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Title: TIME DOSE RESPONSE EFFECTS OF THE MYCOTOXIN, FUMONISIN B1, ON SPHINGOID BASE ELEVATIONS IN PRECISION-CUT RAT LIVER AND KIDNEY SLICES

Author
item Norred, William
item Riley, Ronald
item Meredith, Filmore
item Bacon, Charles
item Voss, Kenneth

Submitted to: Toxicology In Vitro
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/3/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Fumonisin B1 is a toxin produced by some types of molds that can grow on corn. The toxins have been shown to cause illnesses in farm animals, including horses and pigs, and in laboratory rats and mice. Fumonisin appears to act in cells by blocking a key enzyme that is responsible for the formation of a group of important fats, namely sphingolipids. Sphingolipids are necessary components of all cells and carry out a number of important functions. Interference with their formation may be the mechanism of toxicity of fumonisin. In this study, we used thin slices of liver and kidney tissue obtained from laboratory rats to study the effects of fumonisin B1 on sphingolipids. Many of these slices can be obtained from only one rat. The results showed that the slices are very sensitive to the effects of fumonisin. Tissue slices could be a useful way to study the action of fumonisins, and to help identify whether there are other toxins produced by molds that act in a similar manner to fumonisins. They should also be useful to screen corn or corn-based products for the presence of fumonisins.

Technical Abstract: Fumonisins are mycotoxins produced on corn by the common fungus, Fusarium moniliforme. The fumonisins are potent inhibitors of sphingolipid biosynthesis, and cause dramatic elevations in the free sphingoid base, sphinganine (Sa), in both cells in culture and in urine, blood and tissues of animals dosed with the toxins. In this study the effects of fumonisin B1 (FB1) on sphingoid bases in precision-cut rat liver and kidney slices were evaluated. In liver slices exposed for 20 hr to FB1, as little as 0.1 uM caused a 40-fold elevation in free Sa. Kidney slices were less responsive, and a 1 uM dose of FB1 was required to cause a 10-fold increase in Sa. The amount of Sa in liver slices exposed to FB1 increased in a time dependent manner over a 72-hr period, but kidney slices exposed to the same doses of FB1 showed a peak elevation of Sa afer 24, with a decline in the levels over the next 48 hr. Liver slices may more closely approximate the in vivo response of animals to FB1 than do primary hepatocytes (in which Sa may be elevated >100-fold), because the elevations in Sa were similar to those reported in livers of animals fed fumonisins. On the other hand, the response of kidney slices to FB1 was substantially less than that reported in kidney tissue of FB1-fed rats, and suggests that kidney may accumulate toxic levels of sphingoid bases that are released from other tissues into the blood. The use of tissue slices also appears to be a useful bioassay tool for monitoring of corn or other products for toxins, such as fumonisins, that elevate Sa levels. Crude extracts of corn screenings naturally contaminated with fumonisins produced significantly elevated Sa levels in liver slices, even after 50-fold dilution of the extract.