EXPERIMENTAL STUDIES
Differential effects of  - and  -tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis
Tom Saldeen, MD, PhD, FACC ,
Dayuan Li, MD* and
Jawahar L. Mehta, MD, PhD, FACC*
* Department of Medicine, University of Florida, and VA Medical Center, Gainesville, Florida, USA
Department of Forensic Medicine, University of Uppsala, Uppsala, Sweden
Manuscript received October 6, 1998;
revised manuscript received May 12, 1999,
accepted June 25, 1999.
Reprint requests and correspondence: Dr. J.L. Mehta, Department of Medicine, University of Florida College of Medicine, 1600 Archer Road, P.O. Box 100277, JHMHC, Gainesville, Florida 32610.USA
mehta{at}medmac.ufl.edu
OBJECTIVES
This study was designed to examine the differential effects of  - and  -tocopherol on parameters of oxidation-antioxidation and thrombogenesis.
BACKGROUND
Experimental studies have shown that antioxidants, such as vitamin E (-tocopherol), improve atherosclerotic plaque stability and vasomotor function, and decrease platelet aggregation and tendency to thrombus formation.
METHODS
Sprague Dawley rats were fed chow mixed with - or -tocopherol (100 mg/kg/day) for 10 days. A filter soaked in 29% FeCl3 was applied around the abdominal aorta to study the patterns of arterial thrombosis. The aortic blood flow was observed and continuously recorded using an ultrasonic Doppler flow probe. ADP-induced platelet aggregation, low-density lipoprotein oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes, superoxide anion generation and superoxide dismutase (SOD) activity were also measured.
RESULTS
Both - and -tocopherol decreased platelet aggregation and delayed time to occlusive thrombus (all p < 0.05 vs. control). Both - and -tocopherol decreased arterial superoxide anion generation, lipid peroxidation and LDL oxidation (all p < 0.05 vs. control), and increased endogenous SOD activity (p < 0.05). The effects of -tocopherol were more potent than those of -tocopherol (p < 0.05).
CONCLUSIONS
This study indicates that both - and -tocopherol decrease platelet aggregation and delay intraarterial thrombus formation, perhaps by an increase in endogenous antioxidant activity. -Tocopherol is significantly more potent than -tocopherol in these effects.
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Abbreviations and Acronyms
| | ANOVA | = analysis of variance | | CAD | = coronary artery disease | | cNOS | = constitutive nitric oxide synthase | | LDL | = low density lipoprotein | | MDA | = malondialdehyde | | NO | = nitric oxide | | SOD | = superoxide dismutase | | t-PA | = tissue plasminogen activator |
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