Liver Lipidomics, Histology, Transcriptomics, and Clinical Chemistry of Rats Intraperitoneally Treated with Fumonisin B1 for 5 days

Fumonisin B1 was intraperitoneally administered at 2.1
μg/animal/day
(1×) and 5 and 10 times above (5× and 10×) to male
rats for 5 days (n = 8/group, n =
32). Bodyweight gain decreased in all FB1-treated groups after 3 days,
while bodyweight decreased (10×) after 5 days. Feed intake and
liver weight decreased (5×, 10×). Clinical chemistry indicated
increased total protein, albumin, cholesterol, AST, ALT, and gamma-GT
(10×). Histopathology revealed apoptosis, mitosis, hydropic change,
mild steatosis, and pericentral glycogen depletion (10×). Shotgun
lipidomics showed an increase in sphingosine at 10×, with a dose-dependent
depletion of longer-chain ceramide and sphingomyelin molecular species.
GM3 ganglioside and free and esterified cholesterol increased linearly
with FB1 dose. Arachidonic acid (AA)-containing species of ether-type
phosphatidylcholine and phosphatidylethanolamine (PE) displayed a
linear dose response; those in diacyl PE and phosphatidylinositol
followed logarithmic models. Transcriptomics revealed downregulation
of steroid metabolism, while the NF-kB, sphingolipid, PI3K-Akt-PTEN,
and TNF signaling pathways were upregulated, critically beyond 5×.