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Ezetimibe Impairs Uptake of Dietary Cholesterol Oxidation Products and Reduces Alterations in Hepatic Cholesterol Metabolism and Antioxidant Function in Rats

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Lipids

Abstract

Dietary cholesterol oxidation products (COP) induce various adverse effects, including development of atherosclerosis, modulation of lipid metabolism, and unfavorable changes in the antioxidant system. Therefore, we examined the effects of ezetimibe, a cholesterol absorption inhibitor on hepatic cholesterol metabolism and down-regulation of the antioxidant system in rats fed COP. Rats were fed a purified diet containing 0.3 % COP with or without ezetimibe (0.07 mg/100 g body weight) for 27 days. Levels of COP in both the plasma and liver were lowered by ezetimibe through promotion of COP excretion into the feces. Reflecting this effect, an increase in the arteriosclerotic index and a reduction in the mRNA expression of hepatic cholesterol biosynthesis transcripts by dietary COP were observed. Moreover, the ferric reducing ability of the plasma also was significantly higher in rats fed COP plus ezetimibe than in those fed COP alone. Finally, we also observed that ezetimibe enhanced the down-regulation of hepatic fatty acid synthesis in rats fed COP. Thus, ezetimibe, which inhibits the absorption of dietary COP from the small intestine, may exert preventive effects on dietary COP-induced disruption of cholesterol and fatty acid metabolism in the liver and down-regulation of the antioxidant system.

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Abbreviations

BW:

Body weight

COP:

Cholesterol oxidation product

FAS:

Fatty acid synthase

FRAP:

Ferric reducing ability of plasma

G6PDH:

Glucose-6-phosphate dehydrogenase

GC:

Gas liquid chromatography

GC/MS:

GC–mass spectrometry

HDL:

High-density lipoprotein

HMG:

Hydroxymethylglutaryl

NPC1L1:

Niemann–Pick C1 like 1

RT-PCR:

Reverse transcription polymerase chain reaction

SREBP:

Sterol regulatory element-binding protein

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Authors and Affiliations

  1. Department of Agricultural Chemistry, School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa, 214-8571, Japan

    Shoichiro Terunuma, Noriko Kumata & Kyoichi Osada

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  1. Shoichiro Terunuma
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  2. Noriko Kumata
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  3. Kyoichi Osada
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Correspondence to Kyoichi Osada.

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Terunuma, S., Kumata, N. & Osada, K. Ezetimibe Impairs Uptake of Dietary Cholesterol Oxidation Products and Reduces Alterations in Hepatic Cholesterol Metabolism and Antioxidant Function in Rats. Lipids 48, 587–595 (2013). https://doi.org/10.1007/s11745-013-3790-6

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  • DOI: https://doi.org/10.1007/s11745-013-3790-6

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