Early fumonisin B1 toxicity in relation to disrupted sphingolipid metabolism in male BALB/c mice.
Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme, a common fungus in corn. It is known to cause a variety of diseases, including hepatic and renal degeneration in many species of laboratory and domestic animals. The known biochemical events in fumonisin B1 toxicity involve inhibition of ceramide synthase leading to disruption of sphingolipid metabolism. The effect of fumonisin B1 on ceramide and more complex sphingolipids in mice is not known. Groups of five male BALB/c mice each were injected with fumonisin B1 subcutaneously at doses of 0, 0.25, 0.75, 2.25, and 6.75 mg/kg body weight daily for 5 days. This protocol has been shown to produce a dose-dependent increase in apoptosis in liver and kidney of these animals. In the present study, liver, kidney, and brain were sampled and analyzed for free sphingoid bases and complex sphingolipids one day after the last treatment. A dose-related accumulation of free sphinganine and sphingosine was observed in liver and kidney, but not brain. The maximal increase in free sphinganine in kidney was 10-fold greater than in liver. Total phospholipids increased only in liver, whereas ceramide levels were not consistently altered in liver, kidney, or brain. In liver and kidney, fumonisin B1 treatment increased the sphinganine-containing complex sphingolipids, but no effect was observed on sphingosine-containing complex sphingolipids. No changes in complex sphingolipids were observed in brain. In liver, there was a close correlation between the extent of free sphinganine accumulation, and apoptosis and hepatopathy. This correlation was also evident in kidney but to a lessor extent. Nonetheless, the apoptosis and nephropathy occurred with little or no change in the levels of ceramide or more complex sphingolipids.
Tsunoda
M
M
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Sharma
R P
RP
Riley
R T
RT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002264:Carboxylic Acids / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002518:Ceramides / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D037341:Fumonisins; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009183:Mycotoxins / Q000633:toxicity; D010743:Phospholipids / Q000032:analysis; D013107:Sphingolipids / Q000032:analysis / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000032:analysis
D002264:Carboxylic Acids; D002274:Carcinogens, Environmental; D002518:Ceramides; D037341:Fumonisins; D009183:Mycotoxins; D010743:Phospholipids; D013107:Sphingolipids; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol