The effects of fumonisin B1 at the No Observed Adverse Effect Level (NOAEL) and 5-times above on the renal histology and lipidome of rats

Food Chem Toxicol. 2022 Aug 18:113333. doi: 10.1016/j.fct.2022.113333. Online ahead of print.


Fumonisin B1 (FB1) mycotoxin was intraperitoneally (IP) administered at the No Observed Adverse Effect Level (NOAEL = 0.2 mg/kg BW/day as IP equivalent, "L") and 5-times above ("H") to male rats, in a controlled ("C"), 5-day study (n = 10/group, total n = 30). BW (bodyweight) of H rats decreased after day 4, kidney weight after 5 days. Renal histology revealed tubular epithelial desquamation, tubular dilatation, nuclear swelling, pale chromatin, cell vacuolation and casual karyopycnosis (H). Lipidomic analysis was performed with liquid chromatography - time-of-flight mass spectrometry (LC-TOF). Renal sphinganine (Sa) concentration increased 500 (L) to 1000-fold (H) and Sa-1-P to over 200 and 350-fold, respectively), with FB1 dose-dependence. Renal triacyclglycerols, diacylglycerols, ceramides and sphingomyelins were depleted, while cholesterol and cholesterol ester concentrations increased. Spearman correlation of free sphingoid bases (Sa, Sa-1-P, sphingosine (So) and So-1-P) was positive with histopathological damage severity, sphingomyelins and ceramides provided negative relationship (-0.78 and -0.8, resp.). Two-way cluster analysis and sparse partial least squares discriminant analysis (sPLS-DA) was used for experimental group classification. Fully effective group separation was achieved for ceramides, sphingomyelins and phosphatidyl-cholines, highlighting molecular species of possible diagnostic value. Lipidomic results highlight possible re-consideration of the NOAEL.

Keywords: Fumonisin B(1); Histopathology; Kidney; Lipidomics; Rat.