Fusarium moniliforme contaminated corn has been associated with several human and animal diseases, including luekoencephalomalacia (LEM) in horses, pulmonary edema in swine, and hepatoxi-city in horses, swine, and rats. Both culture material from F. moniliforme-inoculated corn and pure FB1 are capable of producing similar effects in animals. Neurotoxic signs and symptoms, including loss of feed consumption, lameness, ataxia, oral and facial paralysis, and recumbency, begin within days after initial consumption of moldy corn or by direct administration of FB1 and may be rapidly followed by seizures and morbidity. Focal malacia and liquefaction of cerebral white matter with peripheral hemorrhage is the pathog-nomonic finding.
Studies have provided possible insights into the mechanisms of toxicity. The fumonisins bear considerable structural similarity to the long-chain (sphingoid) base backbones of sphingolipids. It was demonstrated that incubation of rat hepatocytes with fumonisins inhibited sphingosine biosynthesis. FB1 increased the amount of the biosynthetic intermediate sphinganine, which suggests that fumonisins inhibit the conversion of sphinganine to N-acyl-sphinganines. It was subsequently shown, using mouse cerebellar neurons in culture, that FB1 inhibited ceramide synthase in mouse brain microsomes with a competitive-like kinetic behavior with respect to both sphinganine and stearoyl-CoA. Thus, disruption of the de novo pathway of sphingolipid biosynthesis may be a critical event in the diseases that have been associated with consumption of fumonisins.
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