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ToxSci Advance Access published online on April 12, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj198
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Published by Oxford University Press 2006.
Received January 31, 2006
Accepted April 10, 2006

Systems Toxicology

Differential Sensitivity of Rat Kidney and Liver to Fumonisin Toxicity: Organ Specific Differences in Toxin Accumulation and Sphingoid Base Metabolism

Ronald T. Riley 1 * and Kenneth A. Voss 1

1 Toxicology and Mycotoxin Research Unit, USDA-ARS, Athens, GA 30604-5677

* To whom correspondence should be addressed.
Ronald T. Riley, E-mail: rriley{at}saa.ars.usda.gov


  Abstract

Fumonisins (FB) are mycotoxins in maize and are inhibitors of ceramide synthase (CS); the most likely proximate cause of FB toxicity. In liver and kidney, the primary target organs in FB fed rats, inhibition of CS results in a marked increase in the ceramide precursor sphinganine (Sa). This study was conducted to investigate the differential time- and dose-dependent changes in Sa, sphingosine (So), Sa-1-phosphate (Sa-1-P) and So-1-phosphate (So-1-P) in kidney, liver, serum and heart of male Sprague-Dawley rats (3-4 weeks old) fed diets containing 1.1, 13.5 and 88.6 µg/g of total FB for 10 days. The tissues were microscopically examined for the presence and severity of lesions consistent with FB exposure. There was a time- and dose-dependent increase in Sa in both liver and kidney that was closely correlated with the tissue concentration of FB1 and histopathologic findings. However, the Sa alone greatly under estimated the degree of disruption of sphingolipid metabolism since accumulated Sa and So were quickly metabolized to Sa-1-P and So-1-P as evidenced by large increases in these metabolites in kidney but not liver. The concentration of FB1 in liver and kidney that first elicited an increase in Sa was similar in both tissues, however, over time, the kidney accumulated significantly more FB1 (10X) and total Sa (Sa plus Sa-1-P) compared to liver. Thus, the relative sensitivity of male Sprague-Dawley rat kidney and liver is most likely a consequence of differences in the mechanisms responsible for both FB1 uptake/clearance and Sa metabolism.

Keywords: Fumonisin; Sphingolipids; Sphinganine; Sphinganine 1-phosphate; Sphingosine 1-phosphate.
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[Abstract] [Full Text] [PDF]


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