Effect of homocysteine, folates, and cobalamin on endothelial cell- and copper-induced LDL oxidation.
Oxidation of LDL contributes to endothelial 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 endothelial 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 endothelial 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 peroxidation, 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.
Ronco
Ana María
AM
Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Casilla 138-11, Santiago, Chile. amronco@inta.cl
Garrido
Argelia
A
Llanos
Miguel N
MN
Guerrero-Bosagna
Carlos
C
Tamayo
Daniela
D
Hirsch
Sandra
S
D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005492:Folic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D012016:Reference Values; D014471:Umbilical Veins; D014805:Vitamin B 12 / Q000494:pharmacology*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006710:Homocysteine; C032418:5,11-methenyltetrahydrohomofolate; D003300:Copper; D005492:Folic Acid; D014805:Vitamin B 12