Ezetimibe decreases serum oxidized cholesterol without impairing bile acid synthesis in Japanese hypercholesterolemic patients
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文摘

Objective

Cholesterol and diet-derived oxidized cholesterol are absorbed in the small intestine and eliminated by bile acids. We determined whether ezetimibe, a selective cholesterol absorption inhibitor, changes serum oxidized cholesterol levels.

Methods

We measured levels of plant sterols, cholesterol precursors, and oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics and 32 controls. Twenty-four hypercholesterolemics received 10?mg ezetimibe/day for 4 weeks.

Results

Plant sterols were 30-42 % higher in hypercholesterolemics than in controls and positively correlated with low-density lipoprotein-cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53 % , but did not change bile acid synthesis markers. 7¦Â-hydroxycholesterol, a marker for non-enzymatic oxidation of cholesterol, was 66 % higher in hypercholesterolemics than controls. Ezetimibe decreased 7¦Â-hydroxycholesterol levels by 15 % regardless of LDL-C reduction.

Conclusions

Ezetimibe decreases serum oxidized cholesterol generated by non-enzymatic reactions without impairing bile acid synthesis. Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet-derived oxidative burden.

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