N-3 PUFA Supplementation Triggers PPAR-α Activation and PPAR-α/NF-κB Interaction: Anti-Inflammatory Implications in Liver Ischemia-Reperfusion Injury

摘要: Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) to rats preconditions liver against ischemia-reperfusion (IR) injury, reduction of enhanced nuclear factor-κB (NF-κB) functionality occurring in early phase IR recovery IR-induced pro-inflammatory cytokine response. The aim present study was test hypothesis that preconditioning by PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α) activation interference NF-κB activation. For this purpose we evaluated formation PPAR-α/NF-κBp65 complexes relation changes PPAR-α activation, IκB-α phosphorylation serum levels expression interleukin (IL)-1β tumor necrosis factor (TNF)-α a model hepatic IR-injury (1 h ischemia 20 reperfusion) or sham laparotomy (controls) male Sprague Dawley rats. Animals were previously supplemented for 7 days encapsulated fish oil (General Nutrition Corp., Pittsburg, PA) isovolumetric amounts saline (controls). Normalization IR-altered parameters injury (serum transaminases morphology) achieved dietary supplementation. EPA DHA suppression paralleled generation complexes, concomitance normalization phosphorylation. evidenced enhancement PPAR-α-regulated Acyl-CoA oxidase (Acox) Carnitine-Palmitoyl-CoA transferase I (CPT-I) genes. Consistent these findings, NF-κB-controlled cytokines IL-lβ TNF-α observed at reperfusion. Taken together, findings point an antagonistic effect on transcription mediators. This associated cytosolic stability, as major mechanisms induced injury.