Relative effects of alpha-and gamma-tocopherol on low-density lipoprotein oxidation and superoxide dismutase and nitric oxide synthase activity and protein expression in rats.

BACKGROUND: Increasing evidence suggests that vitamin E prevents the progression of atherosclerosis by inhibiting platelet aggregation, monocyte adhesion, and improving plaque stability and vasomotor function. Recently, controversy has arisen as to the relative effects of alpha-and gamma-tocopherol in modulating some mediators of atherosclerosis.METHODS AND RESULTS: We examined the effects of alpha-and gamma-tocopherol on constitutive nitric oxide synthase (cNOS) and superoxide dismutase (SOD) activity and protein expression in rats. Sprague-Dawley rats were fed regular chow or chow mixed with alphaor gamma-tocopherol (100 mg/kg/day) for 7 to 10 days. Plasma alpha-and gamma-tocopherol levels, low-density lipoprotein (LDL) oxidation, and cNOS and SOD activity and protein expression were measured. Plasma alpha-tocopherol levels were significantly increased (eP [less than].01 vs control), but gamma-tocopherol levels fell (P [less than].01 vs control) in rats fed alpha-tocopherol. Plasma gamma-tocopherol levels were increased (P [less than].01 vs control), and alpha-tocopherol levels did not change in rats fed gamma-tocopherol. Both alpha-and gamma-tocopherol feeding decreased the rate of LDL oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes (P [less than].01 vs control). Both alpha-and gamma-tocopherol increased SOD activity in plasma and arterial tissues as well as Mn SOD and Cu/Zn SOD protein expression in arterial tissues (all P [less than].01 vs control). gamma-Tocopherol was more potent than alpha-tocopherol in all these effects (P [less than].05). Both a-and gamma-tocopherol increased NO generation and cNOS activity (all P [less than].05 vs control). However, only gamma-tocopherol increased cNOS protein expression. CONCLUSIONS: These observations indicate that whereas both alpha-and gamma-tocopherol exert important effects on determinants of oxidation and vasomotor function, effects of dietary gamma-tocopherol supplementation in vivo are less pronounced than those of gamma-tocopherol supplementation.

J Cardiovasc Pharmacol Ther. 1999 Oct; 4(4): 219-226