|Voss, Kenneth - Ken|
Submitted to: Revue de Medicine Veternaire
Publication Type: Review article
Publication Acceptance Date: 3/15/1998
Publication Date: N/A
Citation: Interpretive Summary: Fumonisin is a toxic chemical produced by molds that grow on and in corn. The fumonisins cause several animal diseases; including a lung disease in pigs and a brain disease in horses. In laboratory animals the fumonisins are toxic to both kidney and liver and are promoters of liver cancer in rats and rainbow trout. Epidemiological studies have found an association between consumption of fumonisin contaminated corn and both esophageal and liver cancer in human populations that are subsistence corn eaters. Numerous studies with animals have shown that the fumonisins cause changes in the way a unique type of fat called sphingolipids is metabolized. Fumonisin-induced changes in sphingolipid metabolism are closely correlated with changes in cell division and increased cell death and there is considerable evidence supporting the idea that changes in sphingolipid metabolism are the underlying cause of the fumonisin induced animal diseases. The health risk to American consumers is much less than to laboratory animals, since few Americans have diets that are primarily corn or corn products. Nonetheless, changes in sphingolipid metabolism are seen in laboratory animals that consume diets containing fumonisins at concentrations that have been found in U.S. corn for export and corn products on the grocers shelve. While the changes in sphingolipid metabolism occur with no evidence of animal toxicity, the health implications of subtle changes in the metabolism of these unusual fats are unknown.
Technical Abstract: The purpose of this article is to review the various mechanistic hypotheses for fumonisin-induced animal diseases; including porcine pulmonary edema, equine leukoencephalomalacia, nephrotoxicity and hepatotoxicity 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 increased cell death in most primary cell cultures and cell lines that have been examined. While primary rat hepatocytes and liver slices are very sensitive to fumonisin-induced disruption of sphingolipid metabolism, they are relatively insensitive to the toxic effects of fumonisins. Nonetheless, the onset and progression of F. moniliforme associated diseases in pigs, horses, rabbits, mice, and rats in vivo, are closely correlated with evidence for disruption of sphingolipid metabolism. Fumonisins also effect other aspects of lipid metabolism and sites of cellular regulation that are reportedly independent of the disruption of sphingolipid metabolism. However disruption of sphingolipid metabolism and signal transduction pathways, mediated by lipid second messengers or signaling pathways affected by disrupted sphingolipid metabolism, could be an important aspect of all the various proposed mechanisms of action.