Preconditioning rats with three lipid emulsions prior to acute lung injury affects cytokine production and cell apoptosis in the lung and liver

Li-Mi Huang,Qingqing Hu,Xin-He Lai,Yan Qian,Xiaoxia Huang

doi:10.1186/s12944-019-1137-x

Abstract

BackgroundCritically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. We sought to study whether preconditioning with representative of lipid emulsions for one week could benefit rats from ALI.MethodsUsing a lipopolysaccharide (LPS)-induced ALI rat model and techniques such as polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.ResultsPGE2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB4 than the LPS, Clinoleic, or Omegaven group. In contrast to Intralipid, rats pretreated with Clinoleic or Omegaven significantly decreased their production of inflammatory mediators (IL-1 β, IL-6 and TNF-α), had less apoptosis in the lung tissues, and Omegaven greatly improved liver function upon lipopolysaccharide (LPS) challenge.ConclusionsIn an ALI setting, preconditioning with Omegaven or Clinoleic was better than Intralipid in decreasing the intensity of the cytokine storm and apoptosis caused by LPS challenge, and Omegaven in addition had the potential to improve liver function. The results from the present study set a basis for further investigation of the molecular mechanisms of ALI, including the up- and downstream pathways of proinflammatory factor production, in search of (small) molecules intervening with the pathogenesis of ALI in order to translate relevant research findings into clinical benefit for patients with ALI. The use of Omegaven or Clinoleic, particularly in patients with ALI, is still characterized by uncertainty due to a lack of relevant studies. Future investigations must specifically focus on the route of administration and mode of application (enteral vs. parenteral/bolus vs. continuous), determining an optimal dose of Omegaven or Clinoleic, and the defining the best timepoint(s) for administration. Critically ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. The effect of lipid emulsion via parenteral nutrition on liver function was first time evaluated in rats in an ALI setting. The comparison of three forms of lipid emulsion in a rat model of acute lung injury was first time studied. The fish oil-based lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

Highlights

Ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition
Histopathology of lung injury of the ALI rats preconditioned with different lipid emulsions Compared to the almost normal histology of the saline group at 8 h post-challenge with saline, all the rats challenged with LPS exhibited intra-alveolar/interstitial patchy hemorrhages, interstitial edema and peribronchial infiltration of inflammatory cells, without any significant difference among the groups (Fig. 1)
Apoptosis of epithelial lung cells of the ALI rats preconditioned with different lipid emulsions upon LPS challenge The apoptosis was measured by transferase dUTP nick end labeling (TUNEL) assay and the results demonstrated that lung tissue sections of rats from the saline + LPS treatment group included significantly more apoptotic cells compared with the Clinoleic or Omegaven groups (Fig. 3)

Summary

Introduction

Ill patients are at higher risk having acute lung injury (ALI) and more often in need of parenteral nutrition. Due to its importance in ALI pathogenesis, administration of LPS intratracheally in vivo is widely accepted as one of the most common models of ALI with a clinical relevance [5, 6]. Ill patients, such as those with acute respiratory distress syndrome (the more severe form of ALI) often require parenteral nutrition, and lipid emulsions are crucial for providing essential fatty acids [7,8,9,10], but with the associated risk of causing parenteral nutritionassociated liver disease [11,12,13]. Among the lipid emulsion brands approved for parenteral nutrition, Intralipid and Omegaven are almost pure soybean or fish oil (FO) products, whereas Clinoleic contains 80% olive oil and 20% soybean oil [14]

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Discussion

Conclusion