Subchronic toxic effects of Fusarium moniliforme and fumonisin B1 in rats and mice

Fumonisins are mycotoxins produced by the fungi Fusarium moniliforme, F. proliferatum, and other Fusarium species. Fumonisin B1, the most commonly found fumonisin, causes the fatal diseases equine leukoencephalomalacia and porcine pulmonary edema. Fumonisins are suspected human carcinogens because of the extraordinarily high incidences of esophageal cancer coincidentally found in areas of southern Africa and China where F. moniliforme-contaminated corn is consumed as a dietary staple. The subchronic (up to 90 days) effects of F. moniliforme-contaminated corn, corn cultures of this fungus, and purified fumonisin B1 (FB1) in rats and mice were systematically studied to determine target organs, characterize organ-specified lesions, and obtain dose-response data. The liver is a target organ in both species. Serum chemical findings indicative of hepatocellular injury and morphological findings, including apoptosis, appeared qualitatively similar in both species. The kidney is also a target organ in rats, but not mice. Lesions which include apoptosis and cellular degeneration are predominately found in the outer medella. Results of several investigations showed that the kidney was consistently affected at lower doses than the liver. The "no-observed-effect" level for nephropathy in rats was also consistently lower in males than females, suggesting a sex-related difference in nephrotoxic response to fumonisins. Other findings suggest that toxigenesis may be mediated by disruption of de novo sphingolipid biosynthesis. Hepatic and renal sphingolipid profiles, specifically sphinganine concentration and sphinganine-to-sphingosine ratio, were altered in rats fed FB1 at levels that did not cause serum chemical, organ weight, or histopathological evidence of toxicity.