ABSTRACT
Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to -19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine.
Subject(s)
Aldehydes/pharmacokinetics , Diet, High-Fat , Fatty Acids, Omega-3/metabolism , Inflammation/metabolism , Intestinal Mucosa/metabolism , Oxidative Stress , Aldehydes/administration & dosage , Animals , Biomarkers/metabolism , Caco-2 Cells , Endoplasmic Reticulum Chaperone BiP , Glutathione Peroxidase/metabolism , Heat-Shock Proteins/metabolism , Humans , Intestinal Absorption/physiology , Lipid Peroxidation , Male , Mice , Mice, Inbred C57BL , Oxidation-ReductionABSTRACT
Several cases of delayed aortic rupture after endovascular aneurysm repair have been attributed to in vivo endograft fatigue. Such complications could involve damage to structural components during introduction. The purpose of this study was to compare forces applied during introduction to forces needed to damage the endograft. Testing was carried out on the custom-made endograft (CMEG) that has been in almost exclusive use at our center since 1996. Findings showed that the force applied during introduction was less than the force necessary to damage the endograft. No alteration in the mechanical properties of the CMEG was observed immediately after implantation.
