Increased accumulation of fumonisin B1, sphingoid bases and sphingoid base 1-phosphates: explaining the differential sensitivity of rat kidney and liver to fumonisin toxicity.

Authors: Riley, Ronald; Voss, Kenneth

Submitted to: Toxicological Sciences
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2006
Publication Date: 3/25/2007
Citation: Riley, R.T., Voss, K.A. 2007. Increased accumulation of fumonisin B1, sphingoid bases and sphingoid base 1-phosphates: explaining the differential sensitivity of rat kidney and liver to fumonisin toxicity. Toxicological Sciences. Abst. 1450, p. 200.

Interpretive Summary: Abstract - no summary required.

Technical Abstract: Fumonisins are mycotoxins in maize and inhibitors of ceramide synthase a key enzyme in the de novo sphingolipid biosynthesis pathway. In liver and kidney inhibition of ceramide synthase results in a marked increase in the ceramide precursor sphinganine. This study was conducted to investigate the differential changes in sphinganine, sphingosine, sphinganine-1-phosphate and sphingosine-1-phosphate in kidney, liver, serum and heart of male Sprague-Dawley rats fed diets containing fumonisins B1, B2 and B3 at a ratio of 1.00:0.45:0.10, respectively. The total fumonisins in the diets were 1.1, 13.5 and 88.6 Micro-g/g. Animals were killed after 1, 3, 5 and 10 days of feeding. The tissues were analyzed for sphingoid bases, sphingoid base 1-phosphates, and fumonisins B1, B2, and B3, and were microscopically examined for the presence and severity of lesions. Fumonisin B1, but not B2 or B3, was easily detected in liver, kidney and serum. There was a time- and dose-dependent increase in sphinganine in both liver and kidney that was closely correlated with the tissue concentration of fumonisin B1 and histopathologic findings. However, the sphinganine and sphingosine in kidney, but not liver, was quickly metabolized to sphinganine and sphingosine-1-phosphate. The concentration of fumonisin B1 in liver and kidney that first elicited an increase in sphinganine was similar in both tissues, however, over time, the kidney accumulated significantly more fumonisin B1 (10X) and total sphinganine (sphinganine plus sphinganine-1-phosphate). 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 fumonisin B1 uptake/clearance and sphinganine metabolism via the enzymes sphinganine kinase and sphinganine-1-phosphate lysase.