Molecular mechanisms underlying hyperoxia acute lung injury

Abstract

The management of acute hypoxemic respiratory failure frequently includes the use of supraphysiological fractions of inspired oxygen (FiO), which can be beneficial in the short-term but not without risks in the long-term, causing acute lung injury (ALI). Over the last few years, much attention has been devoted to the intracellular signaling transduction pathways that lead to hyperoxia-induced cell damage, particularly MAP kinase cascades. Identification of involved signaling molecules and understanding of the regulation of the main signal transduction pathways might provide the basis for improving the outcome of patients under high FiO exposure through more effective therapeutic interventions. This review, which includes studies published from 1987 to 2015, presents an overview on recent progresses in the hyperoxia ALI field with special emphasis on potential therapeutic targets and clinical approaches based on the molecular mechanisms underlying hyperoxia-induced inflammation. Further studies are needed to gain deeper insight into controversial molecular mechanisms underlying hyperoxia-induced cell death, which may play a critical role in future pharmacological interventions, as well as into hyperoxia-induced cell damage, that could monitor and therefore prevent hyperoxia ALI.

Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1

“…Damaged epithelial-endothelial barriers can increase the flux of cells and their debris from the vasculature into the airspaces, thereby increasing the total protein content in the airways [2,9,12]. Consequently, assessing the total protein content in BALF has been postulated to be a marker of lung injury [33].…”

“…The clinical management of ARDS primarily involves the use of mechanical ventilation with supraphysiological concentrations of oxygen (i.e., hyperoxia) [1]. Although mechanical ventilation is a life-saving intervention for patients with respiratory distress or failure, it can exacerbate injury in previously damaged lungs [2,3], resulting in significantly high morbidity and mortality rates in patients on ventilation [4,5]. Prolonged exposure to hyperoxia can cause hyperoxia-induced acute lung injury (HALI).…”

“…The prolonged exposure to hyperoxia can induce excessive generation of reactive oxygen species (ROS), particularly superoxide, by both the mitochondrial electron transport chain and NADPH oxidases [2,9,11]. The excessive production of ROS can damage lung cells and produce pulmonary dysfunction [2,9,12].…”

“…The prolonged exposure to hyperoxia can induce excessive generation of reactive oxygen species (ROS), particularly superoxide, by both the mitochondrial electron transport chain and NADPH oxidases [2,9,11]. The excessive production of ROS can damage lung cells and produce pulmonary dysfunction [2,9,12]. For example, hyperoxia-induced oxidative stress adversely affects alveolar macrophage function in phagocytosis, leading to decreased clearance of invading pathogens including bacteria [13][14][15][16].…”

Reactive oxygen and nitrogen species induce cell apoptosis via a mitochondria‐dependent pathway in hyperoxia lung injury

“…1 Recently, the recognition of the hyperoxiainduced lung injury mechanism has been deepened constantly with the rapid development of medical science. Hyperoxia prevented the production of alveolar cells and blood vessels and caused inflammation and abnormal inflammatory cells accumulation and fibrosis, resulting in alveolar fiber deposition and oxidation.…”