Fumonisins as Potential Causes of Kidney Disease

Abstract

The fumonisins are a series of sphingosine-analog mycotoxins produced by the ubiquitous corn (maize) contaminant Fusarium moniliforme. The major component, fumonisin B₁ (FB₁), has been shown to cause leukoencephalomalacia in horses, pulmonary edema in swine and hepatocellular carcinoma, cirrhosis and chronic interstitial nephritis in rats. Consumption of corn-derived food products contaminated with F. moniliforme has been correlated with increased risk of human esophageal cancer in several epidemiological studies. High performance liquid chromatography (HPLC) assays using pre-column derivatization with fluorogenic reagents have been developed for FB₁, and used to demonstrate that FB₁ contaminates most corn and corn-derived processed food products intended for human consumption. Most types of food processing reduce FB₁ levels, but they do not completely eliminate it. A sensitive bioassay for mycotoxins, including FB₁ and ochratoxins, has been developed using cytotoxic effects on cultured mammalian cell lines of kidney origin. Cell lines which appear to have retained differentiated characteristics of tubular epithelial cells exhibit an unusual sensitivity to FB₁ (about 10-fold increased sensitivity), which was not observed with other kidney-derived cell lines, which appeared to be fibroblasts. Ochratoxins A and B exhibited similar cytotoxic effects with all kidney-derived cell lines examined. Selective toxicity for tubular epithelial cells is consistent with reported FB₁ nephrotoxicity in rats. These observations raise the concern that co-administration of fumonisins may alter the nephrotoxicity of ochratoxins and other nephrotoxic mycotoxins. This is of particular concern in Egypt, where FB₁ contamination levels as high as 3 μg/g have been reported in corn, and daily consumption of >500 g of cereals is typical.

Structure-activity relationship studies carried out on natural and synthetic fumonisins with this bioassay system indicate that extensive alterations in structure are possible without loss of biological activity. This observation raises the concern that FB₁ being eliminated during food processing may actually be getting converted to other biologically active forms. The full extent of the threat to food safety posed by the fumonisins will not be known until it is determined what substances the toxin is converted to during food processing, and whether they retain biological activity. Similarly, it is doubtful if any rational approach to the removal of fumonisin contamination from foods can succeed without knowing which degradation processes lead to biologically active products.