Disruption of Sphingolipid Metabolism in Small Intestines, Liver and Kidney of Mice Dosed Subcutaneously with Fumonisin B(1)

Fumonisin B(1) is a fungal inhibitor of ceramide synthase, a key enzyme in the de novo biosynthesis of sphingolipids. The resulting increase in tissue free sphinganine (and sometimes sphingosine) is used as a biomarker for fumonisin exposure. This study determined whether a single subcutaneous injection of fumonisin B(1) could cause an increase in free sphingoid bases in the intestinal epithelial cells of mice over 24 hr. It was hypothesized that fumonisin administered subcutaneously would be excreted into the small intestine via biliary excretion, and this should be detectable by increased sphingoid bases in the intestine. A significant time-dependent increase in sphingoid bases occurred in the intestine and liver peaking at 4-8 hr and declining to control levels by 24 hr. In the kidney the increase in free sphinganine was persistent. The parallel time course of the change in sphinganine in the intestine and liver suggested fumonisin B(1) was rapidly excreted into the small intestine. Rapid cell turnover in the intestine could account for the reversal of the sphinganine increase. The rapid return to the control level in liver was unexpected since ceramide synthase inhibition in cultured cells is persistent suggesting that liver handles fumonisin B(1) or sphingoid bases quite differently than kidney.