Fusarium mycotoxin toxicosis has been implicated as an etiological factor for Keshan disease, an endemic cardiomyopathy prevailing in specific regions of China. Butenolide (4-acetamido-4-hydroxy-2-butenoic acid γ-lactone) is one of the Fusarium mycotoxins frequently detected from the foodstuffs of endemic areas and has been shown to possess the potential to induce cardiotoxicity, implying this mycotoxin might play a role in the occurrence of Keshan disease. The present study was undertaken to further investigate the myocardial toxicity of butenolide from a viewpoint of oxidative damage. A single in ovo injection of butenolide to chick embryos, an excellent in vitro toxicology model resulted in significant oxidative injuries to the myocardium, manifested by a dose-dependent depletion of sulfhydryl groups, reduction of glutathione peroxidase (GPx) activity, and increase of thiobarbituric acid reactive substances production, a hallmark of lipid peroxidation. In contrast, co-injections of butenolide to chick embryos with sodium selenite or vitamin C, two potent antioxidants, markedly abated these oxidative injuries.
In conclusion, the present study clearly indicated that butenolide could induce significant myocardial oxidative injuries. The current findings reinforce the hypothesis that toxicosis by Fusarium mycotoxins may be one of the etiological factors for Keshan disease, and oxidative damage is involved in the pathogenesis of myocardial toxicity.