DIETARY FUMONISIN B-1 INDUCES DISRUPTION OF SPHINGOLIPID METABOLISM IN SPRAGUE-DAWLEY RATS - A NEW MECHANISM OF NEPHROTOXICITY

Fumonisins are potent inhibitors of sphingolipid biosynthesis produced by several Fusarium species. Consumption of corn or corn products inf ected with F. moniliforme, or high levels of fumonisins, is associated with several animal diseases. In a 4-wk feeding study, the concentrat ion of fumonisin B-1 that caused nephrotoxicity in Sprague-Dawley rats was much less than that required to cause hepatotoxicity. This retros pective study shows a close correlation between the extent and severit y of ultrastructural lesions and the degree of disruption of sphingoli pid metabolism. The kidney was more sensitive to fumonisin B-1-induced disruption of sphingolipid metabolism than liver with significant ele vation of free sphingosine, free sphinganine, and the free sphinganine :free sphingosine ratio in rats fed 15, 50 and 150 mu g/g fumonisin B- 1. Accumulation of free sphinganine and elevation of the free sphingan ine: free sphingosine ratio in urine closely reflected the changes tha t occurred in kidney. The accumulated sphinganine and elevation of the free sphinganine:free sphingosine ratio was associated with accumulat ion of cells in urine. Thus, urine rather than serum is the fluid of c hoice for detecting elevated free sphingoid bases generated as a conse quence of fumonisin-induced kidney damage.