Disruption of sphingolipid metabolism and induction of equine leukoencephalomalacia by Fusarium proliferatum culture material containing fumonisin B(2) or B(3).

Fumonisin B(1), B(2), and B(3) are inhibitors of ceramide synthase, a key enzyme in the pathway for de novo sphingolipid biosynthesis. Corn, naturally contaminated with either predominantly fumonisin B(1) or pure fumonisin B(1), 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 B(2), but not diets which were predominantly fumonisin B(3), 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 B(2) and B(3) diets caused significant disruption of sphingolipid metabolism, however, the fumonisin B(2) culture material diet was significantly more effective than the fumonisin B(3) 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 B(2) and B(3) diets, respectively. Increase in serum enzymes indicative of liver toxicity was first evident at day 34 in ponies fed the fumonisin B(2) diet and clinical signs (head shaking, gait problems, and muscle tremors) were first observed at day 48. Ponies fed the fumonisin B(3) diets showed no increase in serum enzymes or clinical signs for as long as 65 days when the study with fumonisin B(3) was stopped. The results support the conclusion fumonisin B(2) is more effective than fumonisin B(3) in disrupting sphingolipid metabolism and induction of ELEM and liver injury in ponies.