Furazolidone-enhanced production of free radicals by avian cardiac and hepatic microsomal membranes.
Furazolidone produces a dilative cardiomyopathy and hepatitis in turkeys exposed to this drug in their diets. The ability of furazolidone to enhance free radical reactions when incubated with turkey cardiac or hepatic membranes was determined to evaluate if free radical reactions might contribute to the pathology. Furazolidone (0.135 mM) incubated with NADPH and hepatic microsomes increased oxygen consumption 350% over control incubations. Superoxide dismutase and catalase attenuated the furazolidone-mediated stimulation of oxygen consumption, indicating that the drug promoted the formation of superoxide and hydrogen peroxide. Lipid peroxidation was also stimulated by furazolidone incubated with microsomes, NADPH, and ferric chloride. At concentrations as low as 0.017 mM, lipid peroxidation was more than doubled by furazolidone. Incubation of cardiac sarcosomes with NADPH and furazolidone (0.135 mM) increased oxygen consumption 72% the rate of cytochrome c reduction 72%, and epinephrine oxidation 238% over control. Epinephrine oxidation was enhanced by concentrations of furazolidone as low as 0.017 mM (69% increase over control). This effect of furazolidone was blocked by superoxide dismutase or incubation in an argon atmosphere. These data establish the potential for furazolidone to enhance free radical reactions in cardiac, as well as hepatic tissue. Free radical reactions are therefore potential determinants of furazolidone-mediated hepatic and cardiac toxicities.
Stroo
W E
WE
Department of Pharmacology, University of South Alabama College of Medicine, Mobile 36608.
Schaffer
S W
SW
D000818:Animals; D004837:Epinephrine / Q000378:metabolism; D005609:Free Radicals; D005664:Furazolidone / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects; D008054:Lipid Peroxides / Q000096:biosynthesis; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014422:Turkeys
D005609:Free Radicals; D008054:Lipid Peroxides; D013481:Superoxides; D005664:Furazolidone; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D009245:NADH Dehydrogenase; D004837:Epinephrine