DISRUPTION OF SPHINGOLIPID METABOLISM IN NONHUMAN-PRIMATES CONSUMING DIETS OF FUMONISIN-CONTAINING FUSARIUM-MONILIFORME CULTURE MATERIAL

G. S. Shephard, L. van der Westhuizen, P. G. Thiel, W. C. A. Gelderblo m, W. F. O. Marasas and D. J. van Schalkwyk. Disruption of sphingolipi d metabolism in non-human primates consuming diets of fumonisin-contai ning Fusarium moniliforme culture material. Toxicon 34, 527-534, 1996. -The fumonisin mycotoxins are produced by Fusarium moniliforme Sheldon , a contaminant of corn worldwide. The two most abundant analogues (fu monisins B-1 and B-2) are known to be potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) and hence to disrupt de novo sp hingolipid biosynthesis. The sphingoid bases, sphingosine and sphingan ine (and hence their ratio), were measured at varying intervals over a period of 60 weeks in the serum of non-human primates (vervet monkeys ; Cercopithecus aethiops) which were consuming diets containing 'low' and 'high' amounts of F. moniliforme culture material, such that their total daily fumonisin intake was approximately 0.3 and 0.8 mg/kg body weight/day, respectively. Although no significant differences were fo und in the serum levels of sphingosine compared to controls, serum sph inganine levels in the experimental groups (mean of 219 nM and 325 nM, respectively) were significantly (P = 0.02) elevated above the levels in controls (mean 46 nM). As a consequence, the ratio sphinganine:sph ingosine was significantly (P = 0.003) elevated from a mean of 0.43 in the control group to 1.72 and 2.57 in the experimental groups, respec tively. Similar changes in sphingolipid profiles were also measured in urine with an increase of the ratio from 0.87 in controls to 1.58 and 2.17 in the experimental groups, although the differences were not st atistically significant. Hence, the disruption of sphingolipid biosynt hesis in vervet monkeys by fumonisins in culture material added to the ir diet can effectively be monitored in the serum as an elevation of t he sphinganine:sphingosine ratio. Copyright (C) 1996 Elsevier Science Ltd.