Effects of lovastatin therapy on susceptibility of LDL to oxidation duringalpha-tocopherol supplementation

Citation
A. Palomaki et al., Effects of lovastatin therapy on susceptibility of LDL to oxidation duringalpha-tocopherol supplementation, ART THROM V, 19(6), 1999, pp. 1541-1548
Citations number
66
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
10795642 → ACNP
Volume
19
Issue
6
Year of publication
1999
Pages
1541 - 1548
Database
ISI
SICI code
1079-5642(199906)19:6<1541:EOLTOS>2.0.ZU;2-I
Abstract
A randomized, double-masked, crossover clinical trial was carried out to ev aluate whether lovastatin therapy (60 mg daily) affects the initiation of o xidation of low density lipoprotein (LDL) in cardiac patients on alpha-toco pherol supplementation therapy (450 IU daily). Twenty-eight men with verifi ed coronary heart disease and hypercholesterolemia received alpha-tocophero l with lovastatin or with dummy tablets in random order. The two 6-week, ac tive-treatment periods were preceded by a washout period of at least 8 week s. The oxidizabilty of LDL was determined by 2 methods ex vivo. The depleti on times for LDL ubiquinol and LDL alpha-tocopherol were determined in time d samples taken during oxidation induced by 2,2-azobis(2,4-dimethylvaleroni trile). Copper-mediated oxidation of LDL isolated by rapid density-gradient ultracentrifugation was used to measure the lag time to the propagation ph ase of conjugated-diene formation. alpha-Tocopherol supplementation led to a 1.9-fold concentration of reduced alpha-tocopherol in LDL (P<0.0001) and to a 2.0-fold longer depletion time (P<0.0001) of cr-tocopherol compared wi th determinations after the washout period. A 43% prolongation (P<0.0001) w as seen in the lag time of conjugated-diene formation. Lovastatin decreased the depletion time of reduced alpha-tocopherol in metal ion-independent ox idation by 44% and shortened the lag time of conjugated-diene formation in metal ion-dependent oxidation by 7%. In conclusion alpha-tocopherol supplem entation significantly increased the antioxidative capacity of LDL when mea sured ex vivo, which was partially abolished by concomitant lovastatin ther apy.