Abstract
The study aimed to prove the hypothesis that exogenous surfactant and an antibiotic polymyxin B (PxB) can more effectively reduce lipopolysaccharide (LPS)-induced acute lung injury (ALI) than surfactant treatment alone, and to evaluate the effect of this treatment on the gene expression of surfactant proteins (SPs). Anesthetized rats were intratracheally instilled with different doses of LPS to induce ALI. Animals with LPS 500 μg/kg have been treated with exogenous surfactant (poractant alfa, Curosurf®, 50 mg PL/kg b.w.) or surfactant with PxB 1% w.w. (PSUR + PxB) and mechanically ventilated for 5 hrs. LPS at 500 μg/kg increased lung edema, oxidative stress, and the levels of proinflammatory mediators in lung tissue and bronchoalveolar lavage fluid (BALF). PSUR reduced lung edema and oxidative stress in the lungs and IL-6 in BALF. This effect was further potentiated by PxB added to PSUR. Exogenous surfactant enhanced the gene expression of SP-A, SP-B, and SP-C, however, gene expression for all SPs was reduced after treatment with PSUR + PxB. In mechanically ventilated rats with LPS-induced ALI, the positive effect of exogenous surfactant on inflammation and oxidative stress was potentiated with PxB. Due to the tendency for reduced SPs gene expression after surfactant/PxB treatment topical use of PxB should be considered with caution.
Highlights
Bacterial endotoxin is the major component of the outer membrane of Gram-negative bacteria [1]
Administration of LPS 100 μg/kg evoked an increase in Interleukin 1β (IL-1β) and monocyte chemotactic protein 1 (MCP1)
It was stated that the complexing of endotoxin with a pulmonary surfactant contribute to pathological changes observed in pneumonia and these changes have been may contribute to pathological changes observed in pneumonia and these changes haveattributed been to surfactant alterations
Summary
Bacterial endotoxin (lipopolysaccharide, LPS) is the major component of the outer membrane of Gram-negative bacteria [1]. It binds to the toll-like receptor (TLR). Complex CD14/TLR4/MD-2 on cellular membranes [2]. It interacts with the pulmonary surfactant, a lipoprotein material lining the inner surface of the lung, which is an important component of the innate host defense against invading pathogens [3]. Activation of TLRs leads to an increase in transcription factor NF-κB, activator protein 1, and interferons, and induces both pro-inflammatory and pro-oxidative pathways [4] which may result in acute respiratory distress syndrome (ARDS). Due to the high morbidity and mortality of ARDS, new possibilities in the treatment are being intensively sought [5]. While in neonatal RDS of prematurity exogenous surfactant replacement is routinely used, Molecules 2020, 25, 4356; doi:10.3390/molecules25194356 www.mdpi.com/journal/molecules
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