Current Issues in Research on Fumonisins, Mycotoxins Which May Cause Nephropathy

Abstract

The fumonsins are a series of mycotoxins produced by the ubiquitous corn (maize) contaminant, Fusarium moniliforme, and several other Fusarium species. Fumonisin B₁ (FB₁), the major component of the fumonisins, causes leukoencephalomalacia in horses, pulmonary edema in swine and hepatocellular carcinoma, cirrhosis and chronic interstitial nephritis in rats. Also, consumption of corn-derived food products contaminated with F. moniliforme has been correlated with increased risk of human esophageal cancer in epidemiological stumes in South Africa and China. In the kidneys of rodents, dietary exposure to FB₁ produces a dose-related non-inflammatory nephrosis with regeneration at low doses. Individual cells die by induction of apoptosis. The fumonisins have chemcal structures analogous to sphingosine, a putative intracellular regulatory molecule, and a component of sphingolipids. The alkylamine structure of FB₁ makes possible sensitive high performance liquid chromatography (HPLC) assays based on pre-column derivatization of the amino group with fluorogenic reagents. These assays have been used to demonstrate that FB₁ contaminates most corn and corn-derived processed food products intended for human consumption. Conventional thermal food processing techniques reduce FB₁ levels, but do not completely eliminate it. Structure-activity relationship studies carried out in our laboratories on natural and synthetic fumonisins indicate that extensive alterations in structure are possible without loss of biological activity. This observation raises the concern that the FB₁ eliminated during food processing may actually be converted to other biologically active forms. The full extent of the threat to food safety posed by fumonisins will not be known until it is determjned what substances the toxin is converted to during food processing, the bioavailability of those substances, the extent they retain biological activity and the additivity of their toxic effects with other nephrotoxic mycotoxins such as ochratoxins A and B.