Grenier_2012_Biochem.Pharmacol_83_1465

Fumonisins are mycotoxins frequently found as natural contaminants in maize, where they are produced by the plant pathogen Fusarium verticillioides. They are toxic to animals and exert their effects through mechanisms involving disruption of sphingolipid metabolism. Fumonisin B(1) (FB(1)) is the predominant fumonisin in this family. FB(1) is converted to its hydrolyzed analogs HFB(1), by alkaline cooking (nixtamalization) or through enzymatic degradation. The toxicity of HFB(1) is poorly documented especially at the intestinal level. The objectives of this study were to compare the toxicity of HFB(1) and FB(1) and to assess the ability of these toxins to disrupt sphingolipids biosynthesis. HFB(1) was obtained by a deesterification of FB(1) with a carboxylesterase. Piglets, animals highly sensitive to FB(1), were exposed by gavage for 2 weeks to 2.8 mumol FB(1) or HFB(1)/kg body weight/day. FB(1) induced hepatotoxicity as indicated by the lesion score, the level of several biochemical analytes and the expression of inflammatory cytokines. Similarly, FB(1) impaired the morphology of the different segments of the small intestine, reduced villi height and modified intestinal cytokine expression. By contrast, HFB(1) did not trigger hepatotoxicity, did not impair intestinal morphology and slightly modified the intestinal immune response. This low toxicity of HFB(1) correlates with a weak alteration of the sphinganine/sphingosine ratio in the liver and in the plasma. Taken together, these data demonstrate that HFB(1) does not cause intestinal or hepatic toxicity in the sensitive pig model and only slightly disrupts sphingolipids metabolism. This finding suggests that conversion to HFB(1) could be a good strategy to reduce FB(1) exposure.