RESUMEN
This study investigated the ability of aerosolized bovine lactoferrin (bLF) to protect the lungs from injury induced by chronic hyperoxia. Female CD-1 mice were exposed to hyperoxia (FiO2 = 80 %) for 7 days to induce lung injury and fibrosis. The therapeutic effects of bLF, administered via an aerosol delivery system, on the chronic lung injury induced by this period of hyperoxia were measured by bronchoalveolar lavage, lung histology, cell apoptosis, and inflammatory cytokines in the lung tissues. After exposure to hyperoxia for 7 days, the survival of the mice was significantly decreased to 20 %. The protective effects of bLF against hyperoxia were further confirmed by significant reductions in lung edema, total cell numbers in bronchoalveolar lavage fluid, inflammatory cytokines (IL-1ß and IL-6), pulmonary fibrosis, and apoptotic DNA fragmentation. The aerosolized bLF protected the mice from oxygen toxicity and increased the survival fraction to 66.7 % in the hyperoxic model. The results support the use of an aerosol therapy with bLF in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure or chronic obstructive pulmonary disease.
Asunto(s)
Hiperoxia/tratamiento farmacológico , Lactoferrina/administración & dosificación , Lesión Pulmonar/prevención & control , Administración por Inhalación , Animales , Apoptosis/efectos de los fármacos , Bovinos , Citocinas/biosíntesis , Citocinas/genética , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Hiperoxia/complicaciones , Hiperoxia/patología , Factores Inmunológicos/administración & dosificación , Inflamación/patología , Inflamación/prevención & control , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Ratones , Ratones Endogámicos ICR , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/prevención & controlRESUMEN
PURPOSE: Antrodia camphorata (AC), a highly valued polypore mushroom native only to Taiwan, has been traditionally used as a medicine for the treatment of food and drug intoxication, diarrhea, abdominal pain, hypertension, skin itching, and cancer. In this study, both of solid-state-cultured AC (S-AC) and wood-cultured AC (W-AC) were evaluated the anti-inflammatory effects on hyperoxia-induced lung injury in NF-κB-luciferase(+/+) transgenic mice. METHODS: The homozygous transgenic mice (NF-κB-luciferase(+/+)) were randomly assigned to four groups for treatment (n = 6) including Normoxia/DMSO group, Hyperoxia/DMSO group, Hyperoxia/S-AC group, and Hyperoxia/W-AC group. After 72 h of hyperoxia, we examined the bioluminescence images, reactive oxygen species (ROS), the mRNA and protein expression levels of inflammation factors, and histopathological analyses of the lung tissues. RESULTS: Hyperoxia-induced lung injury significantly increased the generation of ROS, the mRNA levels of IL-6, TNF-α, IL-1ß and IL-8, and the protein expression levels of IKKα/ß, iNOS and IL-6. Pulmonary edema and alveolar infiltration of neutrophils was also observed in the hyperoxia-induced lung tissue. However, treatment with either S-AC or W-AC obviously decreased hyperoxia-induced generation of ROS and the expression of IL-6, TNF-α, IL-1ß, IL-8, IKKα/ß and iNOS compared to hyperoxia treatment alone. Lung histopathology also showed that treatment with either S-AC or W-AC significantly reduced neutrophil infiltration and lung edema compared to treatment with hyperoxia treated alone. To find out their major compounds, eburicoic acid and dehydroeburicoic acid were both isolated and identified from S-AC and W-AC by using HPLC, MS, and NMR spectrometry. CONCLUSIONS: These results demonstrated that methanolic extracts both of S-AC and W-AC have excellent anti-inflammatory activities and thus have great potential as a source for natural health products.