A 21-aminosteroid inhibits oxidation of human low density lipoprotein by human monocytes and copper.

Abstract:

:Oxidation of low density lipoprotein (LDL) leads to more rapid uptake by arterial wall macrophages and foam cell formation. Inhibiting LDL oxidation may impede these processes and offers a new mechanism to retard atherogenesis. The 21-aminosteroids, derived from methylprednisolone, are potent inhibitors of free radical production by stimulated monocytes and also are scavengers of lipid peroxyl radicals. The 21-aminosteroid, U74500A, was added to a mixture of low density lipoprotein cholesterol and human monocytes to which lipopolysaccharide was add to stimulate the monocytes. At a final concentration of 10 microM, U74500A reduced the production of lipid peroxidation from 6.10 +/- 1.11 to 0.84 +/- 0.16 nmol (mean +/- SEM) MDA equivalent/1 x 10(6) monocytes, as measured by a thiobarbituric acid reacting substance (TBARS) assay. Similarly 10 microns U74500A reduced Cu2+ induced LDL oxidation from 12.28 +/- 0.10 (in vehicle) to 0.49 +/- 0.12. These observations suggest that the 21-aminosteroids should be evaluated in animal models as a potential therapy to retard atherogenesis, especially considering their apparent lack of mineralocorticoid and glucocorticoid side-effects.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Fisher M,Levine PH,Doyle EM,Arpano MM,Hoogasian JJ

doi

10.1016/0021-9150(91)90115-j

subject

Has Abstract

pub_date

1991-10-01 00:00:00

pages

197-202

issue

2-3

eissn

0021-9150

issn

1879-1484

pii

0021-9150(91)90115-J

journal_volume

90

pub_type

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