Selenium supplementation acting through the induction of thioredoxin reductase and glutathione peroxidase protects the human endothelial cell line EAhy926 from damage by lipid hydroperoxides.

The human endothelial cell line EAhy926 was used to determine the importance of selenium in preventing oxidative damage induced by tert-butyl hydroperoxide (tert-BuOOH) or oxidised low density lipoprotein (LDLox). In cells grown in a low selenium medium, tert-BuOOH and LDLox killed cells in a dose-dependent manner. At 555 mg/l LDLox or 300 microM tert-BuOOH, >80% of cells were killed after 20 h. No significant cell kill was achieved by these agents if cells were pre-incubated for 48 h with 40 nM sodium selenite, a concentration that maximally induced the activities of cytoplasmic glutathione peroxidase (cyGPX; 5.1-fold), phospholipid hydroperoxide glutathione peroxidase (PHGPX;1.9-fold) and thioredoxin reductase (TR; 3.1-fold). Selenium-deficient cells pre-treated with 1 microM gold thioglucose (GTG) (a concentration that inhibited 25% of TR activity but had no inhibitory effect on cyGPX or PHGPX activity) were significantly (P<0.05) more susceptible to tert-BuOOH toxicity (LC(50) 110 microM) than selenium-deficient cells (LC(50) 175 microM). This was also the case for LDLox. In contrast, cells pre-treated with 40 nM selenite prior to exposure to GTG were significantly more resistant to damage from tert-BuOOH and LDLox than Se-deficient cells. Treatment with GTG or selenite had no significant effect on intracellular total glutathione concentrations. These results suggest that selenium supplementation, acting through induction of TR and GPX, has the potential to protect the human endothelium from oxidative damage.

Do oxidized fatty acids activate coagulation factor VII during post-prandial lipemia in women?

Factor VII is activated to VIIa within hours after dietary fat, irrespective of its fatty acid composition. Edible oils contain oxidized material (hydroxy fatty acids, HOFA). Twenty-five fasting women, aged 38 (10) years, consumed 30 g walnut oil containing 26 (6) mg HOFA. Blood was collected 2-hourly to measure plasma triglycerides and plasma lipid HOFA by gas chromatography/mass spectrometry. VII and sTF-dependent VIIa were quantified at 0, 6 and 24 h. Increased plasma triglycerides and HOFA (areas under the curve 0-8 h, AUC) were related r = 0.83, p < 0.001. VIIa increased from 2.6 (1.4) to 4.2 (1.9) ng/mL at 6 h (p < 0.001). Plasma VII remained constant. VIIa (6 h) was related to plasma triglycerides- and HOFA-AUC: r = 0.38 and 0.53, respectively (both p < 0.05). Plasma VIIa was also related to body weight, fasting triglycerides, HOFA and VII. Only HOFA-AUC and body weight related to VIIa (6 h) in stepwise regression analysis (p = 0.007 and 0.038, respectively). Oxidized, not normal, fat activates VII and could increase coronary risk in humans.