FUMONISINS - MECHANISM OF MYCOTOXICITY

The purpose of this article is to review the various mechanistic hypot heses for fumonisin-induced animal diseases; including porcine pulmona ry edema, equine leukoencephalomalacia, nephrotoxicity and hepatotoxic ity in several animal species, and liver cancer promotion activity in rats. Disruption of sphingolipid metabolism is an early event that is closely correlated with alterations in cell proliferation and increase d cell death in most primary cell cultures and cell lines that have be en examined. While primary rat hepatocytes and liver slices are very s ensitive to fumonisin-induced disruption of sphingolipid metabolism, t hey are relatively insensitive to the toxic effects of fumonisins. Non etheless, the onset and progression of F. moniliforme-associated disea ses in pigs, horses, rabbits, mice, and rats in vivo, are closely corr elated with evidence for disruption of sphingolipid metabolism. Fumoni sins also affect other aspects of lipid metabolism and sites of cellul ar regulation that are reportedly independent of the disruption of sph ingolipid metabolism. However disruption of sphingolipid metabolism an d signal transduction pathways, mediated by lipid second messengers or signaling pathways affected by disrupted sphingolipid metabolism, cou ld be an important aspect of all the various proposed mechanisms of ac tion.