title: The low intestinal and hepatic toxicity of hydrolyzed fumonisin B₁ correlates with its inability to alter the metabolism of sphingolipids.
abstract: 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 B₁ (FB₁) is the predominant fumonisin in this family. FB₁ is converted to its hydrolyzed analogs HFB₁, by alkaline cooking (nixtamalization) or through enzymatic degradation. The toxicity of HFB₁ is poorly documented especially at the intestinal level. The objectives of this study were to compare the toxicity of HFB₁ and FB₁ and to assess the ability of these toxins to disrupt sphingolipids biosynthesis. HFB₁ was obtained by a deesterification of FB₁ with a carboxylesterase. Piglets, animals highly sensitive to FB₁, were exposed by gavage for 2 weeks to 2.8 μmol FB₁ or HFB₁/kg body weight/day. FB₁ induced hepatotoxicity as indicated by the lesion score, the level of several biochemical analytes and the expression of inflammatory cytokines. Similarly, FB₁ impaired the morphology of the different segments of the small intestine, reduced villi height and modified intestinal cytokine expression. By contrast, HFB₁ did not trigger hepatotoxicity, did not impair intestinal morphology and slightly modified the intestinal immune response. This low toxicity of HFB₁ correlates with a weak alteration of the sphinganine/sphingosine ratio in the liver and in the plasma. Taken together, these data demonstrate that HFB₁ does not cause intestinal or hepatic toxicity in the sensitive pig model and only slightly disrupts sphingolipids metabolism. This finding suggests that conversion to HFB₁ could be a good strategy to reduce FB₁ exposure.
authors.affiliation: INRA, UMR 1331 ToxAlim, Immuno-Myco-Toxicology Team, 180 Chemin de Tournefeuille BP 93173, 31027 Toulouse Cedex 3, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Grenier
authors.forename: Ana-Paula F L
authors.initials: AP
authors.lastname: Bracarense
authors.forename: Heidi Elisabeth
authors.initials: HE
authors.lastname: Schwartz
authors.forename: Catherine
authors.initials: C
authors.lastname: Trumel
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cossalter
authors.forename: Gerd
authors.initials: G
authors.lastname: Schatzmayr
authors.forename: Martine
authors.initials: M
authors.lastname: Kolf-Clauw
authors.forename: Wulf-Dieter
authors.initials: WD
authors.lastname: Moll
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D037341:Fumonisins / Q000633:toxicity*; D006868:Hydrolysis; D007422:Intestines / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D013107:Sphingolipids / Q000378:metabolism*; D013552:Swine
chemical_list: D017931:DNA Primers; D037341:Fumonisins; D013107:Sphingolipids; C056933:fumonisin B1