Novel 21-aminosteroid U-74389G inhibits low-density lipoprotein peroxidation induced by .OH and O2−. free radicals

doi:10.1016/S0024-3205(98)00332-4

Life Sciences

Volume 63, Issue 9, 24 July 1998, Pages 769-779

https://doi.org/10.1016/S0024-3205(98)00332-4 Get rights and content

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 γ-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 α-tocopherol disappearance by about 47% at the concentration 20 μM. 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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Life Sciences

Novel 21-aminosteroid U-74389G inhibits low-density lipoprotein peroxidation induced by .OH and O2−. free radicals

Abstract

Free Radic. Biol. Med.

Atherosclerosis

J. Biol. Chem.

Atherosclerosis

Methods Enzymol.

FEBS Lett.

Biochim. Biophys. Acta.

Biochem. Med.

Methods Enzymol.

Biochem. Biophys. Res. Commun.

Biochem. Pharmacol.

Kidney Int.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Contribution of nitric oxide-dependent guanylate cyclase and reactive oxygen species signaling pathways to desensitization of μ-opioid receptors in the rat locus coeruleus

Novel synthesized aminosteroidal heterocycles intervention for inhibiting iron-induced oxidative stress

Enhancement of μ-opioid receptor desensitization by nitric oxide in rat locus coeruleus neurons: Involvement of reactive oxygen species

Nitric oxide consumption through lipid peroxidation in brain cell suspensions and homogenates

Age-related decrease of dehydroepiandrosterone concentrations in low density lipoproteins and its role in the susceptibility of low density lipoproteins to lipid peroxidation

Vitamin E protects neurons against oxidative cell death in vitro more effectively than 17-β estradiol and induces the activity of the transcription factor NF-κB

Novel 21-aminosteroid U-74389G inhibits low-density lipoprotein peroxidation induced by ^.OH and O₂^−. free radicals