RESUMEN
BACKGROUND: Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon, has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice. MATERIALS AND METHODS: Sixty male BALB/C mice were randomly allocated into six groups (n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. RESULTS: Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1ß and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues. CONCLUSIONS: This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Naftoquinonas/uso terapéutico , Lesión Pulmonar Aguda/inducido químicamente , Animales , Líquido del Lavado Bronquioalveolar/química , Ciclooxigenasa 2/metabolismo , ADN/metabolismo , Lipopolisacáridos/toxicidad , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Óxido Nítrico/análisis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Peroxidasa/metabolismo , Edema Pulmonar/tratamiento farmacológicoRESUMEN
BACKGROUND: Olive oil-based lipid emulsion (LE) and medium chain triglyceride/long chain triglyceride (MCT/LCT) emulsion are both LEs with low ω-6 polyunsaturated fat acids (PUFAs) content. However, which one of these LEs is associated with a lower infection risk in patients receiving parenteral nutrition (PN) remains unclear. The aim of the study was to compare the effects of the two LEs in PN in esophageal cancer patients undergoing surgery. METHODS: Patients with resectable esophageal carcinoma were recruited and allocated randomly to two groups. The test group was given enteral nutrition (EN) with PN containing olive oil-based LE after tumor resection for ≥7 days, and the patients in the control group were supported by EN with MCT/LCT emulsion-based PN after surgery for the same time period. Immunological markers and inflammatory indicators were tested and perioperative clinical outcomes were determined. The trial was registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-13003562. 94 Patients were recruited, and grouped (olive oil-based LE, n=46 and MCT/LCT, n=48), matched for sex, age, body mass index, histological type, TNM stage, and nutrition risk screening (NRS) 2002 score. RESULTS: There were no differences in perioperative fever (>38 °C), infectious complications, length of hospital stay (>14 days), length of critical care stay (>2 days), time for oral food intake, and in-hospital mortality between the two groups. The test group showed a higher increase in IgG level compared with the MCT/LCT group (p=0.028). There was no difference in other immunological markers and inflammatory indicators between the two groups. CONCLUSION: PN containing olive oil-based or MCT/LCT LEs had similar effects on perioperative outcome, cell-mediated immune function and inflammatory response in esophageal cancer patients who had undergone surgery and were receiving EN.
Asunto(s)
Nutrición Enteral , Neoplasias Esofágicas/terapia , Emulsiones Grasas Intravenosas/administración & dosificación , Emulsiones Grasas Intravenosas/química , Nutrición Parenteral , Adulto , Anciano , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos , Método Doble Ciego , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Aceite de Oliva , Aceites de Plantas/administración & dosificación , Estudios Prospectivos , Medición de Riesgo , Aceite de Soja/administración & dosificación , Triglicéridos/administración & dosificación , Triglicéridos/química , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Magnolol, a tradition Chinese herb, displays an array of activities including antifungal, antibacterial, and antioxidant effects. To investigate the protective effect of magnolol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg). The mice received intratracheal instillation of magnolol (5 µg/kg) 30 min before LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, and myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. Expression of cyclooxygenase (COX)-2 in lung tissues was determined by Western blot analysis. Magnolol pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-α and IL-1ß in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by magnolol pretreatment. The expression of COX-2 was significantly suppressed by magnolol pretreatment. Magnolol potently protected against LPS-induced ALI and the protective effects of magnolol may attribute partly to the suppression of COX-2 expression.