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1.
Curr Pharm Des ; 25(15): 1707-1716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31267853

RESUMO

Selenium is an essential non-metal trace element, and the imbalance in the bioavailability of selenium is associated with many diseases ranking from acute respiratory distress syndrome, myocardial infarction and renal failure (Se overloading) to diseases associated with chronic inflammation like inflammatory bowel diseases, rheumatoid arthritis, and atherosclerosis (Se unload). The only source of selenium is the diet (animal and cereal sources) and its intestinal absorption is limiting for selenocysteine and selenomethionine synthesis and incorporation in selenoproteins. In this review, after establishing the link between selenium and inflammatory diseases, we envisaged the potential of selenium nanoparticles and organic selenocompounds to compensate the deficit of selenium intake from the diet. With high selenium loading, nanoparticles offer a low dosage to restore selenium bioavailability whereas organic selenocompounds can play a role in the modulation of their antioxidant or antiinflammatory activities.


Assuntos
Inflamação/terapia , Selênio/farmacologia , Oligoelementos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Disponibilidade Biológica , Dieta , Humanos , Nanopartículas , Selênio/administração & dosagem , Selenocisteína , Selenometionina , Selenoproteínas , Oligoelementos/administração & dosagem
2.
Mar Drugs ; 17(5)2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31083588

RESUMO

Refractory wound healing is one of the most common complications of diabetes. Excessive production of reactive oxygen species (ROS) can cause chronic inflammation and thus impair cutaneous wound healing. Scavenging these ROS in wound dressing may offer effective treatment for chronic wounds. Here, a nanocomposite hydrogel based on alginate and positively charged Eudragit nanoparticles containing edaravone, an efficient free radical scavenger, was developed for maximal ROS sequestration. Eudragit nanoparticles enhanced edaravone solubility and stability breaking the limitations in application. Furthermore, loading these Eudragit nanoparticles into an alginate hydrogel increased the protection and sustained the release of edaravone. The nanocomposite hydrogel is shown to promote wound healing in a dose-dependent way. A low dose of edaravone-loaded nanocomposite hydrogel accelerated wound healing in diabetic mice. On the contrary, a high dose of edaravone might hamper the healing. Those results indicated the dual role of ROS in chronic wounds. In addition, the discovery of this work pointed out that dose could be the key factor limiting the translational application of antioxidants in wound healing.


Assuntos
Alginatos/administração & dosagem , Hidrogéis/administração & dosagem , Nanocompostos/administração & dosagem , Nanopartículas/administração & dosagem , Cicatrização/efeitos dos fármacos , Alginatos/química , Animais , Materiais Biocompatíveis/administração & dosagem , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Hidrogéis/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanocompostos/química , Nanopartículas/química , Distribuição Aleatória , Espécies Reativas de Oxigênio/metabolismo
3.
C R Biol ; 338(2): 95-102, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25543885

RESUMO

Hemoglobin-based oxygen carriers (HBOCs) may generate oxidative stress, vasoconstriction and inflammation. To reduce these undesirable vasoactive properties, we increased hemoglobin (Hb) molecular size by genetic engineering with octameric Hb, recombinant (r) HbßG83C. We investigate the potential side effects of rHbßG83C on endothelial cells. The rHbßG83C has no impact on cell viability, and induces a huge repression of endothelial nitric oxide synthase gene transcription, a marker of vasomotion. No induction of Intermolecular-Adhesion Molecule 1 and E-selectin (inflammatory markers) transcription was seen. In the presence of rHbßG83C, the transcription of heme oxygenase-1 (oxidative stress marker) is weakly increased compared to the two other HBOCs (references) or Voluven (control). This genetically engineered octameric Hb, based on a human Hb ßG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development.


Assuntos
Substitutos Sanguíneos/farmacologia , Hemoglobinas/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Biomarcadores , Substitutos Sanguíneos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Dextranos/farmacologia , Dextranos/toxicidade , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Selectina E/biossíntese , Selectina E/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/biossíntese , Heme Oxigenase-1/genética , Hemoglobinas/análise , Hemoglobinas/química , Hemoglobinas/toxicidade , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/toxicidade , Inflamação/induzido quimicamente , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/genética , Metemoglobina/análise , Modelos Moleculares , Óxido Nítrico Sintase Tipo III/biossíntese , Óxido Nítrico Sintase Tipo III/genética , Estresse Oxidativo/efeitos dos fármacos , Substitutos do Plasma/farmacologia , Substitutos do Plasma/toxicidade , Conformação Proteica , Reação em Cadeia da Polimerase em Tempo Real , Vasoconstrição/efeitos dos fármacos
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