کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4154932 | 1273730 | 2016 | 5 صفحه PDF | دانلود رایگان |
BackgroundGrowing evidence suggests that omega 3 fatty acid containing lipid emulsions have a beneficial effect on parenteral nutrition associated liver disease (PNALD). However, the cellular and molecular mechanisms responsible for this effect are unclear. In this study, we investigated whether Omegaven™ fish oil emulsion could inhibit lipopolysaccharidase (LPS) mediated liver damage.MethodsWe examined the effects of Omegaven™ and LPS alone and synergistically on hepatic paraoxonase 1 (PON1), a potent antioxidant protein, ERK1/2 activity, and TLR4 regulation.ResultsLPS did not alter PON1 release from HepG2 cells but did significantly decrease PON1 protein synthesis (44%, P < 0.05). Omegaven™ alone had no direct effect on PON1 release. However, it did significantly reverse LPS-mediated decrease in PON1 protein levels (control: 100%; LPS alone: 56 +/4%; LPS + Omegaven™: 87 +/6%, P < 0.05). Furthermore, molecular analysis indicated that Omegaven™ blocked LPS-mediated increase in ERK1/2 activity (35% increase), an important LPS signal transduction pathway. TLR4, the receptor for LPS, was down-regulated in the presence of Omegaven™.ConclusionOmegaven™ may be beneficial in patients with PNAC because of its ability to reverse LPS-mediated inhibition of antioxidant promoting PON1 expression, and this activity may be in part mediated by the ERK1/2 pathway.
Journal: Journal of Pediatric Surgery - Volume 51, Issue 6, June 2016, Pages 1039–1043