Abstract

BackgroundIn addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia.MethodsMale BALB/c mice (8–10 weeks), a strain highly sensitive to hyperoxia, received the exogenous surfactant-containing protein SP-B and SP-C by intranasal instillation 12 h before starting 24 h of exposure to hyperoxia in an inhalation chamber and were compared to mice receiving hyperoxia alone and to controls subjected to normoxia.ResultsCompared to the hyperoxia group, the administration of exogenous surfactant was able to reduce lung inflammation through a reduction in the influx of neutrophils and inflammatory biomarkers such as TNF, IL-17, and HMGB1 expression. The antioxidant activity prevented oxidative damage by reducing lipid peroxidation and protein carbonylation and increasing superoxide dismutase activity when compared to the hyperoxia group.ConclusionOur results offer new perspectives on the effects and the mechanism of exogenous surfactant in protecting the airway and lungs, in oxygen-rich lung microenvironment, against oxidative damage and aggravation of acute inflammation induced by hyperoxia.

Highlights

  • In addition to the risk of developing ventilator-induced lung injury, patients with Acute respiratory distress syndrome (ARDS) are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia

  • Total and differential leukocyte count in bronchoalveolar lavage fluid (BALF) Hyperoxia promoted a reduction of total leukocytes (ANOVA; P < 0.0001) and macrophages (ANOVA; P < 0.0001) compared to control and surfactant groups (p < 0.05), though the absolute levels of neutrophils (ANOVA; P = 0.0068) were significantly higher than in control group animals (p < 0.05)

  • Inflammatory markers in BALF The levels of Tumor necrosis factor (TNF), Chemokine ligand 5 (CCL5) and IL-17 in BALF were analyzed to assess the effects of exogeneous surfactant administration

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Summary

Introduction

In addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia. Studies have shown that alterations of the endogenous surfactant system contribute to pulmonary dysfunction and atelectasis in ARDS [1]. These alterations include decrease of pool size and functional modifications of endogenous surfactant. A meta-analysis of studies in adult patients with ARDS showed that exogenous surfactant (ES) administration may improve oxygenation in the first 24 h but does not mitigate mortality and long-term oxygenation (> 120 h) [2]. Important concerns have been raised, regarding the practical administration of surfactant and its ability to reach the alveoli [3].

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