Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene

Thakur, Vijay S.; Liang, Yanhong; Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Barrios, Roberto; Zhou, Guodong; Guntupalli, Bharath; Shivanna, Binoy; Maturu, Paramahamsa; Welty, Stephen E.; Moorthy, Bhagavatula; Couroucli, Xanthi I.

doi:10.1016/j.toxlet.2014.03.006

Cited by 21 publications

(5 citation statements)

References 52 publications

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“…Our results (Fig. 2A,B, E–G) showing increases in lung injury and alveolar simplification in WT (CD-1) mice following hyperoxia (85% O 2 ) was consistent with our previous studies in newborn C57BL/6J mice [29,37] and Fisher 344 rats [38] that showed similar lung phenotype after prolonged hyperoxia. Our observations showing decreased susceptibility of newborn transgenic mice carrying the human CYP1A1 -Luc promoter to lung injury and alveolar simplification supported the hypothesis that mice harboring the human CYP1A1 promoter display beneficial effects probably by modulating the endogenous expression of mouse CYP1A and phase II antioxidant enzymes such as NQO1.…”

Section: Discussionsupporting

confidence: 93%

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Jiang

Maturu

Liang

et al. 2018

Biochemical and Biophysical Research Communications

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Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this study, we tested the hypothesis that newborn transgenic mice carrying the human CYP1A1-Luc promoter will display transcriptional activation of the human CYP1A1 promoter in vivo upon exposure to hyperoxia, and that these mice will be less susceptible to hyperoxic lung injury and alveolar simplification than similarly exposed wild type (WT) mice. Newborn WT (CD-1) or transgenic mice carrying a 13.2 kb human CYP1A1 promoter and the luciferase (Luc) reporter gene (CYP1A1-luc) were maintained in room air or exposed to hyperoxia (85% O) for 7-14 days. Hyperoxia exposure of CYP1A1-Luc mice for 7 and 14 days resulted in 4- and 30-fold increases, respectively, in hepatic Luc (CYP1A1) expression, compared to room air controls. In lung, hyperoxia caused a 2-fold induction of reporter Luc at 7 days, but the induction declined after 14 days. The newborn CYP1A1-Luc mice were less susceptible to lung injury and alveolar simplification than similarly exposed wild type (WT) CD-1 mice. Also, the CYP1A1-Luc mice showed increased levels of hepatic and pulmonary CYP1A1 expression and hepatic CYP1A2 activity after hyperoxia exposure. Hyperoxia also increased NADP(H) quinone reductase (NQO1) pulmonary gene expression in both CD-1 and CYP1A1-Luc mice at both time points, but this was more pronounced in the latter at 14 days. Our results support the hypothesis that hyperoxia activates the human CYP1A1 promoter in newborn mice, and that increased endogenous expression of CYP1A1 and NADP(H) quinone reductase (NQO1) contributes to the decreased susceptibilities to hyperoxic lung injury in the transgenic animals. This is the first report providing evidence of hyperoxia-mediated transcriptional activation of the human CYP1A1 promoter in newborn mice, and this in conjunction with decreased lung injury, suggests that these phenomena have important implications for BPD.

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Section: Discussionsupporting

confidence: 93%

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Jiang

Maturu

Liang

et al. 2018

Biochemical and Biophysical Research Communications

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“…F 2 -isoprostane, a lipid peroxidation by-product is a biomarker for oxidative stress (24,56). More recently, another marker isofuran was identified, whose concentration increases under elevated O 2 levels, making combined detection of these molecules more efficient for evaluation of hyperoxia-induced oxidative stress (60).…”

Section: Resultsmentioning

confidence: 99%

Deletion of P2X7 attenuates hyperoxia-induced acute lung injury via inflammasome suppression

Galam

Rajan

Failla

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Increasing evidence shows that hyperoxia is a serious complication of oxygen therapy in acutely ill patients that causes excessive production of free radicals leading to hyperoxia-induced acute lung injury (HALI). Our previous studies have shown that P2X7 receptor activation is required for inflammasome activation during HALI. However, the role of P2X7 in HALI is unclear. The main aim of this study was to determine the effect of P2X7 receptor gene deletion on HALI. Wild-type (WT) and P2X7 knockout (P2X7 KO) mice were exposed to 100% O 2 for 72 h. P2X7 KO mice treated with hyperoxia had enhanced survival in 100% O 2 compared with the WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1␤, TNF-␣, monocyte chemoattractant protein-1, and IL-6 levels were attenuated in P2X7 KO mice. P2X7 deletion decreased lung edema and alveolar protein content, which are associated with enhanced alveolar fluid clearance. In addition, activation of the inflammasome was suppressed in P2X7-deficient alveolar macrophages and was associated with suppression of IL-1␤ release. Furthermore, P2X7-deficient alveolar macrophage in type II alveolar epithelial cells (AECs) coculture model abolished protein permeability across mouse type II AEC monolayers. Deletion of P2X7 does not lead to a decrease in epithelial sodium channel expression in cocultures of alveolar macrophages and type II AECs. Taken together, these findings show that deletion of P2X7 is a protective factor and therapeutic target for the amelioration of hyperoxia-induced lung injury. acute lung injury; P2X7; NLRP3; inflammasome; hyperoxia ACUTE LUNG INJURY (ALI) IS a major clinical problem in the United States, accounting for one of the primary causes of in-hospital hypoxemic respiratory failure leading to morbidity and mortality (48). Prolonged exposure to hyperoxia has been conclusively demonstrated to cause ALI (22,58,62). Furthermore, numerous cardiovascular and pulmonary diseases require oxygen therapy (22, 28 -30, 58). Therefore, it is pertinent to understand the mechanism of damage in ALI, wherein the pathology manifests as alveolar damage from immune cell infiltration and pulmonary edema (31,63).Prolonged exposure to oxygen concentrations of FI O 2 Ͼ 0.8 has previously been shown to cause mortality in small animal and higher-order primate models (26). Hyperoxia-induced lung injury contributes to increasing the production of reactive oxygen species (ROS), inflammatory cytokines, as well as exudative pulmonary edema, collagen deposition, and damage to the alveolar epithelium (26, 32). Thus, using hyperoxia as a form of oxygen toxicity is clinically relevant to study the pathophysiology of ALI. In ALI, the disruption of the fine balance between proinflammatory and anti-inflammatory agents is the basic pathology with a concomitant activation of apoptotic signals (33, 59, 62). IL-1␤ was discovered to be one of the early inflammatory cytokines to appear in ALI patients and cause the release of additional cytokines (18). The caspase-1-mediated acti...

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“…It is well-established that long-term hyperoxia causes ALI characterised by oxidative stress and enhanced cell death [ 19 ]. Scarce data, however, are only available on the interaction between CS exposure and hyperoxia: pre -natal exposure to the CS component benzo[ a ]pyrene potentiated immediate post -natal hyperoxic lung injury [ 20 ], and long-term (over five days) post -natal exposure to hyperoxia had an additive effect on the histological lung damage and organ dysfunction in CS-induced COPD during adulthood [ 21 ]. However, in various animal models resulting from haemorrhage [ 22 – 25 ], ischemia/reperfusion injury [ 26 , 27 ] and poly-microbial sepsis [ 28 – 30 ] short-term ventilation with 100% O 2 resulted in attenuated inflammation and reduced apoptosis [ 26 , 27 , 29 – 32 ], and ultimately improved organ function and survival.…”

Section: Introductionmentioning

confidence: 99%

Blunt Chest Trauma in Mice after Cigarette Smoke-Exposure: Effects of Mechanical Ventilation with 100 % O2

Wagner

Gröger²,

McCook³

et al. 2015

PLoS ONE

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Cigarette smoking (CS) aggravates post-traumatic acute lung injury and increases ventilator-induced lung injury due to more severe tissue inflammation and apoptosis. Hyper-inflammation after chest trauma is due to the physical damage, the drop in alveolar PO2, and the consecutive hypoxemia and tissue hypoxia. Therefore, we tested the hypotheses that 1) CS exposure prior to blunt chest trauma causes more severe post-traumatic inflammation and thereby aggravates lung injury, and that 2) hyperoxia may attenuate this effect. Immediately after blast wave-induced blunt chest trauma, mice (n=32) with or without 3-4 weeks of CS exposure underwent 4 hours of pressure-controlled, thoraco-pulmonary compliance-titrated, lung-protective mechanical ventilation with air or 100 % O2. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1 (HO-1), activated caspase-3, and hypoxia-inducible factor 1-α (HIF-1α) expression, nuclear factor-κB (NF-κB) activation, nitrotyrosine formation, purinergic receptor 2X4 (P2XR4) and 2X7 (P2XR7) expression, and histological scoring. CS exposure prior to chest trauma lead to higher pulmonary compliance and lower PaO2 and Horovitz-index, associated with increased tissue IL-18 and blood MCP-1 concentrations, a 2-4-fold higher inflammatory cell infiltration, and more pronounced alveolar membrane thickening. This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression. Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice. However, hyperoxia attenuated tissue HIF-1α, nitrotyrosine, P2XR7, and P2XR4 expression, while it increased HO-1 formation in CS exposed mice. Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.

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Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene

Cited by 21 publications

References 52 publications

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Deletion of P2X7 attenuates hyperoxia-induced acute lung injury via inflammasome suppression

Blunt Chest Trauma in Mice after Cigarette Smoke-Exposure: Effects of Mechanical Ventilation with 100 % O2

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