Exogenous surfactant prevents hyperoxia-induced lung injury in adult mice

Abstract

Background 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. Methods Male 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. Results Compared 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. Conclusion Our 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.

The Inhibitory Effect of Curosurf® and Alveofact® on the Formation of Neutrophil Extracellular Traps

“…It is well known that surfactant proteins are also present in extrapulmonary sites such as the skin and mucosal surfaces, which has already been substantiated in previous studies ( 48 , 40 ). The accelerated skin wound healing by Alveofact ® was attributed to downregulated gene expression of TNF-α and IL-1β as well as decreased levels of macrophages ( 50 ).…”

“…Similar experiments by the same research group have revealed that the minor surfactant phospholipid palmitoyl-oleoyl-phosphatidyl-glycerol suppressed viral-elicited secretion of IL-6 and IL-8 by bronchial epithelial cells (28). Animal models and in vivo studies by van Rensburg et al and Bezerra et al have shown that exogenous surfactant administration leads to lower levels of proinflammatory biomarkers such as TNF-a, interferon (IFN)-g, and IL-2 in the bronchoalveolar lavage fluid of mice and children (40,41). Concomitantly there was increased expression of the anti-inflammatory cytokines IL-10 and IL-12 (41).…”

“…and Bezerra et al. have shown that exogenous surfactant administration leads to lower levels of proinflammatory biomarkers such as TNF-α, interferon (IFN)-γ, and IL-2 in the bronchoalveolar lavage fluid of mice and children ( 40 , 41 ). Concomitantly there was increased expression of the anti-inflammatory cytokines IL-10 and IL-12 ( 41 ).…”

Impact of synthetic surfactant CHF5633 with SP‐B and SP‐C analogues on lung function and inflammation in rabbit model of acute respiratory distress syndrome

“…Several randomized clinical trials of ARDS treatment with systemic glucocorticoids and exogenous surfactant have been conducted; however, conclusive support for efficacy has not been obtained (Dushianthan et al, 2012; Marik et al, 2008; Meng et al, 2012; Ruan et al, 2014). Using both natural and synthetic surfactant preparations, randomized clinical trials generally have shown improvements in oxygenation indices but have failed to produce any demonstrable survival benefits (Meng et al, 2012), even though the response to exogenous surfactant in direct lung injury preclinical studies has been promising (Bezerra et al, 2019; Kopincova et al, 2018; Mikolka et al, 2016; Zebialowicz Ahlstrom et al, 2019). Possible reasons for this failure of a potentially successful treatment include differences in surfactant composition, drug delivery methods, and variability in surfactant biology among the target population (Dushianthan et al, 2012).…”

A metabolic handbook for the COVID-19 pandemic

“…Levels of palmitate, the most abundant fatty acid in surfactant, are also diminished in people with ARDS 86 . Work in animal models of acute lung injury suggests that changes in surfactant metabolism may be responsible for these alterations during ARDS 87 . These findings suggest that manipulating surfactant metabolism in pulmonary epithelial cells to maintain proper composition and secretion may be beneficial for promoting disease tolerance in COVID-19 by maintaining alveolar integrity and structure ( Fig.…”