Elevation of Sphinganine 1-Phosphate as a Predictive Biomarker for Fumonisin Exposure and Toxicity in Mice

Abstract

Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. An alteration in sphingolipid metabolism as a result of fumonisin B₁ (FB₁) exposure is related to cell death, and sphinganine/sphingosine ratio has been used as an indicator of fumonisin exposure in animals. The objective of this study was to investigate a new biochemical marker for the prediction of fumonisin-induced toxicity. When mice were treated with FB₁ (10 mg/kg ip/d) for 5 d, the serum levels of sphingoid bases and their 1-phosphate were markedly elevated. The accumulation of sphingosine 1-phosphate (So-1-P) and sphinganine 1-phosphate (Sa-1-P) in serum following FB₁ treatment was more apparent than elevated levels of sphingosine (So) and sphinganine (Sa). Sa-1-P/So-1-P ratio in serum was more elevated than Sa/So ratio following fumonisin B₁ treatment, indicating that phosphorylation of sphingoid bases may be a sensitive biomarker for fumonisin exposure. In addition, the tissue levels of Sa and Sa-1-P were also significantly elevated in kidneys, liver, heart, lung and brain. FB₁-induced toxicity was confirmed microscopically in both liver and kidneys. Liver lesions consisted of centrilobular hypertrophy and cytoplasmic vacuolization. In addition, hepatic binucleated cells were increased and acidophilic body was observed in FB₁-treated mice. Kidney lesions were consistent with tubular nephrosis, and tubules were dilated and contained cell debris in FB₁-exposed mice. These results suggested that the elevation of Sa-1-P as well as Sa in serum would be a specific biomarker for predicting FB₁ exposure, and elevated tissue levels of Sa-1-P may be related to fumonisin toxicity in animals.

Acknowledgements

This work was funded by Korea Science and Engineering Foundation (KOSEF) through grant R01-2002-000-00457-0.