Multiple emulsion-mediated enhancement of the therapeutic effect of tetrandrine against silicosis.
Chao-D-H; Ma-JYC; Malanga-CJ; Banks-DE; Hubbs-AF; Rojanasakul-Y; Castranova-V; Ma-JKH
Appl Occup Environ Hyg 1996 Jul; 11(7):1008-1018
The efficacy of tetrandrine contained within a multiple water/in oil/in water emulsion for treating silica (14808607) induced lung injury was studied in rats to test the hypothesis that tetrandrine emulsion by virtue of its specific targeting of alveolar macrophages (AMs) would show greater antifibrotic activity in silicosis than tetrandrine administered in solution. Male Sprague-Dawley-rats were injected intratracheally with 40 milligrams silica dust to induce experimental silicosis. They were then injected with 0 or 13mg/kg tetrandrine emulsion intravenously daily for 4 days. Other rats were similarly injected with tetrandrine in solution for comparison. The rats were killed 2 or 4 weeks (wk) after the last tetrandrine dose and the lungs were removed and weighed. The lungs were lavaged and lavagate cellularity was determined. Lung tissue samples were examined for histological changes. In untreated silicotic rats, the number and percentage of AMs in the lavagate were decreased at both time points and the proportion of inflammatory cells such as polymorphonuclear leukocytes (PMNs) was significantly increased. Tetrandrine emulsion restored the AM population to the control value and sharply reduced PMN influx into the lavagate as early as 2wk. Silica treatment sharply reduced resting and zymosan stimulated AM oxygen consumption. Tetrandrine emulsion restored this to the control values. AMs from silicotic rats contained phagocytized silica and lipid accumulations. AMs from tetrandrine emulsion treated rats showed little evidence of lipid accumulation. Tetrandrine emulsion countered the increases in lung weight and hydroxyproline content and development of lesions (granulomas and fibrosis) seen in silicotic rats. Tetrandrine administered in solution also showed similar beneficial effects but to a much smaller extent than tetrandrine emulsion. The authors conclude that multiple emulsions can enhance the antifibrotic activity of tetrandrine against silicosis.
NIOSH-Publication; NIOSH-Author; NIOSH-Grant; Pulmonary-system-disorders; Respiratory-system-disorders; Drug-therapy; Medical-treatment; In-vivo-studies; Laboratory-animals; Silica-dusts; Alveolar-cells; Lung-fibrosis
Joseph K. H. Ma, School of Pharmacy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 26506
Applied Occupational and Environmental Hygiene
Center to Protect Workers' Rights