Submitted to: Journal of Biochemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/10/1997
Publication Date: N/A
Citation: N/A Interpretive Summary: Fumonisins are toxic chemicals produced by molds on corn. Because the fungus that produces the toxic chemical grows within the corn plant from the time it is a seed, these toxic chemicals are almost always found in corn. Occasionally, the amount of the toxic fumonisin in the corn can become quite high and cause the death of horses and pigs. We have discovered that when animals consume fumonisins, there is a change in the way that the liver, kidney, and lungs make fats. This is because the fumonisins interrupt a pathway of fat metabolism and cause certain very unusual fats to accumulate while some fats become depleted. It appears that some of the symptoms of the animal diseases are caused by these changes in fat metabolism. However, not all of the manifestations of the diseases can be explained by the changes in the fats. We have shown in mice that those tissues in which the fat changes are more pronounced, the cells die from a type of death that is referred to as "cell suicide". The relationship between the increased cell suicide and the presence of certain unique fats called sphingoid bases is very close. This work is significant because if we know the precise causes of the cell death, it is possible to develop treatments that can interrupt the process and lessen the damaging effects of the farm animal diseases.
Technical Abstract: 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 animal. 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 5 male BALB/c mice each were injected with fumonisin B1 subcutaneously at doses of 0, 0.25, 0.75, 2.25, 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 nof free sphinganine and sphingosine was observed in liver and kidney, but not brain. The maximal increase in free sphinganine in kidney was ten-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 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 levels of ceramide or more complex sphingolipids.