Novel 21-aminosteroid U-74389G inhibits low-density lipoprotein peroxidation induced by .OH and O2-. free radicals.
LDL peroxidation represents one of the first event in the atherogenesis process. Inhibiting LDL oxidation may impede this process and offers a new mechanism to retard atherogenesis. 21-Aminosteroids, derived from methylprednisolone, have recently excited much interest by virtue of their ability to inhibit lipid peroxidation. The aim of our work was to investigate the effect of a novel 21-aminosteroid, U-74389G, in the LDL peroxidation initiated in a metal- and cell-free system by oxygen free radicals, .OH and O2-., generated by water gamma-radiolysis. In a concentration dependent manner, U-74389G increased the resistance of LDL to oxidation measured by the length of the lag phase, reduced the formation of conjugated dienes and thiobarbituric acid-reactive substances (TBARS), and also reduced the alpha-tocopherol disappearance by about 47% at the concentration 20 microM. U-74389G was also able to reduce the chemotactic activity of oxidized LDL towards monocytes, as well as the cholesterol accumulation in macrophages. These observations suggest that the U-74389G is a potent antioxidant by decreasing LDL peroxidation and this should be evaluated in in vivo models as a potential therapy to retard atherogenesis.
Khalil
A
A
Laboratoire de Bio-Gérontologie, Centre de Recherche en Gérontologie, Institut Universitaire de Gériatrie, Sherbrooke, Québec, Canada.
Fortun
A
A
Hébert
S
S
Jay-Gerin
J P
JP
El Abbouyi
A
A
Wallach
J
J
Fülöp
T
T
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D011281:Pregnatrienes / Q000494:pharmacology*
D000975:Antioxidants; D005609:Free Radicals; D006878:Hydroxides; D008077:Lipoproteins, LDL; D011281:Pregnatrienes; C074965:U 74389F; C031356:hydroxide ion; D002784:Cholesterol; D010100:Oxygen