The administration of a pre-digested fat enriched formula prevents NEC-induced lung injury in mice

2021 ◽  
pp. 1-31
Author(s):  
Chhinder P. Sodhi ◽  
Andres J. Gonzalez Salazar ◽  
Mark Kovler ◽  
William B. Fulton ◽  
Yukihiro Yamaguchi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Injury ◽  
Gastrointestinal Disease ◽  
Reactive Oxygen ◽  
Surfactant Protein ◽  
Oxygen Species ◽  
Lung Maturation ◽  
Newborn Mice ◽  
Lung Protection ◽  
Severe Lung

Abstract Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurity that typically develops after the administration of infant formula, suggesting a link between nutritional components and disease development. One of the most significant complications that develops in patients with NEC is severe lung injury. We have previously shown that the administration of a nutritional formula that is enriched in pre-digested triglycrides that do not require lipase action can significantly reduce the severity of NEC in a mouse model. We now hypothesize that this 'pre-digested fat system (PDF)' may reduce NEC-associated lung injury. In support of this hypothesis, we now show that rearing newborn mice on a nutritional formula based on the 'pre-digested fat (PDF) system’ promotes lung development, as evidenced by increased tight junctions and surfactant protein expression. Mice who were administered this 'PDF fat system’ were significantly less vulnerable to the development of NEC-induced lung inflammation, and the administration of the 'PDF fat system’ conferred lung protection. In seeking to define the mechanisms involved, the administration of the PDF system’ significantly enhanced lung maturation and reduced the production of reactive oxygen species (ROS). These findings suggest that the PDF system protects the development of NEC-induced lung injury through effects on lung maturation and reduced reactive oxygen species in the lung, and also increase lung maturation in non-NEC mice.

scholarly journals High Concentrations of Reactive Oxygen Species in the BAL Fluid Are Correlated with Lung Injury in Rabbits after Hemorrhagic Shock and Resuscitation

2009 ◽  
Vol 219 (3) ◽  
pp. 193-199 ◽  
Author(s):  
Marios-Konstantinos Tasoulis ◽  
Olga Livaditi ◽  
Michalis Stamatakos ◽  
Charikleia Stefanaki ◽  
Pantelis Paneris ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Injury ◽  
Hemorrhagic Shock ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
High Concentrations

scholarly journals Association of Toll-Like Receptor Signaling and Reactive Oxygen Species: A Potential Therapeutic Target for Posttrauma Acute Lung Injury

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Meng Xiang ◽  
Janet Fan ◽  
Jie Fan
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Therapeutic Target ◽  
Major Trauma ◽  
Pulmonary Inflammation ◽  
Reactive Oxygen ◽  
Oxygen Species

Acute lung injury (ALI) frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS). Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMϕ) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

Reactive Oxygen Species Contribute to Oxygen-Related Lung Injury After Acid Aspiration

1998 ◽  
Vol 87 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Nader Nader-Djalal ◽  
Paul R. Knight ◽  
Kuldip Thusu ◽  
Bruce A. Davidson ◽  
Bruce A. Holm ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Injury ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Acid Aspiration

scholarly journals Anti-Inflammatory and Reactive Oxygen Species Suppression through Aspirin Pretreatment to Treat Hyperoxia-Induced Acute Lung Injury in NF-κB–Luciferase Inducible Transgenic Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 429 ◽  
Author(s):  
Chuan-Mu Chen ◽  
Yu-Tang Tung ◽  
Chi-Hsuan Wei ◽  
Po-Ying Lee ◽  
Wei Chen
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
In Vivo Imaging ◽  
Reactive Oxygen ◽  
Luciferase Expression ◽  
Oxygen Species ◽  
Anti Inflammatory

Acute lung injury (ALI), a common cause of morbidity and mortality in intensive care units, results from either direct intra-alveolar injury or indirect injury following systemic inflammation and oxidative stress. Adequate tissue oxygenation often requires additional supplemental oxygen. However, hyperoxia causes lung injury and pathological changes. Notably, preclinical data suggest that aspirin modulates numerous platelet-mediated processes involved in ALI development and resolution. Our previous study suggested that prehospital aspirin use reduced the risk of ALI in critically ill patients. This research uses an in vivo imaging system (IVIS) to investigate the mechanisms of aspirin’s anti-inflammatory and antioxidant effects on hyperoxia-induced ALI in nuclear factor κB (NF-κB)–luciferase transgenic mice. To define mechanisms through which NF-κB causes disease, we developed transgenic mice that express luciferase under the control of NF-κB, enabling real-time in vivo imaging of NF-κB activity in intact animals. An NF-κB-dependent bioluminescent signal was used in transgenic mice carrying the luciferase genes to monitor the anti-inflammatory effects of aspirin. These results demonstrated that pretreatment with aspirin reduced luciferase expression, indicating that aspirin reduces NF-κB activation. In addition, aspirin reduced reactive oxygen species expression, the number of macrophages, neutrophil infiltration and lung edema compared with treatment with only hyperoxia treatment. In addition, we demonstrated that pretreatment with aspirin significantly reduced the protein levels of phosphorylated protein kinase B, NF-κB and tumor necrosis factor α in NF-κB–luciferase+/+ transgenic mice. Thus, the effects of aspirin on the anti-inflammatory response and reactive oxygen species suppressive are hypothesized to occur through the NF-κB signaling pathway. This study demonstrated that aspirin exerts a protective effect for hyperoxia-induced lung injury and thus is currently the drug conventionally used for hyperoxia-induced lung injury.

scholarly journals Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Sashko Georgiev Spassov ◽  
Rosa Donus ◽  
Paul Mikael Ihle ◽  
Helen Engelstaedter ◽  
Alexander Hoetzel ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Sulfide ◽  
Lung Injury ◽  
Inflammatory Responses ◽  
Reactive Oxygen ◽  
Akt Signaling ◽  
Lung Damage ◽  
Oxygen Species ◽  
Ventilator Induced Lung Injury ◽  
Oxidative Processes

The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S. In addition, phosphorylation of the signaling protein Akt was induced by H2S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H2S. Moreover, the ability of H2S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H2S-mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury.

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