Fumonisins are produced by species of Fusarium. In the U.S., the ingestion of moldy corn was first associated with adverse health affects in farm animals.
Examples are: Horses (sloughing of of hooves and liquefaction of the cerebral hemisphere white matter, also known as equine leukoencephalomalacia) and pigs (porcine pulmonary edema).
Laboratory treatment of a variety of animals (rats, mice, sheep and baboons) caused hepatosis, nephrosis, congestive heart failure and cholangiocarcinoma (Nelson et al, 1993; Dragan et al, 2001; Masas, 2001; Gelderblom et al, 2002; Riley et al, 2001; Lemmer et al, 2004 ).
In humans, Fumonisins have been associated with esophageal cancer from ingested contaminated corn (Marsas, 2001). More recently, they have been implicated in birth defects (neural tube) in humans and animals.
In addition, Fumonisins are liver and kidney toxins and carcinogenic in rodents (Dragan et al, 2001; Masas, 2001; Gelderblom et al, 2002; Riley et al, 2001).
The chemical mechanism of the toxic action of fumonisin B1 will be briefly reviewed below.
Fumonisin B1 (FB 1) inhibits the production of Ceramide by inhibiting the enzyme ceramide synthase. This disrupts the sphingolipid pathway leading to intracellular and extracellular accumulation of toxic by-products of the pathway. The sphingolipids are cell membrane structures, providing integrity of the membranes.
FB 1 inhibits the enzyme ceramide synthase preventing the formation of ceramide. This disrupts the synthesis of critical sphingolipids downstream of ceramide, e.g., Sphingomyelin and glycosphingolipids.
In the process, precursors of ceramide increase in concentration (e.g., sphinganine, sphingosine1-phosphate, as well as deoxysphinganine and other deoxyspingoid bases) (Riley et al, 2001; He et al, 2006 Zitomer et al, 2009).
The accumulated metabolites are highly toxic, causing cytotoxicity and cell death (apoptosis) (Yoo et al, 1996; Desai et al, 2002).
In addition, reactive oxygen species (ROS) have been shown to be active in apoptosis and damage to DNA (Stockman-Juvala et al, 2004; Domijan et al, 2007).
Finally, the disruption of sphingolipid metabolism has been associated with neural tube defects (NTDs) in animal models in vivo and in vivo as well was in humans living along the Texas-Mexico border. The NTDs are discussed in the section on neurotoxicity and mycotoxins mentioned above (Marasas et al, 2003; Gelineau-van Waes et al, 2005, 2009; Missmer et al, 2006).
In addition, intracerebroventricular administration of FB 1to mice caused neurodegeneration, disruption of sphingolipid metabolism, stimulation of astrocytes and release of pro-inflammatory cytokines: TNF-α, IL1 beta, IL6 and IF- gamma (Osuchowski et al, 2005).