Fumonisin Toxicity and Mechanism of Action: Overview and Current Perspectives

Abstract

Fumonisins are mycotoxins produced predominantly by Fusarium verticillioides and F. proliferatum. They contaminate maize and maize-based foods throughout the world. Fumonisin B₁ is the most common. It causes species-specific toxicities in laboratory and farm animals including liver and kidney cancer in rodents. Inhibition of ceramide synthase and disruption of sphingolipid metabolism is the non-genotoxic mechanism underlying its toxicological and carcinogenic effects. The extent to which fumonisin B₁ or other fumonisins impact human health remains poorly understood although epidemiological and experimental evidence implicate them as a risk factor for esophageal cancer and neural tube defects in populations consuming large amounts of contaminated maize-based foods. Selected toxicological investigations providing evidence for the above and serving as a basis for applied studies to better understand the extent of human exposure and potential risk are reviewed. The latter includes the use of kidney toxicity in rats as a bioassay showing that alkaline cooking (nixtamalization, the traditional method for making masa and tortillas) and extrusion effectively reduce the toxicity of fumonisin-contaminated maize and the development of robust exposure biomarkers for use in epidemiological studies. Future initiatives to better understand the relationship between fumonisins and human health should emphasize validation of biomarkers, such as urinary fumonisin B₁ concentration, as well as comparative studies to determine which animal models are most relevant to humans.