Relative Effects of α- and γ-Tocopherol on Low-Density Lipoprotein Oxidation and Superoxide Dismutase and Nitric Oxide Synthase Activity and Protein Expression in Rats

Abstract

Background: Increasing evidence suggests that vitamin E prevents the progression of ath erosclerosis by inhibiting platelet aggregation, monocyte adhesion. and improving plaque stability and vasomotor function. Recently, controversy has arisen as to the relative effects of α- and γ-tocopherol in modulating some mediators of atherosclerosis. Methods and Results: We examined the effects of α- and γ-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 α- or γ-tocopherol (100 mg/kg/ day) for 7 to 10 days. Plasma α- and γ-tocopherol levels, low-density lipoprotein (LDL) oxida tion, and cNOS and SOD activity and protein expression were measured. Plasma α-tocopherol levels were significantly increased ( P < .01 vs control), but γ-tocopherol levels fell ( P < .01 vs control) in rats fed α-tocopherol. Plasma γ-tocopherol levels were increased ( P < .01 vs con trol), and α-tocopherol levels did not change in rats fed γ-tocopherol. Both α- and γ-tocopherol feeding decreased the rate of LDL oxidation induced by phorbol 12-myristate 13-acetate (PMA)-stimulated leukocytes ( P < .01 vs control). Both α- and γ-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 < .01 vs control). γ-Tocopherol was more potent than α-tocopherol in all these effects ( P < .05). Both a- and γ-tocopherol increased NO generation and cNOS activity (all P < .05 vs control). However, only γ-tocopherol increased cNOS protein expression. Conclusions: These observations indicate that whereas both α- and γ-tocopherol exert important effects on determinants of oxidation and vasomotor function, effects of dietary α-tocopherol supplementation in vivo are less pronounced than those of γ-tocopherol supplementation.