FUMONISINS - MECHANISMS OF ACTION AND TOXICOLOGY: IMPLICATIONS FOR IMMUNE RESPONSE

Authors: Norred, William; Riley, Ronald; Voss, Kenneth; Bacon, Charles

Submitted to: Proceedings of the Italian Society of Avian Pathologists
Publication Type: Proceedings
Publication Acceptance Date: 4/23/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: Fumonisins are toxins made by certain types of molds that can grow on crops. Fumonisins are commonly found on corn, and are the known cause of a fatal brain disease in horses, a fatal lung disease in pigs, and may cause performance problems, including depression of the immune system in other species, including poultry. They are also suspected of causing esophageal cancer in some parts of the world where people consume large quantities of corn. In this review paper, the toxicity caused by fumonisins is discussed, and the suspected mechanism of action by which fumonisins cause these diseases is described. Fumonisins appear to block the formation of a certain class of fats, or lipids, known as sphingolipids. These molecules normally occur in every cell, and perform many important functions that the cells depend on, such as when to grow and divide, and how to communicate with adjacent cells in the same tissue. Thus when fumonisin blocks the formation of these sphingolipids, cells behave erratically and die. Also, when the formation of sphingolipids is blocked by fumonisins, other lipids, which are components of sphingolipids which are normally present in very low levels, accumulate and are themselves toxic to cells. Understanding how fumonisins cause toxicity can help in treating, or more importantly, preventing, poisoning by these toxins.

Technical Abstract: Fumonisins are water soluble mycotoxins produced by several species of Fusarium fungi. The toxins are often found as contaminants of corn, apparently as a result of the endophytic relationship between corn and F. moniliforme, i.e. the fungus lives within the tissues of the corn plant, and may actually impart some beneficial qualities to the corn, such as enhanced disease or insect resistance. Fumonisins, however, are harmful to animals that consume contaminated corn, in particular horses and swine, and may be related to the high rates of esophageal cancer that occur in some parts of the world where corn is consumed as a staple. Fumonisins are specific inhibitors of the enzyme ceramide synthase (sphinganine and sphingosine N-acyltransferase), which is a key enzyme in the pathway leading to formation of sphingomyelin and complex sphingolipids. The disruption of this pathway has several important implications for cellular function, and there exists strong evidence suggesting that the toxicological properties of fumonisins are actually due to altered sphingolipid metabolism. In this paper, we will describe the nature of some observed toxicities of fumonisins, and discuss how these effects may be related to altered signaling pathways that are mediated through sphingoid bases and their metabolites, ceramides and more complex sphingolipids. The possible involvement of F. moniliforme and fumonisins in cases of impaired immune response in poultry flocks, and how altered sphingolipid metabolism could lead to immunomodulation will also be discussed.