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1.
J Pineal Res ; 56(2): 196-203, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24330221

RESUMEN

Melatonin is a free radical scavenger and broad-spectrum antioxidant with immunomodulatory effects. We studied the effects of melatonin on changes in lung function, oxidative/nitrosative stress, and inflammatory cell sequestration in an acute pancreatitis (AP)-associated lung inflammation model. Acute pancreatitis was induced by injection of 5% sodium taurocholate into the pancreatic duct of rats. Animals were randomized into control, AP, and a melatonin pretreatment (10 mg/kg)/AP group. Functional residual capacity (FRC), lung compliance (Cchord), expiratory flow rate at 50% (FEF50), airway resistance index (RI), and peak expiratory flow rate (PEF) were evaluated. White blood cell count (WBC) and hydrogen peroxide, lung lavage fluid WBC, methylguanidine, protein, lactic dehydrogenase (LDH), nitric oxide (NO), and leukotriene B4 (LTB4) levels were determined. Lung wet-to-dry weight ratio, peroxynitrite, and inducible nitric oxide synthase (NOS) mRNA and protein were measured. AP induction resulted in reductions in FRC, Cchord, FEF50, and PEF, and increase in RI and lung wet-to-dry weight ratio. Blood and lung lavage fluid WBC, lavage fluid LDH, protein, and blood hydrogen peroxide also increased. Levels of hydroxyl radicals, nitric oxide, and LTB4 in lung lavage fluid, inducible NOS mRNA, protein expression, and peroxynitrite in lung tissue also were significantly elevated. Pretreatment with melatonin attenuated obstructive and restrictive ventilatory insufficiency induced by AP. Blood and lavage WBC, lavage LDH and protein, lung edema, oxidative/nitrosative stress, and lipoxygenase pathway derivatives were also significantly attenuated by melatonin. We conclude that melatonin decreases AP-induced obstructive and restrictive lung function changes via its antioxidant and anti-inflammatory properties.


Asunto(s)
Antioxidantes/uso terapéutico , Pulmón/efectos de los fármacos , Melatonina/uso terapéutico , Pancreatitis , Fenómenos Fisiológicos Respiratorios/efectos de los fármacos , Ácido Taurocólico/efectos adversos , Animales , Antioxidantes/farmacología , Peróxido de Hidrógeno , Leucocitos , Melatonina/farmacología , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Pancreatitis/fisiopatología , Ratas
2.
J Pineal Res ; 50(1): 46-53, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20964706

RESUMEN

Melatonin is a free radical scavenger with potent antioxidant properties and immunomodulatory effects. The purpose of this study was to determine the effects of orally administered melatonin in a pancreatic fluid (PF)-induced lung inflammation and airway hyperreactivity model. Aerosolized PF was introduced into airways to induce inflammation in rats. Animals were randomized into three experimental groups: sham treated; PF treated (200 µL/kg); and PF with melatonin (10 mg/kg) pretreatment. Airway reactivity to methacholine, airflow and airway resistance, bronchoalveolar lavage (BAL) cellular differential, the tumor necrosis factor α (TNFα) level, lavage nitric oxide, hydroxyl radical, and lactic dehydrogenase (LDH) were compared among groups. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFα in lung tissues were determined by real-time polymerase chain reaction. Protein expressions of iNOS and nitrotyrosine and lung tissue myeloperoxidase (MPO) activity were determined using an ELISA assay. Oral melatonin treatment indicated anti-inflammatory efficacy as evidenced by decreased methacholine sensitivity by 24% and airway obstruction by 28%, reduction in BAL eosinophil (P < 0.01) and neutrophil counts (P < 0.05), LDH (P < 0.05), and TNFα concentrations (P < 0.05) when compared to levels in sham-treated rats. Melatonin-treated animals also had reduced nitric oxide and hydroxyl radical concentrations (P < 0.05) in lavage fluid. Oral melatonin significantly reduced mRNA and protein expression of iNOS (P < 0.05 and P < 0.01, respectively), TNFα (P < 0.05), nitrotyrosine (P < 0.05), and MPO activity (P < 0.05) in lung tissues when compared with the sham-treated animals. These results suggest that oral treatment with melatonin had a beneficial effect on PF-induced obstructive ventilatory insufficiency by attenuating nitrosative and oxidative stress.


Asunto(s)
Administración Oral , Melatonina/uso terapéutico , Jugo Pancreático/inmunología , Neumonía/tratamiento farmacológico , Administración por Inhalación , Animales , Lavado Broncoalveolar , Cromatografía Líquida de Alta Presión , Ensayo de Inmunoadsorción Enzimática , Masculino , Melatonina/administración & dosificación , Nitratos/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nitritos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Neumonía/inducido químicamente , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
3.
Crit Care Med ; 34(3): 758-64, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16505662

RESUMEN

OBJECTIVES: To investigate the effects of insulin on the acute lung injury induced by lipopolysaccharide using a conscious rat model. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: A total of 190 adult male Sprague-Dawley rats weighing 250-300 g. INTERVENTIONS: Endotoxemia was induced by intravenous infusion of lipopolysaccharide. Lipopolysaccharide at various doses (0, 1, 5, 10, 20, and 30 mg/kg, n=10 for each dose) was administered intravenously in 20 mins. Insulin infusion at doses of 0.5, 1, and 5 microU/kg/min was given 5 mins before lipopolysaccharide administration. Plasma glucose was clamped at 90-110 mg/dL by infusion of 10-80% glucose solution. Insulin and glucose infusion (0.01 mL/min) was started 5 mins before lipopolysaccharide and continued for 120 mins. The rats received a total of 60, 120, and 600 microU/kg insulin as well as 0.12, 0.36, and 0.96 g of glucose in respective groups. The animals were then observed for 4 hrs. MEASUREMENTS AND MAIN RESULTS: The extent of acute lung injury was evaluated by lung weight/body weight ratio, lung weight gain, protein concentration in bronchoalveolar lavage, and exhaled nitric oxide. We also measured plasma nitrate/nitrite and methyl guanidine. In addition, histopathologic changes of the lung were examined. Lipopolysaccharide caused systemic hypotension and severe acute lung injury with increases in plasma nitrate/nitrite and methyl guanidine. Pretreatment with insulin infusion at doses of 0.5, 1, and 5 microU/kg/min mitigated or prevented systemic hypotension and the development of acute lung injury, depending on the dose. Insulin also attenuated the lipopolysaccharide-induced increases in nitrate/nitrite and methyl guanidine. CONCLUSIONS: Insulin is effective in reducing or preventing the lipopolysaccharide-induced increases in plasma nitrate/nitrite and methyl guanidine and the occurrence of acute lung injury.


Asunto(s)
Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Hiperglucemia/prevención & control , Hipoglucemiantes/farmacología , Hipotensión/prevención & control , Infusiones Intravenosas , Insulina/farmacología , Lipopolisacáridos , Pulmón/metabolismo , Pulmón/patología , Masculino , Óxido Nítrico/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
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