Fumonisin B1 consumption by rats causes reversible, dose-dependent increases in urinary sphinganine and sphingosine

Fumonisin B-1 (FB1) is a frequently encountered mycotoxin that inhibits ceramide synthase, the enzyme that acylates sphinganine, sphingosine and other "sphingoid" bases. Exposure of rats, rabbits, pigs and nonhuman primates to fumonisin-contaminated feed elevates sphingoid base amounts in urine; therefore, this study examined the time course and reversibility of these changes. When an AIN-76 diet supplemented with greater than or equal to 5 mu g FB1/g was fed to male Sprague-Dawley rats, there was a significant increase in sphinganine (ca. 50-fold in urine from rats fed 50 mu g FB1/g diet) and smaller changes in sphingosine within 5 to 7 d, compared to rats fed the same diet without FB1. No change occurred in sphingoid bases upon feeding 1 mu g FB1/g for up to 60 d. When rats were fed FB1 (10 mu g FB1/g diet: For 10 d), then changed to the same diet minus FB1, urinary sphingoid bases returned to normal within 10 d. However, if the rats were fed 10 mu g FB1/g for 10 d, then changed to 1 mu g FB1/g, the amounts of sphingoid bases in urine were the same as for rats that were continuously fed 10 mu g FB1/g. These results establish that consumption of FB1 causes dose-dependent and reversible elevations in the amounts of urinary sphingoid bases. The finding that 1 mu g FB1/g (which does not, alone, alter urinary sphingoid bases) will sustain the elevation caused by previous exposure to 10 mu g FB1/g raises the possibility that even low levels of fumonisins could be deleterious when an animal is occasionally exposed to higher amounts.