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Effects of a Novel Antihyperlipidemic Agent, S-2E, on the Blood Lipid Abnormalities in Homozygous WHHL Rabbits

Effects of a Novel Antihyperlipidemic Agent, S-2E, on the Blood Lipid Abnormalities in Homozygous WHHL Rabbits

K Ohmori, H Yamada, A Yasuda, A Yamamoto, N Matsuura, M Kiniwa

Metabolism. 2004 May;53(5):680-5.

PMID: 15131777

Abstract:

To improve mixed hyperlipidemia in the low-density lipoprotein (LDL) receptor-deficient state, suppression of very-low-density lipoprotein (VLDL) particle production may be an important approach. We previously reported that S-2E, (+)-(S)-p-[1-(p-tert-butylphenyl)-2-oxo-4-pyrrolidinyl] methoxybenzoic acid, suppressed VLDL particle production by inhibiting the biosynthesis of both sterol and fatty acids in the liver. We therefore examined whether S-2E lowered the blood cholesterol and triglyceride (TG) levels simultaneously in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, which correspond to human familial hypercholesterolemia. S-2E given orally at doses of 30 to 300 mg/kg significantly lowered serum total cholesterol (TC) levels at 1 week as well as TG at 2 weeks, and the lowering of TC and TG levels by S-2E reached a maximum at 3 to 4 weeks. In contrast, oral administration of pravastatin at doses of 10 to 100 mg/kg resulted in a significant suppression of TC levels (100 mg/kg) but not TG levels. Further analysis of the TC content in fractionated serum of control and S-2E-treated animals showed that suppression of TC level by S-2E is attributable to a decrease in the proportions of VLDL, intermediate-density lipoprotein (IDL), and LDL. It is, therefore, reasonable to assume that S-2E may be useful to improve the blood lipid abnormalities in the LDL receptor-deficient state.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP155730920	S-2E		155730-92-0	Price

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