Efeito da vitamina E isolada e em associação com drogas redutoras do colesterol plasmatico sobre o perfil lipidico e a oxidação da lipoproteina de baixa densidade (LDL) em coelhos hipercolesterolemicos

AUTOR(ES)
DATA DE PUBLICAÇÃO

1997

RESUMO

Several lines of evidence suggest that oxidatively modified Low Density Lipoprotein (LDL) is atherogenic and that antioxidants may protect LDL against oxidation. Vitamin E is the main lipid-soluble antioxidant in human plasma and lipoproteins. The LDL-cholesterol levels are recognized as a primary risk factor for the development of atherosclerosis. Inhibitors of the rate-limiting enzyme of cholesterol 3-hydroxy-3-methyl- glutaryl coenzyme-A (HMG-CoA) reductase are now used to treat hypercholesterolemia. The purpose of this work was to study the effect and time course of vitamin E, pravastatin, simvastatin and vitamin E combined with pravastatin or simvastatin on the blood lipid profile and the lipid peroxidation of LDL in hypercholesterolemic rabbits. One hundred and thirty-six male, New Zealand white rabbits, weighing 2.0+0.1 kg, were randomly divided into 17 groups of 8 animals each: the normocholesterolemic group (NN) received a commercial non-purified rabbit diet; the hypercholesterolemic group (HH) received a diet enriched with cholesterol (5% w/w) for 30 days, and the 15 others groups received the same diet and the following treatments: supplementation with vitamin E (E-2, E-4, E-6 groups), pravastatin (P-2, P-4. P-6 groups), simvastatin (S-2, S-4, S-6 groups), vitamin E+pravastatin (PE-2, PE-4, PE-6 groups) and vitamin E+ simvastatin (SE-2, SE-4, SE-6 groups) during the last 2, 4, and 6 days of the experiment. Vitamin E (50 I.U./day), pravastatin (15 mg/day), simvastatin (10 mg/day), vitamin E (50 I.U./day) + pravastatin (15 mg/day) or vitamin E (50 I.U./day)+simvastatin (10 mg/day) were administered orally (intragastric tube). After the 30 days of study, a blood sample obtained by cardiac puncture was analyzed for plasma total cholesterol (TC), triacylglycerols (TG), HDL-cholesterol (HDL-c) by enzymatic methods. VLDL and LDL were isolated by ultracentrifugation. The extent of oxidation and the susceptibility of LDL to oxidation in vitro were measured by malonic dialdehyde (MDA) levels, estimated as thiobarbituric-acid reacting substances (TBARS). Results showed that total cholesterol, triacylglycerols, LDL-cholesterol (LDL-c) and VLDL-cholesterol (VLDL-c) levels were reduced in the groups of rabbits that received vitamin E for 6 days (p<0,05). TC/LDL-c and LDL-c/HDL-c ratios and composition of the LDL changed upon this time period. Rabbits in all groups treated with PE and SE showed lower TC and lipoproteins than those of others groups. TC and TG decreased in PE and SE groups after 4 days of treatment. LDL-c levels decreased in PE and SE groups at 2 and 4 days after treatment, respectively. HDL-c levels increased in PE-6 and SE-6 groups. Lipid composition of LDL was changed in PE-4 and SE-6 groups. The blood lipid profile changed in groups treated with pravastatin and simvastatin, during 4 days; TC, TG, VLDL-c and LDL-c were decreased. LDL isolated from those groups of rabbits under treatment with vitamin E were shown to be highly resistant to oxidative modification by cupric ions. MDA content of oxidized LDL were reduced by 75, 60, 55, 19 and 18% following treatment with E-6, PE-6, SE-6, P-6 and S-6, respectively. These data indicate that hypercholesterolemic rabbits treated with PE and SE confered significant protection to the LDL against oxidative modification in a short time, thus the association of hypocholesterolemic drugs with vitamin E being more effective than vitamin E alone. It is suggested that supplementing the diet of hypercholesterolemic rabbits with vitamin E may protect against the oxidation of LDL and could normalize the altered lipid profile of atherogenesis, thereby reducing the risk for coronary heart disease.

ASSUNTO(S)

colesterol vitamina e lipoproteinas

ACESSO AO ARTIGO

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