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 |
Published |
Netherlands
24.08.1998
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Subjects | |
Online Access | Get full text |
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Summary: | 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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ISSN: | 0024-3205 |
DOI: | 10.1016/S0024-3205(98)00332-4 |