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, na turally contaminated with either predominantly fumonisin B-1 or pure f umonisin B-1, has been shown to cause equine leukoencephalomalacia (EL EM). It has been hypothesized that fumonisin-induced disruption of sph ingolipid metabolism is an early event in the development of ELEM. Rec ently, it was shown that Fusarium proliferatum corn culture diets cont aining predominantly fumonisin B-2, but not diets which were predomina ntly fumonisin B-3, at 75 ppm (0.75 mg/kg BW/day) caused hepatotoxicit y 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, h owever, 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 sig ns indicative of the onset of ELEM. A significant increase in the rati o of free sphinganine to free sphingosine in serum was first evident a t day 4 and 11 with the fumonisin B-2 and B-3 diets, respectively. Inc rease in serum enzymes indicative of liver toxicity was first evident at day 34 in ponies fed the fumonisin B-2 diet and clinical signs (hea d shaking, gait problems, and muscle tremors) were first observed at d ay 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 f umonisin B-3 was stopped. The results support the conclusion fumonisin B-2 is more effective than fumonisin B-3 in disrupting sphingolipid m etabolism and induction of ELEM and liver injury in ponies. (C) 1997 E lsevier Science B.V.