TOXICITY AND SPHINGANINE LEVELS ARE CORRELATED IN RATS FED DIETS PROVIDING FUMONISIN B1 (FB1) OR HYDROLYZED FB1 (HFB1)

Authors: Voss, Kenneth; Riley, Ronald; Bacon, Charles; Meredith, Filmore; Norred, William

Submitted to: Environmental Toxicology and Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Fusarium molds are found on corn. They produce fumonisins, mycotoxins which cause animal disease and have been linked to cancer in man. Fumonisins block the enzyme ceramide synthetase. This block increases tissue sphinganine concentration and is believed to be the key step leading to toxicity. Hydrolyzed fumonisins are found in masa flour, the main ingredient of tortillas. Masa is made by nixtamalizing corn, a process which converts fumonisins to hydrolyzed fumonisins. We fed diets containing equal amounts of a) moldy corn (CM diet), b) nixtamalized moldy corn (NX diet), c) water-extracted moldy corn (WE diet), or control diet (SC diet) to rats. The CM and WE diets contained 9.8 and 1.1 nmol/g and fumonisin B1. The NX diet contained 14.3 nmol/g hydrolyzed fumonisin B1, but no fumonisin B1. Liver and kidney toxicity and increased sphinganine concentrations were found in the NX group, but to a significantly lesser extent than in the CM diet group. Regardless of diet, a close correlation between toxic effects and tissue sphinganine levels, and thus ceramide synthetase blockage, was found. These findings indicate that liver and kidney disease caused by hydrolyzed fumonisins, like those caused by fumonisins, are related to inhibition of ceramide synthetase and provide additional, strong evidence for the central role of sphingolipid metabolism in the onset of animal illness related to fumonisins and fumonisin-like compounds.

Technical Abstract: Fumonisins are mycotoxin produced by Fusarium species commonly found on corn, cause species-specific toxicoses, and have been linked to esophageal cancer in man. Fumonisin B1 (FB1) inhibits ceramide synthetase, increasing tissue sphinganine concentrations (Sa) and sphinganine to sphingosine (So) ratios (Sa/So). Nixtamalization, a hydrolytic process for producing masa flour, converts FB1 to hydrolyzed FB1 (HFB1) but does not qualitatively alter the toxicity of fumonisin B1 (FB1)-containing F. moniliforme culture material (CM) in rats. Rats were fed diets containing nixtamalized CM (NX diet) to provide 58 ppm (=14.3 nmol/g) hydrolyzed FB1 but no FB1, water-extracted CM (WE diet) to provide 8 ppm (=1.1 nmol/g) FB1, or CM to provide 71 ppm (=9.8 nmol/g) FB1 to the diet. A fourth group (SC diet) was fed a control diet. After 4 weeks, liver and kidney Sa and Sa/So of the NX diet group were significantly increased, but were less than those of the CM diet group. Severity of toxic effects in CM, NX, and WE diet fed rats were independent of FB1 or HFB1 diet levels (nmol/g), but were linearly correlated (p<0.05) with tissue Sa and Sa/So. Correlation was greatest (p<0.0001) for body weight gain and serum chemical indicators of hepatotoxicity. The findings indicate that HFB1, like FB1, inhibits ceramide synthetase in vivo and provides further evidence of the key role disrupted sphingolipid metabolism plays in the toxigenesis of fumonisin and fumonisin-like compounds.