Antioxidant Activity of Lazaroid (U-75412E) and Its Protective Effects Against Crystalline Silica-Induced Cytotoxicity

Details

• Personal Author:
  Goins MR ; Huang SH ; Shi SL ; Vallyathan V
• Description:
  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. Description provided by NIOSH
• Subjects:
  • Aluminum Silicates
  • Antioxidants
  • Cytotoxins
  • Lipids
  • Lung
  • Occupational Health
  • Respiratory System
  • Safety
  • Silicon Dioxide
• Keywords:
  • Antioxidants
  • Silicates
  • Silica-dusts
  • Cytotoxicity
  • Pulmonary disorders
  • Author Keywords: Inhibition of cytotoxicity
  • Lazaroid protection
  • Silica-induced cytotoxicity prevention
  • Free radical injury
  • Lipid peroxidation
• ISSN:
  0891-5849
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  24
• Issue:
  4
• NIOSHTIC Number:
  nn:20024992
• Citation:
  Free Radic Biol Med 1998 Mar; 24(4):529-536
• Contact Point Address:
  Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  True
• Source Full Name:
  Free Radical Biology and Medicine
• Download URL:
  https://stacks.cdc.gov/view/cdc/196532/cdc_196532_DS1.pdf
• File Type:
  [PDF - 154.66 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:10c71205949d12c27b3d7ec82d51af6370f10e1a51e9bb0e22e625626b3c06e1227668188f62a4dccf836d67bbf3daafe90da546371780d7588459ccff81e7ff