Strong Alterations in the Sphingolipid Profile of Chickens Fed a Dose of Fumonisins Considered Safe.

ABSTRACT

Fumonisins (FB) are mycotoxins known to exert most of their toxicity by blocking ceramide synthase, resulting in disruption of sphingolipid metabolism. Although the effects of FB on sphinganine (Sa) and sphingosine (So) are well documented in poultry, little information is available on their other effects on sphingolipids. The objective of this study was to analyze the effects of FB on the hepatic and plasma sphingolipidome in chickens. The first concern of this analysis was to clarify the effects of FB on hepatic sphingolipid levels, whose variations can lead to numerous toxic manifestations. The second was to specify the possible use of an alteration of the sphingolipidome as a biomarker of exposure to FB, in addition to the measurement of the SaSo ratio already widely used. For this purpose, we developed an UHPLC MS/MS method that enabled the determination of 82 SL, including 10 internal standards, in chicken liver and plasma. The validated method was used to measure the effects of FB administered to chickens at a dose close to 20 mg FB1 + FB2/kg feed for 9 days. Significant alterations of sphingoid bases, ceramides, dihydroceramides, glycosylceramides, sphingomyelins and dihydrosphingomyelins were observed in the liver. In addition, significant increases in plasma sphinganine 1-phosphate, sphingosine 1-phosphate and sphingomyelins were observed in plasma. Interestingly, partial least-squares discriminant analysis of 11 SL in plasma made it possible to discriminate exposed chickens from control chickens, whereas analysis of Sa and So alone revealed no difference. In conclusion, our results show that the effects of FB in chickens are complex, and that SL profiling enables the detection of exposure to FB when Sa and So fail.