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

Abstract

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.