Generation of furazolidone radical anion and its inhibition by glutathione

Furazolidone is a nitrofuran drug which causes dilated cardiomyopathy in turkeys and serves as an important model of human dilated cardiomyopathy. Although extensively investigated, the chemical mechanism by which furazolidone produces injury remains unknown. In this work we used electron paramagnetic resonance (EPR) spectroscopy to show that furazolidone was reduced to its corresponding nitro anion radical by ascorbate and hypoxanthine. Glutathione prevented the generation of this anion radical. These results document directly, with EPR spectroscopy, the presence of furazolidone anion radical during biochemical reduction and suggest a protective role of glutathione in furazolidone-induced injury. These data enhance our understanding of furazolidone metabolism and may be useful in defining its role in furazolidone-induced dilated cardiomyopathy.