Interaction of swainsonine with lymphoid and highly perfused tissues: a pharmacokinetics explanation for sustained immunomodulation.
The kinetics of inhibition of metastasis by the immunomodulator swainsonine (SW) is effective 1 to 3 days after administration. It is likely that SW's prolonged antimetastatic effect is due to its mitogenic property (spleenocytes isolated from animals treated with SW for 42-72 hours stimulated DNA synthesis that remained elevated for up to 3 days after removal of the drug from the drinking water). An analysis of SW in lymphoid (spleen and thymus) and highly perfused tissues was undertaken to determine if SW's sustained antimetastatic effect could be correlated to its retention. C57BL/6 mice received [3H]SW in drinking water for 24-72 hours and thereafter, received SW-free drinking for 24, 48, and 72 hours. Lymphoid and highly perfused tissues were analyzed for [3H]SW. At 24, 48, and 72 hours, spleen SW levels are, respectively, at least 2.33, 2.25, and 2.00 times greater than the perfused tissue; and thymus are, respectively, 1.44, 1.50, and 1.77 as great as the perfused tissue (kidney) with the highest SW level. These studies suggest that SW is predominantly retained for at least 72 hours, in lymphoid tissue. The targeting and retention of SW for lymphoid tissue days after removal of SW from animal drinking water is consistent with a) the immunomodulatory/mitogenic property and b) the sustained antimetastatic effect attributed to SW.
Bowen
D
D
Department of Pharmacology, Howard University College of Medicine, Washington, D.C. 20059, USA.
Southerland
W M
WM
Bowen
C D
CD
Hughes
D E
DE
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control; D013154:Spleen / Q000378:metabolism*; D017026:Swainsonine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013950:Thymus Gland / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; D014316:Tritium; D004247:DNA; D017026:Swainsonine