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Liver Lipidomics, Histology, Transcriptomics, and Clinical Chemistry of Rats Intraperitoneally Treated with Fumonisin
András Szabó1,2, Mária Péter3, Gábor Balogh3
1Agribiotechnology and Precision Breeding for Food Security National Laboratory, Department of Physiology and Animal Health, Institute of Physiology and Nutrition, Hungarian University of Agriculture and Life Sciences, Kaposvár 7400, Hungary.
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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×.
