of each intervention. Rankings were obtained by using the surface under the cumulative ranking curve (SUCRA) values and mean ranks. RESULTS: A total of 15 randomised controlled trials involving 2931 patients were included. After assessment of the overall quality of the evidence, we downgraded our primary outcomes from high to low or very low quality. NMAs showed that all five kinds of selenium supplementation had higher metaphysis X-ray improvement which were superior to placebo. Ranking on efficacy indicated that selenium salt was ranked the highest, followed by sodium selenite + vitamin E, selenium enriched yeast, sodium selenite and then sodium selenite + vitamin C. CONCLUSIONS: Based on the results of NMA, all five types of selenium supplements are more effective than placebo and so that selenium supplementation is of help in repairing metaphyseal lesions. Since the overall quality of the evidence was low or very low, the SUCRA values may be misleading and should be considered jointly with the The Grading of Recommendations Assessment, Development and Evaluation (GRADE) confidence in the estimates for each comparison. The quality of the evidence is insufficient to draw a conclusion about what method of selenium supplementation is most effective. PROSPERO REGISTRATION NUMBER: CRD42016051874.
Asunto(s)
Huesos/efectos de los fármacos , Suplementos Dietéticos , Enfermedad de Kashin-Beck/tratamiento farmacológico , Compuestos de Selenio/uso terapéutico , Selenio/uso terapéutico , Adolescente , Huesos/patología , Niño , Preescolar , Femenino , Humanos , Enfermedad de Kashin-Beck/patología , Masculino , Metaanálisis en Red , Radiografía , Selenio/farmacología , Compuestos de Selenio/farmacologíaRESUMEN
Bladder cancer is the most prevalent malignancy of the urinary tract and is associated with significant morbidity and mortality. Preventative efforts to reduce the medical and financial burdens of bladder cancer are highly desirable. However, the utilization of natural and pharmaceutical products for the prevention and treatment of bladder cancer remains largely controversial. Herein, we review the current body of evidence surrounding a number of natural dietary substances and their roles in chemoprevention of bladder cancer. Possible chemopreventative properties of several pharmaceutical agents are also reviewed. Overall, the current body of evidence is insufficient to establish a clear link between these proposed chemopreventive agents and risk of bladder cancer.
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Antineoplásicos/uso terapéutico , Neoplasias de la Vejiga Urinaria/prevención & control , Antiinflamatorios no Esteroideos/uso terapéutico , Quimioprevención , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Metformina/uso terapéutico , Polifenoles/química , Polifenoles/uso terapéutico , Compuestos de Selenio/química , Compuestos de Selenio/uso terapéutico , Neoplasias de la Vejiga Urinaria/patología , Vitaminas/uso terapéuticoRESUMEN
In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of action. The latter includes direct and indirect redox effects on cellular targets by the activation and altered compartmentalization of molecular oxygen, and the interaction with protein thiols and Se proteins. As such, Se compounds interfere with the redox homeostasis and signaling of cancer cells to produce anticancer effects that include alterations in key regulatory elements of energy metabolism and cell cycle checkpoints that ultimately influence differentiation, proliferation, senescence, and death pathways. Cys-containing proteins and Se proteins involved in the response to Se compounds as sensors and transducers of anticancer signals, i.e., the pharmacoproteome of Se compounds, are described and include critical elements in the different phases of cancer onset and progression from initiation and escape of immune surveillance to tumor growth, angiogenesis, and metastasis. The efficacy and mode of action on these compounds vary depending on the inorganic and organic form of Se used as either supplement or pharmacological agent. In this regard, differences in experimental/clinical protocols provide options for either chemoprevention or therapy in different human cancers.
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Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Compuestos de Selenio/farmacología , Compuestos de Selenio/uso terapéutico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Neovascularización Patológica/tratamiento farmacológicoAsunto(s)
Corticoesteroides/uso terapéutico , Antifúngicos/uso terapéutico , Dermatitis Seborreica/terapia , Inhibidores Enzimáticos/uso terapéutico , Queratolíticos/uso terapéutico , Fototerapia , Administración Cutánea , Lesiones Traumáticas del Encéfalo/epidemiología , Inhibidores de la Calcineurina , Dermatitis Seborreica/epidemiología , Dermatitis Seborreica/inmunología , Dermatomicosis/epidemiología , Dieta , Dermatosis Facial , Humanos , Imidazoles/uso terapéutico , Malassezia , Compuestos Organometálicos/uso terapéutico , Enfermedad de Parkinson/epidemiología , Piridinas/uso terapéutico , Factores de Riesgo , Dermatosis del Cuero Cabelludo , Compuestos de Selenio/uso terapéutico , Traumatismos de la Médula Espinal/epidemiologíaRESUMEN
Nanoscale ternary chalcogenides have attracted intense research interest due to their wealth of tunable properties and diverse applications in energy and environmental and biomedical fields. In this article, ultrasmall magnetic CuFeSe2 ternary nanocrystals (<5.0 nm) were fabricated in the presence of thiol-functionalized poly(methacrylic acid) by an environmentally friendly aqueous method under ambient conditions. The small band gap and the existence of intermediate bands lead to a broad NIR absorbance in the range of 500-1100 nm and high photothermal conversion efficiency (82%) of CuFeSe2 nanocrystals. The resultant CuFeSe2 nanocrystals show superparamagnetism and effective attenuation for X-rays. In addition, they also exhibit excellent water solubility, colloidal stability, biocompatibility, and multifunctional groups. These properties enable them to be an ideal nanotheranostic agent for multimodal imaging [e.g., photoacoustic imaging (PAI), magnetic resonance imaging (MRI), computed tomography (CT) imaging] guided photothermal therapy of cancer.
Asunto(s)
Cobre/química , Hierro/química , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Compuestos de Selenio/uso terapéutico , Nanomedicina Teranóstica/métodos , Animales , Línea Celular Tumoral , Hipertermia Inducida/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Ratones Endogámicos BALB C , Imagen Multimodal/métodos , Nanopartículas/química , Técnicas Fotoacústicas/métodos , Fototerapia , Compuestos de Selenio/química , Tomografía Computarizada por Rayos X/métodosRESUMEN
In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.
Asunto(s)
Antineoplásicos/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Técnicas de Transferencia de Gen , Nanopartículas/uso terapéutico , Neoplasias/terapia , Compuestos de Selenio/uso terapéutico , Selenio/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Portadores de Fármacos/uso terapéutico , Terapia Genética/métodos , Humanos , Nanopartículas/administración & dosificación , Nanopartículas/química , Nanotecnología/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/prevención & control , Selenio/administración & dosificación , Selenio/química , Selenio/farmacología , Compuestos de Selenio/administración & dosificación , Compuestos de Selenio/química , Compuestos de Selenio/farmacologíaRESUMEN
Neuroinflammation and oxidative stress are key intertwined pathological factors in many neurological, particularly neurodegenerative diseases, such as Alzheimer's and Parkinson's disorders as well as autism. The present study was conducted to evaluate the protective effects of Selol, an organic selenium donor, against lipopolysaccharide (LPS)-mediated inflammation in rat brain. The results demonstrated that the peripheral administration of LPS in a dose of 100 µg/kg b.w. evoked typical pathological reaction known as systemic inflammatory response. Moreover, we observed elevated blood levels of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, as well as increased concentration of tumor necrosis factor-α (TNF-α) in LPS-treated animals. Selol significantly prevented these LPS-evoked changes. Subsequently, Selol protected against LPS-induced up-regulation of proinflammatory cytokines (Tnfa, Ifng, Il6) in rat brain cortex. The molecular mechanisms through which Selol prevented the neuroinflammation were associated with the inhibition of oxidized glutathione (GSSG) accumulation and with an increase of glutathione-associated enzymes: glutathione peroxidase (Se-GPx), glutathione reductase (GR) as well as thioredoxin reductase (TrxR) activity and expression. Finally, we observed that Selol administration effectively protected against LPS-induced changes in the expression of brain-derived neurotrophic factor (Bdnf). In conclusion, our studies indicated that Selol effectively protects against LPS-induced neuroinflammation by inhibiting pro-inflammatory cytokine release, by boosting antioxidant systems, and by augmenting BDNF level. Therefore, Selol could be a multi-potent and effective drug useful in the treatment and prevention of brain disorders associated with neuroinflammation.
Asunto(s)
Encéfalo/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Estrés Oxidativo/fisiología , Compuestos de Selenio/farmacología , Selenio/metabolismo , Animales , Encéfalo/efectos de los fármacos , Femenino , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Wistar , Compuestos de Selenio/uso terapéuticoRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aß) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aß production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aß plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.
Asunto(s)
Enfermedad de Alzheimer/dietoterapia , Suplementos Dietéticos , Compuestos de Selenio/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Humanos , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Compuestos de Selenio/administración & dosificación , Compuestos de Selenio/metabolismo , Compuestos de Selenio/farmacologíaRESUMEN
Peptidyl prolyl cis/trans isomerization by Pin1 regulates various oncogenic signals during cancer progression, and its inhibition through multiple approaches has established Pin1 as a therapeutic target. However, lack of simplified screening systems has limited the discovery of potent Pin1 inhibitors. We utilized phosphorylation-dependent binding of Pin1 to its specific substrate to develop a screening system for Pin1 inhibitors. Using this system, we screened a chemical library, and identified a novel selenium derivative as Pin1 inhibitor. Based on structure-activity guided chemical synthesis, we developed more potent Pin1 inhibitors that inhibited cancer cell proliferation.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Peptidilprolil Isomerasa de Interacción con NIMA/antagonistas & inhibidores , Neoplasias Experimentales/tratamiento farmacológico , Compuestos de Selenio/química , Compuestos de Selenio/uso terapéutico , Sitios de Unión , Línea Celular Tumoral , Humanos , Neoplasias Experimentales/patología , Unión Proteica , Mapeo de Interacción de Proteínas/métodos , Resultado del TratamientoRESUMEN
Selenium, a "dual-surface" element, maintains a very thin line between a level of necessity and harmfulness. Because of this, a deficiency or excess of this element in an organism is dangerous and causes health-related problems, both physically and mentally. The main source of selenium is a balanced diet, with a proper selection of meat and plant products. Meanwhile, the proper assimilation of selenium into these products depends on their bioavailability, bioaccessibility, and/or bioactivity of a given selenium compound. From the time when it was discovered that selenium and its compounds have a significant influence on metabolic processes and in many countries throughout the world, a low quantity of selenium was found in different parts of the environment, pressure was put upon an effective and fast method of supplementing the environment with the help of selenium. This work describes supplementation methods applied with the use of selenium, as well as new ideas for increasing the level of this element in various organisms. Based on the fact that selenium appears in the environment at trace levels, the determination of total amount of selenium or selenium speciation in a given sample demands the selection of appropriate measurement methods. These methods are most often comprised of a sample preparation technique and/or a separation technique as well as a detection system. The work presents information on the subject of analytical methods used for determining selenium and its compounds as well as examples in literature of their application.