Endotoxin exposure alters brain and liver effects of fumonisin B 1 in BALB/c mice: Implication of blood brain barrier

Abstract

Fumonisin B 1 (FB 1), a mycotoxin produced by Fusarium verticillioides, causes equine leukoencephalomalacia and hepatotoxicity. We studied the modulation of FB 1 toxicity in brain and liver of female BALB/c mice after endotoxin administration to compromise the blood–brain barrier (BBB) integrity. Mice were injected intraperitoneally with saline or 3 mg/kg of lipopolysaccharide (LPS) followed 2 h later by either a single or three daily subcutaneous doses of 2.25 mg/kg of FB 1. After 4 h of a single FB 1 injection the inhibition of sphingolipid biosynthesis occurred in liver. Circulating alanine aminotransferase increased by LPS alone at this time. In brain LPS triggered inflammation increasing the expression of tumor necrosis factor (TNF) α, interferon (IFN) γ, interleukin (IL)-1β, IL-6, and IL-12; no effect of FB 1 was observed. In liver LPS + FB 1 attenuated the expression TNFα and IFNγ compared to LPS alone. One day after the 3-day FB 1 treatment the biosynthesis of sphingolipids was markedly reduced in brain and liver and it was further inhibited when LPS was given before FB 1. FB 1 induced hepatotoxicity, as measured by circulating liver enzymes, was reduced after the combined treatment with LPS + FB 1 compared to FB 1 alone. FB 1 decreased the LPS-induced brain expression of IFNγ and IL-1β, whereas the expression of IL-6 and IL-12 was augmented. In liver FB 1 also reduced the expression of IL-1β and IFNγ compared to LPS alone. Results indicated that endotoxemia concurrent with FB 1 intoxication facilitated the permeability of fumonisin in brain indicated by increased accumulation of sphinganine and endotoxin modified the effects of FB 1 in both brain and liver.