Liposome-entrapped antioxidant enzymes prevent lethal O2 toxicity in the newborn rat

Tanswell, A. Keith; Freeman, Bruce Α.

doi:10.1152/jappl.1987.63.1.347

Cited by 75 publications

(32 citation statements)

References 14 publications

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“…Our study confirmed that injection of 35 S-labelled DNA could be used effectively as a means to monitor DNA distribution after i.t. and i.v.…”

Section: Activity) Expression In All Lobes Of the Right Lung (R1-r4)supporting

confidence: 80%

“…Anti-human factor VIII antibodies were used to identify endothelial cells that line the blood vessels. Figure 6a shows that there was no 35 S-labelled DNA detectable in larger blood vessels. However, in this study, it was not possible to differentiate between epithelial and endothelial uptake of injected DNA in the alveolar region of the lung.…”

Section: Activity) Expression In All Lobes Of the Right Lung (R1-r4)mentioning

confidence: 99%

“…Alveolar type II cells are progenitors for type I alveolar epithelial cells and potential target cells for the gene therapeutic treatment of various lung pathologies such as oxygen toxicity, in which increased antioxidant enzyme activities in transgenic animals or protein therapy have been shown to be protective or ␣1-antitrypsin deficiency. [33][34][35][36] Recently it has been suggested 186 that CFTR is expressed in alveolar type II cell precursors and in differentiated alveolar type II cells. 37 CFTR activity has also been demonstrated in cultured rat distal lung epithelium cells.…”

Section: Activity) Expression In All Lobes Of the Right Lung (R1-r4)mentioning

confidence: 99%

“…For in situ detection the DNA was labelled with 35 S-dATP using the Nick Translation System (Promega). Ethanol precipitation was carried out twice to remove unincorporated nucleotides and labelled DNA was mixed 1:10 with unlabelled DNA before addition of DODAC:DOPE LUV liposomes.…”

Section: Immunohistochemical Staining and Autoradiographymentioning

confidence: 99%

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Comparison between intratracheal and intravenous administration of liposome–DNA complexes for cystic fibrosis lung gene therapy

Griesenbach

Chonn

Cassady³

et al. 1998

Gene Ther

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Intratracheal (i.t.) and intravenous (i.v.) delivery of DNA-Expression using either mode of administration was maxivector formulations are two strategies to obtain gene transmal 24 h after injection and declined to around 10% of day fer to the lung. It is still uncertain, however, which of these 1 levels 2 weeks after injection. For i.v. delivery of DODAC: two modes of delivery will be more effective in the treat-DOPE-DNA complexes multilamellar vesicles were more ment of cystic fibrosis and other lung diseases. In this effective than large unilamellar vesicles in all organs invesstudy, we attempted to optimize formulations of the cationic tigated. Recombinant DNA could be detected in the distal liposome DODAC:DOPE (dioleoyldimethylammoniumlung region following either route of administration. Howchloride:dioleoylphosphatidylethanolamine) complexed to ever, i.t. administration predominantly led to DNA depoplasmids encoding chloramphenicol acetyltransferase for sition in epithelial cells lining the bronchioles, eg in clara i.t. and i.v. injection into CD-1 mice and compared the two cells, whereas i.v. administration resulted in DNA depomethods. Our results showed that both methods conferred sition in the alveolar region of the lung including type II reporter gene expression in the lung that was significantly alveolar epithelial cells. higher relative to injection of plasmid DNA alone.

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“…Our study confirmed that injection of 35 S-labelled DNA could be used effectively as a means to monitor DNA distribution after i.t. and i.v.…”

Section: Activity) Expression In All Lobes Of the Right Lung (R1-r4)supporting

confidence: 80%

Section: Activity) Expression In All Lobes Of the Right Lung (R1-r4)mentioning

confidence: 99%

Section: Activity) Expression In All Lobes Of the Right Lung (R1-r4)mentioning

confidence: 99%

Section: Immunohistochemical Staining and Autoradiographymentioning

confidence: 99%

See 2 more Smart Citations

Comparison between intratracheal and intravenous administration of liposome–DNA complexes for cystic fibrosis lung gene therapy

Griesenbach

Chonn

Cassady³

et al. 1998

Gene Ther

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“…One litter was exclusively exposed to hyperoxia and the other exposed to normoxia. Mothers were alternated between the two rat pup treatment groups every 24 h to prevent previously documented adult rat oxygen toxicity (15) and any inconsistencies in pup nutrition.…”

Section: Methodsmentioning

confidence: 99%

Magnetic Resonance Imaging of Pulmonary Damage in the Term and Premature Rat Neonate Exposed to Hyperoxia

Appleby

Towner

2001

Pediatr Res

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Immaturity and oxygen toxicity have been implicated in the pathogenesis of the neonatal disease bronchopulmonary dysplasia. The present study aimed to investigate the use of magnetic resonance imaging (MRI) to assess hyperoxia-mediated lung injury in the term and premature neonate. Term (gestation, 22 d) and premature (21 d) rat pups were exposed to hyperoxia (Ͼ95%) or air for a 6-d period (n ϭ 7) and assessed for lung damage by MRI. Pulmonary signal intensities of T 1 -weighted images were significantly increased in both hyperoxia-exposed term and premature neonates, relative to air-breathing controls (p Ͻ 0.01). T 2 -weighted MRI signal intensities were also greater in premature and term rat pups exposed to hyperoxia, but failed to reach significance (p Ͼ 0.05). Elevated MRI pulmonary signal intensities may have represented an increase in magnetic resonance-detectable free water, possibly indicating an increase in edema. Corresponding histologic evidence of lung injury was detected in both term and premature rat pups exposed to hyperoxia. Histologic samples indicated focal regions of alveolar hemorrhage, immune cell infiltration, edema, and collapse in both term and premature rat neonates exposed to hyperoxia. Alveolar air space was assessed (n ϭ 5) by light microscopy within a 0.5 mm 2 region of the superior left and inferior right pulmonary lobes of each treatment group. Alveolar area of the superior left lung lobe of the premature hyperoxia treatment group was significantly smaller than other treatment groups (p Ͻ 0.05). Reduced area for respiratory exchange was probably a result of observed focal areas of edema and collapse. MRIdetectable increases in lung signal intensity may have represented an increase in hyperoxia-induced pulmonary edema in the 6-d-old rat neonate. Increases in signal intensity correlated with the appearance of edema in pulmonary histologic samples. Premature delivery had a less defined effect on lung injury but possibly exacerbated hyperoxia-mediated pulmonary damage. Normal pulmonary growth and development are disrupted at premature birth. In the premature human neonate, ventilation with elevated oxygen concentrations is often required to correct hypoxemia at room air. Hyperoxia has been implicated in the development of both RDS and BPD (1). Pulmonary oxygen toxicity has been studied in a number of species (2-4) and tends to develop into two well-described stages, representing a transition from acute to chronic lung injury. The initial acute phase involves the accumulation of proteinaceous edema and the development of fibrin-rich membranes, whereas chronic injury is characterized by metaplasia, immune cell infiltration, and fibrosis (5). Examples of hyperoxia-induced changes in pulmonary architecture have been documented in the adult (6), immature rat (7,8), and the neonatal rat pup (9).MRI is primarily based on the detection of a signal from the hydrogen nuclei of water owing to the magnetic properties of water molecules when exposed to a magnetic field. Therefore, an increase in ...

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Protective effect of exogenous transferrin against hyperoxia: A study on premature rabbits

1997

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We hypothesized that an increase in plasma iron binding capacity would decrease the generation of oxygen radicals and of lipid peroxides. To test this hypothesis, we studied whether supplementation of transferrin (TF) in premature rabbits would modify the degree of hyperoxic lung injury. Animals, delivered prematurely at 29 days of gestation (term 31 days), were randomized and given either 0.5 g/kg of albumin (Alb) (n = 116) or 0.5 g/kg of iron‐free TF (n = 132) intravenously within 2 hours after birth. Another group was randomized to receive saline (n = 15), or either 0.35 g/kg (n = 12) or 0.70 g/kg of iron‐free TF (n = 8). After exposure to a 100% oxygen environment for 2 or 4 days, the animals were killed, and plasma and bronchoalveolar lavage (BAL) fluid was recovered. Infusion of TF caused a dose‐dependent increase in the concentration of TF and an increase in the unsaturated iron‐binding capacity. Administration of TF at birth increased the gradient of TF between serum and alveolar epithelial lining fluid on day 4, suggesting decreased alveolar‐capillary permeability. BAL fluid and plasma from TF‐supplemented animals contained less lipid peroxidation products and more inhibitor of lipid peroxidation than BAL fluid or plasma from Alb‐treated animals. In TF‐treated animals, the recovery of protein in BAL fluid (TF group, 1.26 ± 0.07 mg; Alb group, 1.78 ± 0.10 mg; P = 0.02) and the water content of the extravascular lung tissue (TF group, 78.5 ± 1.4%; Alb group, 83.2 ± 1.3%; P = 0.05) were lower than in Alb‐treated animals. We propose that supplementation of iron‐free TF decreases iron‐catalyzed redox reactions and may decrease hyperoxic lung injury in the premature. Pediatr. Pulmonol. 1997; 24:429–437. © 1997 Wiley‐Liss, Inc.

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Liposome-entrapped antioxidant enzymes prevent lethal O2 toxicity in the newborn rat

Cited by 75 publications

References 14 publications

Comparison between intratracheal and intravenous administration of liposome–DNA complexes for cystic fibrosis lung gene therapy

Comparison between intratracheal and intravenous administration of liposome–DNA complexes for cystic fibrosis lung gene therapy

Magnetic Resonance Imaging of Pulmonary Damage in the Term and Premature Rat Neonate Exposed to Hyperoxia

Protective effect of exogenous transferrin against hyperoxia: A study on premature rabbits

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