Identification of swainsonine as a probable contributory mycotoxin in moldy forage mycotoxicoses

When infested with the fungus Rhizoctonia leguminicola, certain forages, e.g., red clover hay, can cause a "slobber syndrome" of varying severity when consumed by ruminants. The causative agent has been presumed to be slaframine [(1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine], which is produced by R. leguminicola. In one serious outbreak of the slobber syndrome in horses, the red clover forage involved was carefully examined and found to contain R. leguminicola and slaframine. An identical hay sample is shown here by ion-exchange chromatographic and gas chromatographic-mass spectrometric analysis of appropriate hay extracts to also contain swainsonine [(1S,2R,8R,8aR)-1,2,8-trihydroxyoctahydroindolizine], a potent alpha-mannosidase inhibitor. Swainsonine has previously been isolated from pure cultures of R. leguminicola and from higher plants, namely the Darling pea (Swainsona canescens) and spotted locoweed (Astragalus lentiginosus). Consumption of Darling pea and spotted locoweed by livestock results in a severe neurological condition resembling that observed in hereditary mannosidosis in cattle and humans. Our findings indicate that swainsonine may be viewed as a mycotoxin when present in moldy forages consumed by livestock. The extent to which slaframine and swainsonine mycotoxicosis pose threats to animal husbandry and, indeed, to humans, if these alkaloids were to enter the human food chain, deserves serious consideration.