The liver metabolite S-422 of the hypolipidaemic drug benfluorex decreases cholesterol esterification in fibroblasts and monocyte-like cells.

Abstract:

:The effects of S-422 (1-(3-trifluoromethylphenyl)-2-[N-(2-hydroxyethyl) amino] propane), an hepatic metabolite of the hypolipidaemic drug Benfluorex, on lipid metabolism have been investigated in two experimental models: in human fetal lung fibroblasts, for study of the apo B/E receptor-mediated regulation of cholesterol metabolism, and in murine J 774 monocyte-like cells, for study of the scavenger receptor-mediated induction of cholesteryl ester accumulation. In human fibroblasts S-422 increased low density lipoprotein (LDL) catabolism by about 20%, whereas it decreased oleic acid incorporation into triacylglycerols and cholesteryl esters by 25 and 35%, respectively. In J 774 cells, S-422 decreased acetylated LDL degradation and cholesteryl ester formation by about 35%. In both cell types, ACAT activity was significantly reduced by the drug, either after a 24 h pretreatment of the cultured cells, or after an in vitro 30 min preincubation of cell homogenates. The results suggest that S-422, and thus Benfluorex, might prevent the development of atherosclerotic plaques.

journal_name

Eur J Clin Pharmacol

authors

Mazière JC,Mazière C,Auclair M,Mora L,Arnaud O

doi

10.1007/BF00314964

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

339-44

issue

4

eissn

0031-6970

issn

1432-1041

journal_volume

41

pub_type

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