The comparative pathology of the glycosidase inhibitors swainsonine, castanospermine and calystegines A3, B2 and C1 in mice

B. L. Stegelmeier, R. J. Molyneux, Robert J. Nash, Naoki Asano, Alison A. Watson

Research output: Contribution to journalArticlepeer-review

38 Citations (SciVal)

Abstract

To study various polyhydroxy-alkaloid glycosidase inhibitors, 16 groups of 3 mice were dosed using osmotic minipumps with swainsonine (0, 0.1, 1, and 10 mg/kg/day), castanospermine, and calystegines A3, B2, and C1 (1, 10, and 100 mg/kg/day). After 28 days, the mice were euthanized, necropsied, and examined using light and electron microscopy. The high-dose swainsonine?treated mice developed neurologic disease with neuro-visceral vacuolation typical of locoweed poisoning. Castanospermine- and calystegines-treated mice were clinically normal; however, high-dose castanospermine?treated mice had thyroid, renal, hepatic, and skeletal myocyte vacuolation. Histochemically, swainsonine- and castanospermine-induced vacuoles contained mannose-rich oligosaccharides. High-dose calystegine A3?treated mice had increased numbers of granulated cells in the hepatic sinusoids. Electron microscopy, lectin histochemistry, and immunohistochemistry suggest these are pit cells (specialized NK cells). Histochemically, the granules contain glycoproteins or oligosaccharides with abundant terminal N-acetylglucosamine residues. Other calystegine-treated mice were histologically normal. These findings indicate that swainsonine produced lesions similar to locoweed, castanospermine caused vacuolar changes with minor changes in glycogen metabolism, and only calystegine A3 produced minimal hepatic changes. These also suggest that in mice calystegines and castanospermine are less toxic than swainsonine, and as rodents are relatively resistant to disease, they are poor models to study such induced storage diseases.
Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalToxicologic Pathology
Volume36
Issue number5
DOIs
Publication statusPublished - 2008

Keywords

  • astragalus
  • castanospermine
  • locoweed
  • ipomoea
  • calystegine
  • swainsonine

Fingerprint

Dive into the research topics of 'The comparative pathology of the glycosidase inhibitors swainsonine, castanospermine and calystegines A3, B2 and C1 in mice'. Together they form a unique fingerprint.

Cite this