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 i...
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Published in | Life sciences (1973) Vol. 63; no. 9; pp. 769 - 779 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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24.08.1998
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Abstract | 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. |
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AbstractList | 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. |
Author | Hébert, S Khalil, A Wallach, J Jay-Gerin, J P El Abbouyi, A Fortun, A Fülöp, Jr, T |
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SubjectTerms | Adult Antioxidants - pharmacology Chemotaxis - drug effects Cholesterol - metabolism Free Radicals - metabolism Humans Hydroxides - metabolism Lipid Peroxidation - drug effects Lipoproteins, LDL - metabolism Macrophages - drug effects Macrophages - metabolism Male Monocytes - drug effects Monocytes - physiology Oxidation-Reduction - drug effects Oxygen - metabolism Pregnatrienes - pharmacology |
Title | Novel 21-aminosteroid U-74389G inhibits low-density lipoprotein peroxidation induced by .OH and O2-. free radicals |
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