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Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures.

Abstract：

:Using primary rat hepatocyte cultures, the potency of several garlic-derived organosulfur compounds to inhibit cholesterol biosynthesis in toto as well as at early and late steps of this metabolic pathway was compared. Concerning early steps, allicin significantly inhibited incorporation of [14C]acetate into nonsaponifiable neutral lipids already at concentrations as low as 10 microM, while diallyl disulfide and allyl mercaptan were effective above 100 microM only. Likewise, inhibition in response to the two vinyl-dithiins started at 500 microM. If [14C]acetate was replaced by [14C]mevalonate, inhibition due to allicin, diallyl disulfide, and allyl mercaptan disappeared suggesting that HMGCoA-reductase was the target of inhibition. In contrast, for the vinyl-dithiins a stimulation of mevalonate incorporation was found. Concerning the late step, the potency to exert accumulation of lanosterol presumably by inhibiting lanosterol 14 alpha-demethylase decreased in the order allicin > diallyl disulfide > allyl mercaptan = 1,3-vinyl-dithiin > 1,2-vinyldithiin, the effect of the latter compound being close to zero. With respect to the total inhibition of [14C]acetate labeling of cholesterol, the half-maximal effective concentration-value of allicin was determined to be 17 +/- 2 microM compared to 64 +/- 7 microM for diallyl disulfide and to 450 +/- 20 microM for allyl mercaptan. Cytotoxicity as determined by the lactate dehydrogenase leakage assay was slightly higher for the two vinyl-dithiins than for diallyl disulfide and allyl mercaptan, but was apparent only at concentrations higher than 10 mM and, consequently, was irrelevant for the effects described. These results demonstrate that different garlic-derived organosulfur compounds interfere differently with cholesterol biosynthesis and, thus, may provoke multiple inhibition of this metabolic pathway in response to garlic consumption. The fact that allicin was the most effective inhibitor argues against the possibility that its degradation products, namely diallyl disulfide or allyl mercapatan, might mediate its effects, a possibility that might be true, however, in the case of the vinyl-dithiins.

journal_name

Lipids

journal_title

Lipids

authors

Gebhardt R,Beck H

doi

10.1007/BF02587912

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

1269-76

issue

eissn

0024-4201

issn

1558-9307

journal_volume

pub_type

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Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures.