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

Abstract

Background: Critically 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. Methods: Using 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. Results: PGE 2 production in the serum was highest in the LPS group, followed with Intralipid group, and the PGE 2 level of these two groups was significantly (P < 0.05) higher than the rest. Intralipid conditioning caused significantly less production of LTB 4 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. Conclusions: In 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 oilbased lipid emulsion decrease in PGE 2 and increase in LTB 4 was first time reported.

Antioxidant-Based Therapy Reduces Early-Stage Intestinal Ischemia-Reperfusion Injury in Rats

“…It has been proven that the solvent used in the preparation of the nitroindazole solution, ClinOleic ® modulates excessive inflammatory reactions [46]. However, in our study we did not found any significant effect in those animals that received ClinOleic ® as a transporter for nitroindazole.…”

“…Huang et al [46] have reported the protective effect of ClinOleic ® , by decreasing the intensity of the cytokine storm and apoptosis in an acute lung injury model. These results may seem opposed to those found in our work, however, we must take into account that in their study ClinOleic doses of 6 g/kg/day were administered for 7 consecutive days before the induction of lung damage (total dosage over 10 mL), while we administered a single dose of 0.43 mL of ClinOleic ® .…”

Novel Coronavirus Disease 2019 (COVID-19) and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology

“…This pathological condition is also known as macrophage activation syndrome (MAS) in the paediatric field [ 10 ]. Even in infectious diseases caused by Gram-negative bacteria, lipopolysaccharides (LPS), a component of Gram-negative bacteria’s outer membrane, induce cytokine storms during sepsis [ 11 ]. Hemophagocytic lymphohistiocytosis (HLH), which is also a pathological condition of CRS, stems from infectious diseases in primary immunodeficiency and from Epstein-Barr virus infections [ 12 ].…”

Effects of Omega-3 Fatty Acid on Endotoxin-induced Acute Lung Injury in Rabbits

“…에서 IL-1β의 감소 및 폐포 상피 세포의 세포자연사를 줄 임으로써 염증반응을 약화시킴을 보고하였다(Huang et al, 2020). 이는 본 연구에서의 Omegaven의 항염증 효과와 일치하는 측면이 있다.…”