title: Dietary fumonisin B1 induces disruption of sphingolipid metabolism in Sprague-Dawley rats: a new mechanism of nephrotoxicity.
abstract: Fumonisins are potent inhibitors of sphingolipid biosynthesis produced by several Fusarium species. Consumption of corn or corn products infected with F. moniliforme, or high levels of fumonisins, is associated with several animal diseases. In a 4-wk feeding study, the concentration of fumonisin B1 that caused nephrotoxicity in Sprague-Dawley rats was much less than that required to cause hepatotoxicity. This retrospective study shows a close correlation between the extent and severity of ultrastructural lesions and the degree of disruption of sphingolipid metabolism. The kidney was more sensitive to fumonisin B1-induced disruption of sphingolipid metabolism than liver with significant elevation of free sphingosine, free sphinganine, and the free sphinganine:free sphingosine ratio in rats fed 15, 50 and 150 micrograms/g fumonisin B1. Accumulation of free sphinganine and elevation of the free sphinganine:free sphingosine ratio in urine closely reflected the changes that occurred in kidney. The accumulated sphinganine and elevation of the free sphinganine:free sphingosine ratio was associated with accumulation of cells in urine. Thus, urine rather than serum is the fluid of choice for detecting elevated free sphingoid bases generated as a consequence of fumonisin-induced kidney damage.
authors.affiliation: Toxicology and Mycotoxins Research Unit, USDA-ARS, Athens, GA 30613.
authors.forename: R T
authors.initials: RT
authors.lastname: Riley
authors.forename: D M
authors.initials: DM
authors.lastname: Hinton
authors.forename: W J
authors.initials: WJ
authors.lastname: Chamberlain
authors.forename: C W
authors.initials: CW
authors.lastname: Bacon
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: A H
authors.initials: AH
authors.lastname: Merrill
authors.forename: K A
authors.initials: KA
authors.lastname: Voss
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004032:Diet; D005260:Female; D037341:Fumonisins; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009183:Mycotoxins / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013107:Sphingolipids / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D037341:Fumonisins; D009183:Mycotoxins; D013107:Sphingolipids; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol