|Owens, Debra - USDA-APHIS, AMES, IA|
|Ross, P. - USDA-APHIS, AMES, IA|
Submitted to: Environmental Toxicology and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 21, 1997
Publication Date: N/A
Interpretive Summary: Fumonisin B1, B2 and B3 are toxic chemicals produced by fungi called Fusarium moniliforme and Fusarium proliferatum which are commonly found on corn. When animals eat the toxic chemical called fumonisin B1, there is a marked change in a group of fats (sphingolipids) which are very important to the normal function of cells. The changes which occur in cell function are suspected to be the cause of several animal diseases. One of these diseases is a brain disease in ponies (ELEM=equine leukoencephalomalacia). While all three toxic chemicals can occur on corn, the relative toxicity of the three is not known. The results of this study show that diets containing predominantly fumonisin B2, but not diets which were predominantly fumonisin B3, caused liver toxicity and the brain disease and that the relative toxicity was closely related to the changes in the sphingolipids. The results support the conclusion that fumonisin B2 and fumonisin B1 are more effective than fumonisin B3 in disrupting sphingolipid metabolism and induction of the brain disease and liver injury in ponies. If correct, this finding means that efforts to reduce the amount of fumonisins in corn when used in pony feeds should focus on fumonisin B1 and B2 and to a much lessor extent B3.
Technical Abstract: Fumonisin B1, B2, and B3 are inhibitors of ceramide synthase, a key enzyme in the pathway for de novo sphingolipid biosynthesis. Corn naturally contaminated with either predominantly fumonisin B1 or pure fumonisin B1 has been shown to cause equine leukoencephalomalacia (ELEM). It has been hypothesized that fumonisin-induced disruption of sphingolipid metabolism is an early event in the development of ELEM. Recently, it was shown that Fusarium proliferatum corn culture diets containing predominantly fumonisin B2, but not diets which were predominantly fumonisin B3, at 75 ppm (0.75 mg/kg BW/day) caused hepatotoxicity and ELEM. Analysis of free sphingoid bases and complex sphingolipids in serum, liver, and kidney, revealed that both the fumonisin B2 and B3 diets caused significant disruption of sphingolipid metabolism, however, the fumonisin B2 culture material diet was significantly more effective than the fumonisin B3 culture material diet at disrupting sphingolipid metabolism and in causing hepatotoxicity and clinical signs indicative of the onset of ELEM. A significant increase in the ratio of free sphinganine to free sphingosine in serum was first evident at day 4 and 11 with the fumonisin B2 and B3 diets, respectively. Increase in serum enzymes indicative of liver toxicity was first evident at day 34 in ponies fed the fumonisin B2 diet and clinical signs (head shaking, gait problems, and muscle tremors) were first observed at day 48. Ponies fed the fumonisin B3 diets showed no increase in serum enzymes or clinical signs for as long as 65 days when the study with fumonisin B3 was stopped. Results support the conclusion fumonisin B2 is more effective than fumonisin B3 in disrupting sphingolipid metabolism and induction of ELEM and liver injury in ponies.