|Merrill, jr, Alfred|
Submitted to: Natural Toxins
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/8/1995
Publication Date: N/A
Citation: Interpretive Summary: Fumonisins are toxins produced by molds which occur on corn and corn products consumed by humans and animals. These toxins can cause field outbreaks of animal diseases in pigs and horses and increase cancer risk in rats. For example, 38 horses died of a brain disease recently in Kentucky and Virginia after consuming corn or corn screening contaminated with these toxins. It is quite likely that in many other horses that ate the contaminated feeds the liver was damaged but the brain lesion did not develop. In all the diseases associated with consumption of fumonisins, it has been shown that there is a change in the way the tissues make certain very special fats. This change results in an accumulation of one type of fat called shinganine and a decrease in another type of fat called complex sphingolipids. It has been shown that the fat which accumulates can cause cells to die. Also, the change in the way these fats are accumulated can change the way tissues function. These changes in the fats have been related to the disease in animals and may excplain how the toxic fumonisins in corn and corn products cause the brain disease in horses, lung disease in pigs, and liver cancer in rats.
Technical Abstract: Fumonisins (FB) inhibit the biosynthesis of complex sphingolipids (e.g., ceramide, sphingomyelin, and gangliosides). In eucaryotic cells and microsomal preparations, FB inhibition of sphingolipid biosynthesis is a result of inhibition of the enzyme sphinganine (sphingosine) N- acyltransferase (ceramide synthase). Large increases in free sphinganine concentration in plant and animal cells are observed within a few hours after exposure to FBs and/or AAL-toxins. Some of the sphinganine is metabolized and some is released from cells. In animals free sphinganine appears in blood and urine. In cultured cells the accumulation of bioactive long-chain sphingoid bases and depletion of complex sphingolipids appear to account for the growth inhibition and cytotoxicity of FBs. Free sphingoid bases are toxic to most cells and this could account for some of the in vivo toxicity of the FBs. Recent studies have found that FBs impair the barrier function of endothelial cells and this might contribute to the neurotoxicity and pulmonary edema caused by FBs. Fumonisin B1 stimulates DNA synthesis in Swiss 3T3 cells, which may explain why FBs are tumor promoters and increase cancer risk in rats. Thus, FB induced changes in the sphingolipid composition of target tissues could directly or indirectly account for all facets of the Fusarium moniliforme associated diseases