|Voss, Kenneth - Ken|
Submitted to: Food and Chemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2001
Publication Date: 7/1/2001
Citation: Interpretive Summary: Fumonisins are poisons produced by a mold that is a common pathogen in corn. In rodents, fumonisins cause both liver and kidney cancer. One of the first things that fumonisin does to a cell is to change the way it makes a very unusual fat known as sphingolipids. When an animal eats corn that contains high levels of fumonisin there is a rapid increase in liver and kidney of a sphingolipid called sphinganine. All the toxic effects of the fumonisins seem to be very closely paralleled by changes in these unusual fats. Changes in these fats can be used to see if an animal has been exposed to fumonisins. This study used mice to show that the digestive tract is also a target for fumonisins. Mice were injected under the skin and then the cells in the digestive tract were removed and we looked for changes in the unusual fat that always goes up if fumonisins are in the cells. In the mice injected with fumonisin the fat first increased and then decreased. This change in the digestive tract paralleled the changes in the fat that occurred in the liver. However, in the kidney, the increased amounts of the fat were much more persistent. This study showed that the digestive tract and liver recover very quickly after exposure to fumonisin but that the kidney does not.
Technical Abstract: Fumonisins are mycotoxins produced by the fungus Fusarium moniliforme in corn. Fumonisin (FB) causes a increase in sphinganine (SA), the sphingoid base precursor in de novo biosynthesis of ceramide. High levels of SA in tissues is a biomarker for FB exposure. The liver and kidney are targets for ceramide synthase (CS) inhibition. This study determined if a subcutaneous injection of FB1 could cause an increase in sphingoid bases in the intestinal epithelial cells of BALB/c mice. It was hypothesized that since fumonisins are excreted in the bile following i.p. or i.v. administration, FB administered subcutaneously should also be excreted into the small intestines via bile and this should be detected by an elevation of sphingoid bases. Results of this study indicate that there is a significant time-dependent increase in SA in both the intestinal epithelia and liver that peaks at 4 to 8 h and declines to near the control level by 24 h. However, in kidney the increase in sphinganine was more persistent. The parallel time course of the change in SA in the intestinal epithelia and liver suggests that subcutaneously administered FB is rapidly excreted into the small intestines. Rapid cell turnover in the small intestines could account for the rapid reversal of the SA elevation. The rapid return to the control level in liver was unexpected since CS inhibition in cultured epithelial cells is persistent suggesting that liver handles either fumonisins or sphingoid bases quite differently than kidney.