Chemical analysis and hemolytic activity of the fava bean aglycon divicine.
Divicine is an unstable aglycon metabolite of the fava bean pyrimidine beta-glucoside vicine. Divicine has long been thought to be a mediator of an acute hemolytic crisis, known as favism, in susceptible individuals who ingest fava beans (Vicia faba). However, a recent report has questioned the chemical identity of the divicine that was used in most of the studies on divicine hemotoxicity. The present study was undertaken to examine the hemolytic potential of synthetic divicine. Divicine was synthesized and its identity and purity were confirmed by HPLC, mass spectrometry, and NMR spectroscopy. The stability and redox behavior of divicine, under physiological conditions, were examined by HPLC and cyclic voltammetry. The data indicate that divicine is readily oxidized under aerobic conditions; however, it was sufficiently stable at pH 7.4 to permit its experimental manipulation. When 51Cr-labeled rat erythrocytes were exposed in vitro to the parent glucoside, vicine (5 mM), and then readministered to rats, no decrease in erythrocyte survival was observed. In contrast, erythrocyte survival was dramatically reduced by in vitro exposure to divicine (1.5 mM). These data demonstrate that divicine is a direct-acting hemolytic agent and thus may be a mediator of the hemolytic crisis induced by fava bean ingestion.
McMillan
D C
DC
Department of Pharmacology, School of Medicine, Medical University of South Carolina, Charleston 29425.
Schey
K L
KL
Meier
G P
GP
Jollow
D J
DJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004563:Electrochemistry; D004905:Erythrocyte Aging / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010946:Plants, Medicinal; D011744:Pyrimidinones / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014118:Toxins, Biological / Q000737:chemistry
D005960:Glucosides; D011744:Pyrimidinones; D014118:Toxins, Biological; C026511:divicine; C009661:vicine