Submitted to: Journal of Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 10/26/1998
Publication Date: N/A
Citation: Interpretive Summary: Fumonisins are toxic chemicals produced by molds that grow on and in corn. They cause several farm animal diseases. In laboratory and farm animals the fumonisins are toxic to both kidney and liver. The concentration of fumonisin that is commonly found in U.S. corn for export and corn products on the grocers shelves, is 1 to 2 parts per million (ppm). Studies with rats and rabbits have shown that at around 5 ppm, fumonisins cause changes in the way a unique type of fat (called sphingolipids) is metabolized. Fumonisin induced changes in sphingolipid metabolism are closely correlated with changes in cell behavior and the attachment sites for microbial pathogens and toxins. There is considerable evidence supporting the idea that changes in sphingolipid metabolism are the underlying cause of the fumonisin induced animal diseases. When the kidney is a target organ for fumonisin toxicity, the concentration of sphingolipids in urine increases. In this study with rats, animals that consumed diets containing fumonisin at 1 ppm showed no increase sphingolipids in the urine. However, rats that consumed fumonisin at a level that was toxic to the kidney (10 ppm), and were later changed to diets containing non-toxic fumonisin concentrations (1 ppm), the concentration of sphingolipids in the urine remain elevated. The results indicate that once affected, disruption of sphingolipid metabolism is easily maintained by the low level of fumonisin found in the U.S. corn. While the changes in sphingolipid metabolism can occur with no evidence of animal toxicity, the health implications of subtle and persistent changes in the metabolism of these unusual fats are unknown.
Technical Abstract: Fumonisin B1 (FB1) is a frequently encountered mycotoxin that inhibits ceramide synthase, the enzyme that acylates sphinganine, sphingosine, and other "sphingoid" bases. Exposure of rats, rabbits, pigs, and non-human primates to fumonisin-contaminated feed has been shown to elevate sphingoid base amounts in urine, therefore, this study examined the time course and reversibility of these changes using male Sprague-Dawley rats. When an AIN-76 diet supplemented with 1 micro-g FB1/g was fed for up to 60 days, there was no elevation in urinary sphingoid bases; however, both sphinganine and sphingosine increased significantly within 5 days when >5 micro-g FB1/g was fed, with the largest increases in sphinganine (ca 50-fold) with 50 micro-g FB1/g diet. FB1 also caused significant increases in sphingoid bases in kidney and liver. When rats were fed 10 micro-g FB1/g diet for 10 days and then changed to new diets, urinary sphingoid bases returned to normal within 10 days after the diet was changed to 0 micro-g FB1/g; however, urinary sphingoid bases remained elevated if the new diet contained 1 or 10 micro-gram FB1/g. These findings establish that consumption of FB1 reversibly elevates the amounts of sphingoid bases in urine. Furthermore, once urinary sphingoid bases are elevated, even low amounts (such as 1 micro-g FB1/g diet) sustain this elevation, which raises the possibility that innocuous amounts of fumonisins cause greater toxicity than would otherwise be predicted when there is occasional exposure to higher levels.