Favism: Divicine hemotoxicity in the rat

David C. McMillan, David J. Jollow

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Favism is an acute hemolytic anemia known to occur in susceptible individuals who ingest fava beans. Susceptibility to favism is conferred by a genetic deficiency in erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity. Although the fava bean pyrimidine aglycones, divicine and isouramil, have been implicated in the onset of favism in humans, the lack of a well-defined experimental animal model for favism has hampered progress in elucidating the mechanism underlying hemotoxicity. We have examined whether a favic-like response could be provoked in G6PD-normal rats treated with synthetic divicine. Intraperitoneal administration of divicine to rats preloaded with 51Cr-tagged erythrocytes resulted in a severe, dose- dependent decrease in blood radioactivity (TD50 ~0.5 mmol/kg) within 24 h. The increased rate of removal of blood radioactivity was accompanied by a rapid decline in reduced glutathione levels in the blood, decreased hematocrits, marked hemoglobinuria, splenic enlargement, and reticulocytosis. In vitro exposure of 51Cr-tagged red cells to divicine before their re- administration to isologous rats also resulted in a sharp, concentration- dependent decrease in erythrocyte survival in vivo (TC50 ~1.5 mM), and these divicine-damaged red cells were removed from the circulation by the spleen. These data demonstrate that a favic response can be induced in G6PD- normal rats treated with divicine, and that hemolytic activity can be reproduced in isolated red cells under conditions that will allow a direct examination of the mechanism underlying this hemotoxicity.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalToxicological Sciences
Volume51
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Divicine
  • Erythrocytes
  • Favism
  • Glucose-6-phosphate dehydrogenase deficiency (G6PD)
  • Hemolytic anemia
  • Rat

ASJC Scopus subject areas

  • Toxicology

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