| The first study determined the susceptibility of LDL to ex vivo oxidation and the subsequent cytotoxicity of the oxidized LDL (oxLDL) following consumption of oleate-, linoleate-, and EPA/DHA-supplemented diets. Fifteen postmenopausal women were given 15 g/d of oil supplements containing triglycerides rich in oleic acid, linoleic acid, and EPA and DHA in a three-period, three-treatment, crossover trial. Results showed that EPA/DHA-enriched LDL from human subjects produced fewer phosphatidylcholine hydroperoxides compared to oleate- and linoleate-enriched oxLDL after copper-induced oxidation ex vivo. The EPA/DHA treatment group had the lowest rate for the formation of conjugated dienes despite having the shortest lag time for conjugated diene formation. The results of measurement of cytotoxicity of the oxidized LDL showed no difference on the cell number or lactate dehydrogenase content of the cell medium in fibroblasts treated with these three types of fatty acid-enriched oxLDL. These findings suggest EPA/DHA-enriched LDL does not oxidize more readily than oleate- or linoleate-enriched LDL. Furthermore, EPA/DHA-enriched oxLDL is not more cytotoxic than oleate- or linoleate-enriched LDL.; The objective of the second study was to investigate the extent of apoptosis of a pro-monocytic cell line, U937, induced by EPA/DHA-enriched oxLDL, and to relate this activity to the lipid hydroperoxide production in EPA/DHA-enriched oxLDL. One healthy subject was given a 15 g/d supplement of fish oil for 5 weeks. Oxidative susceptibility of LDL was determined by measuring the formation of conjugated dienes and the accumulation of total cholesteryl ester hydroperoxides. OxLDL-induced cell apoptosis was confirmed by detecting the translocation of phosphatidylserine to the cell surface using the Annexin V-fluorescein isothiocyanate binding assay, chromatin condensation and nuclear fragmentation with the 4,6-diamidino-2-phenylindole staining assay, and activation of caspase-3. Results showed that LDL oxidative susceptibility tended to decrease and oxLDL-induced cell apoptosis decreased after fish oil supplementation. However, the percentage of cells undergoing apoptosis was not dependent on the concentration of cholesteryl ester hydroperoxides. (Abstract shortened by UMI.)... |
