INRA, UMR 1331 ToxAlim, Immuno-Myco-Toxicology Team, 180 Chemin de Tournefeuille BP 93173, 31027 Toulouse Cedex 3, France.
Biochem Pharmacol. 2012 May 15;83(10):1465-73. doi: 10.1016/j.bcp.2012.02.007. Epub 2012 Feb 22.
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.
伏马菌素是一种真菌毒素,常作为玉米中的天然污染物,由植物病原体串珠镰刀菌产生。它们对动物有毒,通过干扰鞘脂代谢的机制发挥作用。伏马菌素 B₁(FB₁)是该家族中主要的伏马菌素。FB₁在碱性烹饪(煮制)或通过酶降解转化为其水解类似物 HFB₁。HFB₁的毒性记录很少,特别是在肠道水平。本研究的目的是比较 HFB₁和 FB₁的毒性,并评估这些毒素破坏鞘脂生物合成的能力。HFB₁是通过 FB₁与羧酸酯酶的酯解获得的。仔猪是对 FB₁高度敏感的动物,通过灌胃暴露于 2.8 μmol FB₁或 HFB₁/公斤体重/天 2 周。FB₁诱导肝毒性,如病变评分、几种生化分析物的水平和炎症细胞因子的表达所示。同样,FB₁损害了小肠的不同节段的形态,降低了绒毛高度并改变了肠道细胞因子的表达。相比之下,HFB₁没有引发肝毒性,没有损害肠道形态,并且轻微改变了肠道免疫反应。HFB₁的这种低毒性与肝脏和血浆中神经鞘氨醇/神经鞘氨醇比例的微弱改变相关。总之,这些数据表明 HFB₁在敏感的猪模型中不会引起肠道或肝毒性,并且仅轻微破坏鞘脂代谢。这一发现表明转化为 HFB₁可能是减少 FB₁暴露的一种好策略。