Effects of bisbenzylisoquinoline alkaloids on alveolar macrophages: Correlation between binding affinity, inhibitory potency, and antifibrotic potential.
Castranova-V; Kang-H; Ma-JK; Mo-G; Malanga-CJ; Moore-MD; Schwegler-Berry-D; Ma-JY
Toxicol Appl Pharmacol 1991 Apr; 108(2):242-252
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.
NIOSH-Author; Respiratory-system-disorders; Alveolar-cells; Lung-cells; Silica-dusts; Silicosis; Laboratory-animals; Lung-fibrosis; In-vivo-studies; In-vitro-studies
Toxicology and Applied Pharmacology