کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5718512 | 1411252 | 2017 | 6 صفحه PDF | دانلود رایگان |
PurposeParenteral nutrition associated liver disease (PNALD) develops in a subset of children receiving parenteral nutrition for intestinal failure. Omegaven⢠is an omega-3 fatty acid (Ω3FA) lipid emulsion high in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) that can lessen PNALD. Inflammatory cytokines (IL-1, TNF-α, TGF-β) are elevated in PNALD and can decrease paraoxonase 1 protein expression (PON1). We sought to determine the effect of Omegavenâ¢, EPA, and DHA on inflammatory cytokines TNF-α, IL-1, and TGF-β via ERK1/2 and p-Smad2/3 signaling pathways as well as the changes in intracellular PON1 protein expression as a potential mechanism explaining the protective effects of Omegaven⢠and Ω3FA.MethodsHepG2 cells were cultured with each cytokine and Omegavenâ¢, or EPA and DHA, or Intralipidâ¢. P-Smad2/3 and PON1 protein levels were measured by Western blotting. ERK1/2 signaling was studied using homogenous time resolved fluorescence.ResultsOmegaven⢠decreased TGF-β mediated Smad2/3 signaling by 30% (70% of control ± 12, p < 0.03). Omegaven⢠decreased IL-1 and TNF-α mediated ERK1/2 signaling (0.49 fold ± 0.09, p < 0.05 and 0.22 ± 0.05, p < 0.05) compared to control.ConclusionOur results describe potential mechanisms by which Omegaven⢠and Ω3FA can be hepatoprotective in the setting of PNALD by abating inflammatory cytokine signaling.
Journal: Journal of Pediatric Surgery - Volume 52, Issue 6, June 2017, Pages 1020-1025