Time- and dose-response effects of the mycotoxin, fumonisin B(1) on sphingoid base elevations in precision-cut rat...

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