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-β-D-glucosaminidase, superoxide dis mutase, 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.
Original language | English |
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Pages (from-to) | 529-536 |
Number of pages | 8 |
Journal | Free Radical Biology and Medicine |
Volume | 24 |
Issue number | 4 |
DOIs | |
State | Published - Mar 1 1998 |
Keywords
- Free radical injury
- Inhibition of cytotoxicity
- Lazaroid protection
- Lipid peroxidation
- Silica-induced cytotoxicity prevention
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)