Curcumin protects the developing lung against long-term hyperoxic injury

Sakurai, Reiko; Villarreal, Patricia; Husain, Sumair; Liu, Jie; Sakurai, Tokusho; Tou, Emiley; Torday, John S.; Rehan, Virender K.

doi:10.1152/ajplung.00082.2013

Cited by 45 publications

(38 citation statements)

References 36 publications

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“…In contrast, sustained NF-B activation in hyperoxia-exposed AKBI neonatal mice is associated with enhanced VEGFR2 expression, decreased apoptosis, and preserved pulmonary vessel density. The current study is supported by recent reports demonstrating that inhibiting apoptosis in the neonatal lung exposed to hyperoxia preserves lung development (48). We speculate that preservation of lung development after hyperoxic exposure could be achieved by sustaining NF-B-regulated gene expression, including VEGFR2 and antiapoptotic proteins.…”

Section: Discussionsupporting

confidence: 88%

Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice

McKenna

Michaelis

Agboke

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Neonatal mice exposed to hyperoxia develop a simplified lung structure that resembles BPD. Sustained activation of the transcription factor NF-κB and increased expression of protective target genes attenuate hyperoxia-induced mortality in adults. However, the effect of enhancing hyperoxia-induced NF-κB activity on lung injury and development in neonatal animals is unknown. We performed this study to determine whether sustained NF-κB activation, mediated through IκBβ overexpression, preserves lung development in neonatal animals exposed to hyperoxia. Newborn wild-type (WT) and IκBβ-overexpressing (AKBI) mice were exposed to hyperoxia (>95%) or room air from day of life (DOL) 0-14, after which all animals were kept in room air. Survival curves were generated through DOL 14. Lung development was assessed using radial alveolar count (RAC) and mean linear intercept (MLI) at DOL 3 and 28 and pulmonary vessel density at DOL 28. Lung tissue was collected, and NF-κB activity was assessed using Western blot for IκB degradation and NF-κB nuclear translocation. WT mice demonstrated 80% mortality through 14 days of exposure. In contrast, AKBI mice demonstrated 60% survival. Decreased RAC, increased MLI, and pulmonary vessel density caused by hyperoxia in WT mice were significantly attenuated in AKBI mice. These findings were associated with early and sustained NF-κB activation and expression of cytoprotective target genes, including vascular endothelial growth factor receptor 2. We conclude that sustained hyperoxia-induced NF-κB activation improves neonatal survival and preserves lung development. Potentiating early NF-κB activity after hyperoxic exposure may represent a therapeutic intervention to prevent BPD.

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Section: Discussionsupporting

confidence: 88%

Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice

McKenna

Michaelis

Agboke

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Also, PTX treatment increased both gene and protein expression of VEGF and improved pulmonary vascularization, but it did not show beneficial effects in terms of improving alveolarization or attenuating pulmonary fibrosis (3). Administration of curcumin, a potent anti-inflammatory and antioxidant agent, in the rat model of BPD has been shown to inhibit oxidative stress and also effectively blocked activation of TGF-␤ and subsequent hyperoxia-induced lung injury (47,48). More recently the effects of resveratrol, which exhibit anti-inflammatory and antioxidant activities, has been assessed in the rat BPD model (43).…”

Section: L954mentioning

confidence: 99%

Animal models of bronchopulmonary dysplasia. The term rat models

O’Reilly

Thébaud

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

180

149

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O'Reilly M, Thébaud B. Animal models of bronchopulmonary dysplasia. The term rat models. Am J Physiol Lung Cell Mol Physiol 307: L948 -L958, 2014. First published October 10, 2014; doi:10.1152/ajplung.00160.2014.-Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23-24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model. hyperoxia; lung development; premature birth BRONCHOPULMONARY DYSPLASIA (BPD) is the most common chronic lung disease of very preterm infants. BPD interrupts lung development and has serious long-term respiratory complications that reach beyond childhood and into adult life (8,25,26,41,53). The multifactorial etiology of BPD has prompted research to investigate the many factors contributing to the pathogenesis of BPD (reviewed in Ref. 38), with the ultimate aim of developing effective therapies to prevent longterm pulmonary sequelae. To investigate the effectiveness of various therapeutic strategies on the development, structure, and function of the lungs, it is important to have animal models that reliably reproduce some of the features observed in very preterm infants developing BPD. To achieve this, known contributing factors of BPD, such as perinatal inflammation, growth restriction, hyperoxia, and mechanical ventilation, have been used in both large and small animals to mimic the BPD-like lung injury. In particular, exposure of neonatal rats to hyperoxia is extensively utilized as a small animal model of experimental BPD. Characterization of the Rat Model of Experimental BPDExposing the immature rat lung to hyperoxic gas through neonatal life closely reproduces the histopathology observed in human infants with BPD. Studies have shown that exposure of the developing rat lung to hyperoxic gas can have detrimental effects, particularly on the structure of the gas-exchanging region (14,30,34,46,62,66). The main overall finding, which is common to each study, is that exposure of the immature lung to hyperoxic gas impairs alveolarization, resulting in fewer and enlarged alveolar air spaces. Pulmonary hypertension, disrupted vascular growth, vascular leakage, accumulation of plasma proteins, extravascular fibrin deposition, increased lung collagen content, increased inflammatory cell influx, and diso...

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“…The method was previously described for lung tissues [25]. For immunofluorescent analysis, anti-phospho-p38 (Santa Cruz Biotechnology, Santa Cruz, CA) was used.…”

Section: Immunofluorescent Analysismentioning

confidence: 99%

Substance P protects against hyperoxic-induced lung injury in neonatal rats

Huang

Shuhong

et al. 2014

Experimental Lung Research

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The aim of the study was to investigate the effects of substance P (SP) in hyperoxia-induced lung injury in newborn rats. Thirty-two rat pups were randomly divided into four groups: normoxia/saline, normoxia/SP, hyperoxia/saline and hyperoxia/SP. In a separate set of experiments, the neonatal rat pups were exposed to 21% or >95% O2 for 14 days with or without intraperitoneal administration of SP. On day 14, the animals were sacrificed and the lungs were processed for histology and biochemical analysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used for the detection of apoptosis. Antioxidant capacity was assessed by glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), oxidative stress was assessed by determining the extent of formation of malondialdehyde (MDA), activities of NADPH oxidase activity, and formation of reactive oxygen species (ROS). The activity of phospho-p38 (p-p38) and -ERK1/2 (p-ERK1/2) proteins and expression of NF-E2-related factor 2 (NRF2) were detected by Western blot, and the expression of p-p38 was detected by immunofluorescence analysis. Compared with the hyperoxia treatment, the lung damage was significantly ameliorated following the SP treatment. Furthermore, the lungs from the pups exposed to hyperoxia TUNEL-positive nuclei increased markedly and decreased significantly after SP treatment. The levels of MDA decreased and that of GSH-Px and SOD increased following the SP treatment. The SP treatment significantly suppressed the activity of NADPH oxidase and reduced ROS production. SP stimulation may result in blocking p38 MAPK and ERK signaling pathways, and the activities of p-p38 and p-ERK, and expression of NRF2 decreased following the SP treatment. These findings indicate that SP can ameliorate hyperoxic lung injury through decreasing cell apoptosis, elevating antioxidant activities, and attenuating oxidative stress.

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Curcumin protects the developing lung against long-term hyperoxic injury

Cited by 45 publications

References 36 publications

Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice

Sustained hyperoxia-induced NF-κB activation improves survival and preserves lung development in neonatal mice

Animal models of bronchopulmonary dysplasia. The term rat models

Substance P protects against hyperoxic-induced lung injury in neonatal rats

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