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  • Title: Antioxidant activity of lazaroid (U-75412E) and its protective effects against crystalline silica-induced cytotoxicity.
    Author: Huang SH, Leonard S, Shi X, Goins MR, Vallyathan V.
    Journal: Free Radic Biol Med; 1998 Mar 01; 24(4):529-36. PubMed ID: 9559864.
    Abstract:
    Lazaroids (21-amino steroids) are believed to be powerful scavengers of reactive oxygen species (ROS) and inhibitors of lipid peroxidation. Crystalline silica, a potent cytotoxic agent, causes pulmonary fibrosis in experimental animals and humans. ROS have been previously shown to be involved in crystalline silica-induced pulmonary injury and inflammation. In the present study, the reaction rate of lazaroid (U-75412E) with hydroxyl radical (.OH) generated by Fenton reaction (Fe(II) + H2O2 --> Fe(III) + OH- + .OH) was investigated using ESR spin-trapping competition reactions. The reaction rate constant was found to be 1.0 x 10(10) M(-1)s(-1), which was comparable with those of other efficient .OH radical scavengers. As indicators of crystalline silica-induced cytotoxicity and its protection by this antioxidant lazaroid (U-75412E) we measured lactate dehydrogenase, N-acetyl-beta-glucosaminidase, superoxide dismutase, glutathione peroxidase, and hydrogen peroxide released from rat alveolar macrophages. Lipid peroxidation, a prominent manifestation of .OH radical-induced cell injury, was also measured to evaluate the protective value of lazaroid. Alveolar macrophages treated with lazaroid (U-75412E) before crystalline silica exposure were protected against cell injury and lipid peroxidation as demonstrated by those indicators. Lazaroid (U-75412E) scavenges .OH radicals generated by crystalline silica-mediated reaction from H2O2 and inhibits lipid peroxidation in macrophages induced by these particles.
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