RESUMO
BACKGROUND: Intake of polyphenols and polyphenol-rich fruit extracts has been shown to reduce markers of inflammation, diabetes, and hepatic complications that result from the consumption of a high-fat (HF) diet. OBJECTIVE: The objective of this study was to determine whether mice fed polyphenol-rich apple peel extract (AE), cherry extract (CE), and quercetin, a phytochemical abundant in fruits including apples and cherries, would modulate the harmful effects of adiposity on blood glucose regulation, endocrine concentrations, and hepatic metabolism in HF-fed C57BL/6J male mice. METHODS: Groups of 8-wk-old mice (n = 8 each) were fed 5 diets for 10 wk, including low-fat (LF; 10% of total energy) and HF (60% of total energy) control diets and 3 HF diets containing polyphenol-rich AE, CE, and quercetin (0.2% wt:wt). Also, an in vitro study used HepG2 cells exposed to quercetin (0-100 µmol/L) to determine whether intracellular lipid accumulation could be modulated by this phytochemical. RESULTS: Mice fed the HF control diet consumed 36% more energy, gained 14 g more body weight, and had â¼50% elevated blood glucose concentrations (all P < 0.05) than did LF-fed mice. Mice fed HF diets containing AE, CE, or quercetin became as obese as HF-fed mice, but had significantly lower blood glucose concentrations after food deprivation (-36%, -22%, -22%, respectively; P < 0.05). Concentrations of serum C-reactive protein were reduced 29% in quercetin-fed mice compared with HF-fed controls (P < 0.05). A qualitative evaluation of liver tissue sections suggested that fruit phytochemicals may reduce hepatic lipid accumulation. A quantitative analysis of lipid accumulation in HepG2 cells demonstrated a dose-dependent decrease in lipid content in cells treated with 0-100 µmol quercetin/L (P < 0.05). CONCLUSIONS: In mice, consumption of AE, CE, or quercetin appears to modulate some of the harmful effects associated with the consumption of an obesogenic HF diet. Furthermore, in a cell culture model, quercetin was shown to reduce intracellular lipid accumulation in a dose-dependent fashion.
Assuntos
Glicemia/metabolismo , Frutas/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Obesidade , Receptores Ativados por Proliferador de Peroxissomo/genética , Quercetina/farmacologia , Animais , Proteína C-Reativa/metabolismo , Dieta Hiperlipídica , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Fígado/metabolismo , Masculino , Malus/química , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/genética , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Prunus avium/químicaRESUMO
P-glycoprotein (P-gp) is a promiscuous small molecule transporter whose overexpression in cancer is associated with multidrug resistance (MDR). In these instances, anticancer drugs can select for P-gp-overexpressing cells, leading to cancer recurrence with an MDR phenotype. To avoid selection for MDR cancers and inform individual patient treatment plans, it is critical to noninvasively identify P-gp-overexpressing tumors prior to administration of chemotherapy. We report the facile free radical copolymerization of quinidine, a competitive inhibitor of P-gp, and acrylic acid to generate multiplexed polymeric P-gp-targeted imaging agents with tunable quinidine content. Copolymer targeting was demonstrated in a nude mouse xenograft model. In xenografts overexpressing P-gp, copolymer distribution was enhanced over two-fold compared to the negative control of poly(acrylic acid) regardless of quinidine content. In contrast, accumulation of the copolymers in xenografts lacking P-gp was equivalent to poly(acrylic acid). This work forms the foundation for a unique approach toward the phenotype-specific noninvasive imaging of MDR tumors and is the first in vivo demonstration of copolymer accumulation through the active targeting of P-gp.
Assuntos
Antineoplásicos , Neoplasias , Camundongos , Animais , Humanos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Quinidina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/farmacologia , Polímeros/farmacologiaRESUMO
Electrogenerated chemiluminescence (ECL) is the production of light via electron transfer reactions between electrochemically produced reagents. ECL-based biosensors use specific biological interactions to recognize an analyte and produce a luminescent signal. Biosensors fabricated with novel biorecognition species have increased the number of analytes detected. Some of these analytes include peptides, cells, enzymes and nucleic acids. ECL biosensors are selective, simple, sensitive and have low detection limits. Traditional methods use ruthenium complexes or luminol to generate ECL. Nanomaterials can be incorporated into ECL biosensors to improve efficiency, but also represent a new class of ECL emitters. This article reviews the application of ruthenium complex, luminol and nanomaterial-based ECL biosensors to making measurements in biological matrices over the past 4 years.
Assuntos
Técnicas Biossensoriais , Complexos de Coordenação/química , Medições Luminescentes , Aptâmeros de Nucleotídeos/química , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Imunoensaio , Luminol/química , Nanoestruturas/química , Rutênio/químicaRESUMO
Soy isoflavones exert beneficial health effects; however, their potential to ameliorate conditions associated with the metabolic syndrome (MetS) has not been studied in detail. In vitro and in vivo models were used to determine the effect of isoflavones on lipid metabolism, inflammation, and oxidative stress. In nude mice, consumption of Novasoy (NS) increased cholesterol and lipid metabolism gene expression, including Scd-1 (27.7-fold), Cyp4a14 (35.2-fold), and Cyp4a10 (9.5-fold), and reduced anti-inflammatory genes, including Cebpd (16.4-fold). A high-fat (HF) diet containing 0.4% (w/w) NS for 10 weeks significantly reduced percent weight gain (74.6 ± 2.5 vs 68.6 ± 3.5%) and hepatic lipid accumulation (20 ± 1.2 vs 27 ± 1.5%), compared to HF alone (p < 0.05) in C57BL/6J mice. NS also increased lipid oxidation and antioxidant gene expression while decreasing inflammatory cytokines. In vitro analysis in HepG2 cells revealed that genistein dose-dependently decreases oleic acid-induced lipid accumulation. Soy isoflavones may ameliorate symptoms associated with MetS via anti-inflammatory, antioxidant, and hypolipidemic modulation.