8-11-14-eicosatrienoic-acid and Acute-Lung-Injury

Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations.. Prospective, blinded, randomized, controlled, multicenter trial.. PICU.. Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome.. Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7.. At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers.. Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Topics: 8,11,14-Eicosatrienoic Acid; Acute Lung Injury; Antioxidants; Arachidonic Acid; Biomarkers; Child; Child, Preschool; Dietary Supplements; Double-Blind Method; Eicosapentaenoic Acid; Energy Intake; Enteral Nutrition; Feasibility Studies; Female; Food, Formulated; gamma-Linolenic Acid; Humans; Immunomodulation; Male; Respiration, Artificial; Respiratory Distress Syndrome

Acute lung injury (ALI) is characterized by rapid alveolar injury, vascular leakage, lung inflammation, neutrophil accumulation, and induced cytokines production leading to lung edema. The mortality rate of patients suffering from ALI remains high. Epoxyeicosatrienoic acids (EETs) are cytochrome P450-dependent derivatives of polyunsaturated fatty acid with antihypertensive, profibrinolytic, and anti-inflammatory functions. EETs are rapidly hydrated by soluble epoxide hydrolase (sEH) to their less potent diols. The aim of this study was to investigate the role of sEH inhibitor trifluoromethoxyphenyl propionylpiperidin urea (TPPU) and EETs in lipopolysaccharide (LPS)-induced ALI of mice. Our studies revealed that inhibition of sEH with TPPU attenuated the morphological changes in mice, decreased the neutrophil infiltration to the lung, pro-inflammatory cytokine levels (IL-1β and TNF-α) in serum and bronchoalveolar lavage fluid (BALF), and alveolar capillary leakage (lung wet/dry ratio and total protein concentration in BALF). TPPU improved the survival rate of LPS-induced ALI. In addition, in vitro experiments revealed that both TPPU and EETs (11,12-EET and 14,15-EET) suppressed the expression of IL-1β and TNF-α, and LDH release in RAW264.7 cells. These results indicate that EETs play a role in dampening LPS-induced acute lung inflammation, and suggest that sEH could be a valuable candidate for the treatment of ALI.

Topics: 8,11,14-Eicosatrienoic Acid; Acute Lung Injury; Animals; Anti-Inflammatory Agents; Epoxide Hydrolases; Interleukin-1beta; Lipopolysaccharides; Mice; NF-kappa B; Pneumonia; RAW 264.7 Cells; Tumor Necrosis Factor-alpha