RESUMEN
Neutrophil extracellular traps (NETs) represent an innate organism defense mechanism characterized by neutrophil release of intracellular material to capture any aggressor agent. Elevated NETs release is associated with increased inflammatory response and related diseases, such as obesity. Chronic physical training is one of the main strategies to treat and prevent obesity. The relationship between physical training and NETs is still under study. The present review, followed by a bioinformatics analysis, demonstrates the meaningful connection between physical exercise, obesity, and NETs. The bioinformatics indicated TNF-α as a leading gene after the ontological analysis followed by positive-interleukin-6 regulation, chemokines, and inflammatory response regulation. The main results pointed to a relevant regulatory effect of physical training on NETs release, indicating physical exercise as a possible therapeutic target on modulating NETs and inflammation.
Asunto(s)
Ejercicio Físico/genética , Inflamación/genética , Obesidad/genética , Factor de Necrosis Tumoral alfa/genética , Biología Computacional , Trampas Extracelulares/genética , Humanos , Inflamación/fisiopatología , Inflamación/terapia , Neutrófilos/metabolismo , Obesidad/fisiopatología , Obesidad/terapiaRESUMEN
The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Lactococcus lactis/metabolismo , Hígado/efectos de los fármacos , Probióticos/farmacología , Resveratrol/farmacología , Administración Oral , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Colesterol/sangre , Biología Computacional , Femenino , Regulación de la Expresión Génica/genética , Ontología de Genes , Inmunohistoquímica , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/microbiología , Interleucina-6/genética , Interleucina-6/metabolismo , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Resveratrol/administración & dosificación , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Solanum lycocarpum is a medicinal plant used in Brazil with hypoglycemic activity by its fruits use. However, the fruits production is restricted in some periods of the year, differently of leaves. OBJECTIVE: To evaluate the effects of hydroalcoholic extracts of S. lycocarpum leaves in alloxan-induced diabetic mice. METHODS: Hydroalcoholic extract of S. lycocarpum was characterized by phytochemical and GCMS analysis. The Antidiabetic activity was assessed following treatment for 22 days with S. lycocarpum extract at 125, 250, and 500 mg/kg. Bodyweight, water, and food intake, glycemia, biochemical parameters, anatomy-histopathology of the pancreas, liver and kidney, and expression of target genes were analyzed. In addition, oral acute toxicity was evaluated. RESULTS: Animals treated showed a significant reduction (p < 0.05) in glycemia following a dose of 125 mg/kg. Food intake remained similar for all groups. Decreased polydipsia symptoms were observed after treatment with 250 (p < 0.001) and 500 mg/kg (p < 0.01) compared with diabetic control, although normal rates were observed when 125 mg/kg was administered. A protective effect was also observed in the pancreas, liver, and kidneys, through the regeneration of the islets. Hypoglycemic activity can be attributed to myo-inositol, which stimulates insulin secretion, associated with α-tocopherol, which prevents damage from oxidative stress and apoptosis of ß-pancreatic cells by an increased Catalase (CAT) and Glutathione peroxidase 4 (GPX4) mRNA expression. The toxicological test demonstrated safe oral use of the extract under the present conditions. CONCLUSION: Hydroalcoholic extract of S. lycocarpum promotes the regulation of diabetes in the case of moderate glycemic levels, by decreasing glycemia and exerting protective effects on the islets.
Asunto(s)
Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Solanum/química , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Aloxano/administración & dosificación , Animales , Aspartato Aminotransferasas/metabolismo , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Hipoglucemiantes/química , Inositol/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Extractos Vegetales/química , Hojas de la Planta/química , alfa-Tocoferol/farmacologíaRESUMEN
A three-phase, liquid-phase microextraction using a hollow fibre (HF-LPME) combined with high performance liquid chromatography-fluorescence detection (HPLC-FL) was developed for the analysis of fluoxetine (FLX) and its active metabolite, norfluoxetine (NFLX), in human plasma. An HF-LPME system using a disposable 7-cm polypropylene porous hollow fibre, 5 mL of alkaline plasma solution (donor phase), n-hexyl ether (extraction solvent) and 20 mM hydrochloric acid (acceptor phase) was used in the extraction. The method was validated after optimisation of several parameters that influence LPME efficiency. A reverse-phase LiChrospher 60 RP-Select B column (125 mm x 4 mm, 5 microm particle size) was used with 0.005 M sodium acetate buffer (pH 4.5) and acetonitrile at a 50:50 (v/v) as the mobile phase at a flow rate of 0.6 mL min(-1). In these conditions satisfactory chromatographic resolution and efficiency for the analytes were obtained. Fluorescence detection at 230 nm excitation wavelength and 290 nm emission wavelength was performed. Linearity over a range of 5-500 ng mL(-1), with determination coefficients (R(2)) of 0.9999 and 0.9962 for FLX and NFLX, respectively, was established. Venlafaxine was used as the internal standard for both analytes. Extraction recoveries from plasma samples were 70.9% for FLX and 59.7% for NFLX. The intra-day coefficients of variation (CVs) were below 5.4%, and inter-day CVs were below 13.0%, for both analytes at concentrations of 20, 80 and 160 ng mL(-1). HF-LPME extraction followed by HPLC-FL detection for FLX and NFLX analyses demonstrated excellent sample clean-up and selectivity. This method was simple, cheap, and easy to perform, yielding substantial analytes enrichment. The method was applied to the analysis of samples from 12 patients under fluoxetine treatment and proved suitable for routine therapeutic drug monitoring for this antidepressant.