A comparison of furazolidone and doxorubicin enhanced free radical chemistry.
Furazolidone and doxorubicin induce dilative cardiomyopathies but are not structurally similar. In order to determine if these drugs might share a common mechanism of action, the free radical based chemistry of these drugs were compared. Furazolidone like doxorubicin stimulates lipid peroxidation in the presence of added iron. However, while furazolidone (50 microM) stimulated lipid peroxidation 2.4 fold, doxorubicin (50 microM) increased lipid peroxidation 10 fold in the presence of iron (50 microM). In contrast, furazolidone was more potent than doxorubicin at stimulating the oxidation of epinephrine and the reduction of cytochrome c when incubated with cardiac sarcosomes. These data demonstrate that while both drugs stimulate free radical chemistry, they differ in their propensity to stimulate iron-dependent (lipid peroxidation) versus iron-independent reactions. Thus differences in the expression of these drugs pathology may be due to differences in their redox chemistry.
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Department of Pharmacology, University of South Alabama, Mobile 36688.
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced; D003574:Cytochrome c Group / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D004837:Epinephrine / Q000378:metabolism; D005609:Free Radicals; D005664:Furazolidone / Q000494:pharmacology* / Q000633:toxicity; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D014422:Turkeys
D003574:Cytochrome c Group; D005609:Free Radicals; D005664:Furazolidone; D004317:Doxorubicin; D004837:Epinephrine