Cardiovascular toxicity induced by fumonisin in pigs and horses.

摘要

Fumonisins are a group of mycotoxins produced primarily by the fungus Fusarium verticillioides (formerly F. moniliforme), one of the most prevalent fungi associated with corn intended for human and animal consumption. Since their isolation in the 1988, these toxic fungal metabolites have been shown to induce acute lethal pulmonary edema in pigs and leukoencephalomalacia in horses. The main purpose of these studies was to examine the cardiovascular effects of fumonisin toxicity in pigs and horses. The overall goal of the research was to expand our knowledge of fumonisin toxicity, and determine the pathophysiological mechanism of fumonisin-induced porcine pulmonary edema and equine leukoencephalomalacia. In a series of four experiments involving oral ingestion of fumonisin-containing culture material and intravenous administration of fumonisin B₁, we demonstrated that fumonisin B₁ decreases cardiac contractility, heart rate, cardiac output, and mean arterial pressure, and increases mean pulmonary artery pressure and pulmonary artery wedge pressure in pigs. The onset of hemodynamic changes was temporally associated with increases in plasma sphinganine and sphingosine concentrations, compounds which are known to inhibit cardiac L-type calcium channels. We concluded that fumonisin-induced pulmonary edema in swine was caused by acute left-sided heart failure, which was most likely induced by sphingosine-mediated L-type calcium channel blockade. In a subsequent study in horses, we demonstrated that the intravenous administration of fumonisin B₁ decreased heart rate, cardiac output and cardiac contractility, and induced clinical signs of neurologic disease. These findings suggest that fumonisin-induced cardiovascular depression may contribute to the pathophysiology of equine leukoencephalomalacia.