RESUMO
Nonalcoholic fatty liver disease is a complex disorder which includes simple steatosis, steatohepatitis, fibrosis and ultimately cirrhosis. Previous studies have reported that genistein, a soy phytoestrogen, attenuates steatohepatitis induced in obese and type 2 diabetic models. Here we investigated the effect of dietary genistein supplementation (0.05%) on nonalcoholic steatohepatitis (NASH) development induced by a methionine-choline-deficient (MCD) diet in db/db mice. MCD-diet-fed mice exhibited a significantly lower body weight and a higher degree of steatohepatitis with increased oxidative stress, steatosis, inflammation, stellate cell activation, and mild fibrosis. Although genistein did not inhibit hepatic steatosis, we observed that oxidative stress, endoplasmic reticulum stress, and AMP-dependent kinase inactivation were alleviated by genistein. Genistein also down-regulated the augmented gene expressions associated with hepatic inflammation and fibrosis. Therefore, these results suggest that genistein may protect MCD-diet-mediated NASH development by suppressing lipid peroxidation, inflammation, and even liver fibrosis in db/db mice.
Assuntos
Colina/análise , Suplementos Nutricionais/análise , Genisteína/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Fígado/imunologia , Metionina/deficiência , Animais , Dieta/efeitos adversos , Modelos Animais de Doenças , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Masculino , Metionina/análise , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacosRESUMO
The purpose of this study was to fabricate porous poly(lactide-co-glycolide) (PLGA) microparticles for efficient pulmonary deposition and increased therapeutic duration of the antioxidant anthocyanin (ATH). These microparticles were prepared by a water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with vaporizing ammonium bicarbonate (AB) as a porogen and starch as a viscous additive. High porosity achieved by the decomposition reaction of AB to the base of ammonia, carbon dioxide, and water vapor at 50°C enabled efficient deposition of ATH throughout the entire lung in BALB/c mice. In addition, the porous microparticles incorporating starch showed sustained ATH release characteristics (up to 5 days) and protracted antioxidant activity (up to 5 days) for 2,2-diphenyl-1-pikryl-hydrazyl (DPPH) radicals, which was comparable to that of the porous microparticles without starch which completely released ATH in 2h. Furthermore, these porous microparticles incorporating starch led to longer ATH residence (up to 20 days) in in vivo lung epithelium. We believe that this system has great pharmaceutical potential as a long-acting antioxidant for continuously relieving oxidative stress in pulmonary diseases like chronic obstructive pulmonary disease (COPD).
Assuntos
Administração por Inalação , Antioxidantes/química , Portadores de Fármacos/química , Ácido Láctico/química , Pulmão/metabolismo , Ácido Poliglicólico/química , Animais , Antocianinas/química , Antocianinas/uso terapêutico , Antioxidantes/uso terapêutico , Linhagem Celular , Portadores de Fármacos/administração & dosagem , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológicoRESUMO
Herein, we describe magnetic cell levitation models using conventional polymeric microparticles or nanoparticles as a substrate for the three-dimensional tumor cell culture. When the magnetic force originating from the ring-shaped magnets overcame the gravitational force, the magnetic field-levitated KB tumor cells adhered to the surface area of magnetic iron oxide (Fe(3)O(4))-encapsulated nano/microparticles and concentrated clusters of levitated cells, ultimately developing tumor cells to tumor spheroids. These simple cell culture models may prove useful for the screening of anticancer drugs and their formulations.
Assuntos
Técnicas de Cultura de Células/métodos , Compostos Férricos/química , Magnetismo , Nanopartículas/química , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Humanos , Ácido Láctico/química , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/químicaRESUMO
Polysaccharidic nanogels were fabricated with bovine serum albumin (BSA) and a glycol chitosan (GCS) grafted with functional 3-diethylaminopropyl (DEAP) groups. These nanogels were investigated to evaluate their cellular uptake in HeLa cells and in vivo fate in nude mice tumor model. Unlike free BSA, GCS-g-DEAP/BSA nanogels improved cellular uptake of BSA. Furthermore, this system led to an enhanced blood circulation and a high accumulation of BSA in the tumor site. Our collective results strongly support that GCS-g-DEAP/BSA nanogel is a potential carrier system for high molecular weight proteins.