title: 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.
authors.affiliation: Department of Neurology, Medical Center of Central Massachusetts, Worcester 01605.
authors.forename: M
authors.initials: M
authors.lastname: Fisher
authors.forename: P H
authors.initials: PH
authors.lastname: Levine
authors.forename: E M
authors.initials: EM
authors.lastname: Doyle
authors.forename: M M
authors.initials: MM
authors.lastname: Arpano
authors.forename: J J
authors.initials: JJ
authors.lastname: Hoogasian
mesh_terms: D003300:Copper / Q000494:pharmacology*; D006801:Humans; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D011281:Pregnatrienes / Q000494:pharmacology*
chemical_list: D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D011281:Pregnatrienes; D003300:Copper; C053356:U 74500A