Effect of homocysteine, folates, and cobalamin on endothelial cell- and copper-induced LDL oxidation

Oxidation of LDL contributes to enclothelial dysfunction and atherosclerosis. This process could be associated with hyperhomocysteinemia, a condition that can be reduced after folic acid treatment. Because a reduction in LDL oxidation may improve enclothelial function, we studied the effect of some vitamins (folic acid, 5-methyltetrahydrofolic acid, and vitamin B-12) on LDL oxidation, either in the presence or absence of homocysteine. For this purpose, two in vitro systems were used: an enclothelial cell-catalyzed LDL oxidation system and a cell-free copper-initiated LDL oxidation system. The kinetics of copper-catalyzed LDL oxidation was determined by continuous monitoring of the production of conjugated dienes in the reaction medium. TBARS production, a parameter of lipid peroxiclation, was also evaluated. In both in vitro systems, only 5-methyltetrahydrofolic acid was able to decrease TBARS production in a concentration-dependent manner, independently of the presence or absence of homocysteine. In the copper-induced LDL oxidation system, vitamin B-12 and 5-methyltetrahydrofolic acid increased the lag time of conjugated diene production by 25 and 47%, respectively, suggesting that both vitamins in this system had antioxidant properties. Folic acid was unable to show antioxidant properties when included in either in vitro system. The results demonstrate that 5-methyltetrahydrofolic acid and vitamin B-12 are important protective agents against LDL oxidative modifications.