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Antioxidant activity of lazaroid (U-75412E) and its protective effects against crystalline silica-induced cytotoxicity.

Authors
Huang-SH; Shi-SL; Goins-MR; Vallyathan-V
Source
Free Radic Biol Med 1998 Mar; 24(4):529-536
NIOSHTIC No.
20024992
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.
Keywords
Antioxidants; Silicates; Silica-dusts; Cytotoxicity; Pulmonary-disorders
Contact
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
CODEN
FRBMEH
Publication Date
19980301
Document Type
Journal Article
Fiscal Year
1998
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
0891-5849
NIOSH Division
HELD
Source Name
Free Radical Biology and Medicine
State
WV
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