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Effects of cholestyramine on hepatic cholesterol 7α-hydroxylase and serum 7α-hydroxycholesterol in the hamster

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Lipids

Abstract

Cholestyramine increases activities of hepatic cholesterol 7α-hydroxylase and serum levels of 7α-hydroxycholesterol. To examine if serum 7α-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hamsters for 28 d in the dose-dependent study, and 2% cholestyramine for 0, 1, 3, 7, 14, 21, and 28 d in the time-dependent study. In the dose-dependent study, hepatic and serum cholesterol levels were significantly decreased dose-dependently when more than 0.5% of cholestyramine was fed for 28 d. Cholestyramine increased the cholesterol 7α-hydroxylase activity in a dose-dependent manner, while the serum 7α-hydroxycholesterol level was essentially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum cholesterol levels markedly decreased when 2% cholestyramine was fed for longer than 3 d. The serum triglyceride level increased significantly for the first 7 d and then decreased. Cholesterol 7α-hydroxylase activity increased significantly as early as day 1, reached maximum activity level on day 7, and then kept the significantly high values until day 28. The serum 7α-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7α-Hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7α-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7α-hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine.

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Abbreviations

DTT:

dithiothreitol

GC:

gas chromatography

GC-MS:

gas chromatography-mass spectrometry

LDL:

low density lipoprotein

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Authors and Affiliations

  1. Department of Surgery I, Kyushu University Faculty of Medicine, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Syoji Kuroki, Tokio Naito, Kazuo Chijiiwa & Masao Tanaka

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  1. Syoji Kuroki
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  2. Tokio Naito
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  3. Kazuo Chijiiwa
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  4. Masao Tanaka
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Correspondence to Syoji Kuroki.

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Kuroki, S., Naito, T., Chijiiwa, K. et al. Effects of cholestyramine on hepatic cholesterol 7α-hydroxylase and serum 7α-hydroxycholesterol in the hamster. Lipids 34, 817–823 (1999). https://doi.org/10.1007/s11745-999-0428-y

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  • DOI: https://doi.org/10.1007/s11745-999-0428-y

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