A 21-aminosteroid inhibits oxidation of human low density lipoprotein by human monocytes and copper
Department of Neurology
Copper; Humans; Lipid Peroxides; Lipoproteins, LDL; Monocytes; Oxidation-Reduction; Pregnatrienes
Molecular and Cellular Neuroscience | Neurology
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.
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Citation: Atherosclerosis. 1991 Oct;90(2-3):197-202.
Fisher, Marc; Levine, Peter H.; Doyle, Elizabeth M.; Arpano, Margaret M.; and Hoogasian, James J., "A 21-aminosteroid inhibits oxidation of human low density lipoprotein by human monocytes and copper" (1991). Neurology Publications and Presentations. 138.