Differential effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis

OBJECTIVES This study was designed to examine the differential effects of a lpha- and gamma-tocopherol on parameters of oxidation-antioxidation and thr ombogenesis. BACKGROUND Experimental studies have shown that antioxidants, such as vitam in E (alpha-tocopherol), improve atherosclerotic plaque stability and vasom otor function, and decrease platelet aggregation and tendency to thrombus f ormation. METHODS Sprague Dawley rats were fed chow mixed with alpha- or gamma-tocoph erol (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. Th e aortic blood how was observed and continuously recorded using an ultrason ic Doppler flow probe. ADP-induced platelet aggregation, low-density lipopr otein oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes, superoxide anion generation and superoxide dismutase (SOD) act ivity were also measured. RESULTS Both alpha- and gamma-tocopherol decreased platelet aggregation and delayed time to occlusive thrombus (all p < 0.05 vs. control). Both alpha- and gamma-tocopherol decreased arterial superoxide anion generation, lipid peroxidation and LDL oxidation (all p < 0.05 vs. control), and increased e ndogenous SOD activity (p < 0.05). The effects of gamma-tocopherol were mor e potent than those of alpha-tocopherol (p < 0.05). CONCLUSIONS This study indicates that both alpha- and gamma-tocopherol decr ease platelet aggregation and delay intraarterial thrombus formation, perha ps by an increase in endogenous antioxidant activity. gamma-Tocopherol is s ignificantly more potent than alpha-tocopherol in these effects. (J Am Coll Cardiol 1999;34:1208-15) (C) 1999 by the American College of Cardiology.