No abstract

Fumonisins are potent inhibitors of sphingolipid biosynthesis produced by several Fusarium species. Consumption of corn or corn products infected with F. moniliforme, or high levels of fumonisins, is associated with several animal diseases. In a 4-wk feeding study, the concentration of fumonisin B1 that caused nephrotoxicity in Sprague-Dawley rats was much less than that required to cause hepatotoxicity. This retrospective study shows a close correlation between the extent and severity of ultrastructural lesions and the degree of disruption of sphingolipid metabolism. The kidney was more sensitive to fumonisin B1-induced disruption of sphingolipid metabolism than liver with significant elevation of free sphingosine, free sphinganine, and the free sphinganine:free sphingosine ratio in rats fed 15, 50 and 150 micrograms/g fumonisin B1. Accumulation of free sphinganine and elevation of the free sphinganine:free sphingosine ratio in urine closely reflected the changes that occurred in kidney. The accumulated sphinganine and elevation of the free sphinganine:free sphingosine ratio was associated with accumulation of cells in urine. Thus, urine rather than serum is the fluid of choice for detecting elevated free sphingoid bases generated as a consequence of fumonisin-induced kidney damage.

Fumonisins are metabolites of Fusarium moniliforme and other Fusarium spp. Fumonisin B1 (FB1) was hepatocarcinogenic (50 ppm, > or = 90% purity) when fed to male rats; however, neither the effects of FB1 on females nor the relationship between dietary FB1 levels and toxicity in rats has been reported. Male and female rats (three per sex per group) were fed diets fortified with 0, 15, 50 or 150 ppm FB1 (> or = 99% purity) for 4 weeks. There were no differences in general appearance or behavior among groups and significant differences in weight gain or food consumption were not found. Histopathological examinations and serum chemical profiles, including significant increases in triglycerides, cholesterol, and alkaline phosphatase, confirmed that 150 ppm FB1 was hepatotoxic to both sexes. Cortical nephrosis was found in males fed > or = 15 ppm and females fed > or = 50 ppm FB1. Both hepatic and renal lesions were consistent with those found in rats consuming F. moniliforme-infected corn. Thus, highly purified FB1 is unequivocally capable of inducing the subchronic liver and kidney lesions attributed to F. moniliforme.