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Dietary Fumonisin B₁ Induces Disruption of Sphingolipid Metabolism in Sprague-Dawley Rats: A New Mechanism of Nephrotoxicity^1,2,3,

Toxicology and Mycotoxins Research Unit, USDA-ARS, P.O. Box 5677, Athens, GA 30613 ^* Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322

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 µg/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.

KEY WORDS: • fumonisins • kidney • rats • Fusarium • sphingolipids

¹ Supported by USDA-ARS funds and USDA-NRI competitive grant no. 91-37204-6684.

² Presented in part at the 32nd Annual Meeting of the Society of Toxicology, March 1993, New Orleans, LA [Riley, R. T., Hinton, D. M., Chamberlain, W. J., Bacon, C. W., Merrill, A. H., Jr., & Voss, K. A. (1993) Fumonisin (FB₁) inhibition of sphingolipid biosynthesis: a new mechanism of nephrotoxicity. Toxicologist 13: 133 (abs.)].

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ Authors to whom correspondence should be addressed.

Manuscript received 14 September 1993. Revision accepted 11 November 1993.

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