Fumonisin B₁ Consumption by Rats Causes Reversible, Dose-Dependent Increases in Urinary Sphinganine and Sphingosine

Manuscript received 17 February 1998. Initial reviews completed 15 May 1998. Revision accepted 26 October 1998.

Elaine Wang^*, Ronald T. Riley, Filmore I. Meredith, and Alfred H. Merrill Jr.^*,

^* Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA and  U. S. Department of Agriculture, Agriculture Research Service, Toxicology and Mycotoxins Research Unit, Athens, GA 30604-5677, USA

Fumonisin B₁ (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 5 µg 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 µg 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 µg FB₁/g for up to 60 d. When rats were fed FB₁ (10 µg 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 µg FB₁/g for 10 d, then changed to 1 µg FB₁/g, the amounts of sphingoid bases in urine were the same as for rats that were continuously fed 10 µg 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 µg FB₁/g (which does not, alone, alter urinary sphingoid bases) will sustain the elevation caused by previous exposure to 10 µg FB₁/g raises the possibility that even low levels of fumonisins could be deleterious when an animal is occasionally exposed to higher amounts.

The Journal of Nutrition Vol. 129 No. 1 January 1999, pp. 214-220
Copyright ©1999 by the American Society for Nutritional Sciences

This article has been cited by other articles:

				W. F. O. Marasas, R. T. Riley, K. A. Hendricks, V. L. Stevens, T. W. Sadler, J. Gelineau-van Waes, S. A. Missmer, J. Cabrera, O. Torres, W. C. A. Gelderblom, et al. Fumonisins Disrupt Sphingolipid Metabolism, Folate Transport, and Neural Tube Development in Embryo Culture and In Vivo: A Potential Risk Factor for Human Neural Tube Defects among Populations Consuming Fumonisin-Contaminated Maize J. Nutr., April 1, 2004; 134(4): 711 - 716. [Abstract] [Full Text] [PDF]

				C. Riebeling, J. C. Allegood, E. Wang, A. H. Merrill Jr., and A. H. Futerman Two Mammalian Longevity Assurance Gene (LAG1) Family Members, trh1 and trh4, Regulate Dihydroceramide Synthesis Using Different Fatty Acyl-CoA Donors J. Biol. Chem., October 31, 2003; 278(44): 43452 - 43459. [Abstract] [Full Text] [PDF]

				E. N. Enongene, R. P. Sharma, N. Bhandari, J. D. Miller, F. I. Meredith, K. A. Voss, and R. T. Riley Persistence and Reversibility of the Elevation in Free Sphingoid Bases Induced by Fumonisin Inhibition of Ceramide Synthase Toxicol. Sci., June 1, 2002; 67(2): 173 - 181. [Abstract] [Full Text] [PDF]

				Y. P. Dragan, W. R. Bidlack, S. M. Cohen, T. L. Goldsworthy, G. C. Hard, P. C. Howard, R. T. Riley, and K. A. Voss Implications of Apoptosis for Toxicity, Carcinogenicity, and Risk Assessment: Fumonisin B1 as an Example Toxicol. Sci., May 1, 2001; 61(1): 6 - 17. [Abstract] [Full Text] [PDF]