A Nominally Safe Dose of Fumonisins Induces Mild Neuroinflammation in Chickens by Targeting Sphingolipids and Oxylipins but Not Cytokines

Alterations in sphingolipids (SLs), oxylipins (OLs) and cytokines (CKs) are central to neuroinflammation. However, the effects of low doses Fumonisins B (FBs) on these analytes in the avian brain remain unclear.This study investigated SLs, OLs, CKs, and the activities of phospholipase A2c (PLA2c) and cyclooxygenase 2 (COX2) in the brains of chickens exposed to FB at a nominally safe dose of 14.6 mg FB1 + FB2/kg for 14 and 21 days. Targeted LC-MS/MS analyses revealed that FB exposure increased brain concentrations of sphingosine, N-acetyl-sphingosine, sphingosine 1-phosphate (So1P), ceramides (Cers), and sphingomyelins (SM). The Cer:SM ratio was elevated at 14 days but normalized by 21 days, whereas the So1P:Cer ratio rose at 14 days and continued to increase at 21 days. These changes coincided with elevated PLA2c and COX2 activities. OL profiling indicated a modest rise in pro-inflammatory arachidonic acid-derived COX metabolites at 14 days, while anti-inflammatory OLs derived from COX and lipoxygenase (LOX) pathways, including PGE2, 15-HETE, and 17-HDHA, increased significantly at 21 days. In contrast, the levels of CKs changed only slightly. Brain concentrations of Fumonisin B1 (FB1) indicated increased blood-brain barrier permeability.These findings highlight a key role of Cers in modulating OL production in FB neurotoxicity.