Effects of bisbenzylisoquinoline alkaloids on alveolar macrophages: correlation between binding affinity, inhibitory potency, and antifibrotic potential

Details

• Personal Author:
  Castranova, Vincent ; Kang H ; Ma JK ; Ma JY ; Malanga CJ ; Mo G ; Moore MD ; Schwegler-Berry D
• Description:
  The in-vitro effects of three bisbenzylisoquinoline alkaloids on the activation of alveolar macrophages by particles were investigated. The three alkaloids studied included tetrandrine (used in China as a treatment for silica induced pulmonary fibrosis), tubocurine (ineffective as an antifibrotic), and methoxyadiantifoline (unknown potency against fibrosis). The binding of these alkaloids to membrane lipid and alveolar macrophages was also examined and correlations between binding, inhibition of macrophage function, and/or antifibrotic potential were determined. Alveolar macrophages from male Sprague-Dawley-rats were treated with one of the alkaloids in-vitro, and cellular activity was measured. Pathogen free male Sprague-Dawley-rats were treated orally by gavage with tetrandrine at 33 micrograms/gram (microg/g) daily for 4 days. On the fifth day the rats were exposed to inhalation through either filtered air or silica (14808607) for 6 hours. After exposure the rats were returned to daily oral treatments with the drug for 4 more days and then sacrificed. Tetrandrine was a potent inhibitor of particle stimulated oxygen consumption, superoxide release and hydrogen- peroxide secretion by alveolar macrophages. Tetrandrine also exhibited substantial binding affinity for membrane lipids and alveolar macrophages. Tubocurine exhibited low binding affinity and had little effect on macrophage activation. Methoxyadiantifoline exhibited inhibitory and binding properties similar to those of tetrandrine. These findings support the usefulness of tetrandrine and methoxyadiantifoline as antifibrotic drugs. [Description provided by NIOSH]
• Subjects:
  Laboratories Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety Silicon Dioxide
• Keywords:
  Alveolar-cells In-vitro-studies In-vivo-studies Laboratory-animals Lung-cells Lung-fibrosis NIOSH-Author Respiratory-system-disorders Silica-dusts Silicosis
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  242-252
• Volume:
  108
• Issue:
  2
• NIOSHTIC Number:
  nn:00200088
• Citation:
  Toxicol Appl Pharmacol 1991 Apr; 108(2):242-252
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  1991
• NORA Priority Area:
  Pulmonary System Disorders
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b3df9449c9cb33559641ad2e8253675e2c3ff4c85e167372d545e11a917696e5b54ff3006eaaee1f4162f84c9844aadc90e54844c810b436b0f96266b53e980a
• Download URL:
  https://stacks.cdc.gov/view/cdc/204549/cdc_204549_DS1.pdf
• File Type:
  [PDF - 3.09 MB ]