Generation of Superoxide Radicals by Heart Mitochondria and the Effects of Dinitrosyl Iron Complexes and Ferritin

Mitochondrial dysfunction, which may be due to excessive generation of toxic forms of oxygen and nitrogen in oxidative stress, is one of the risk factors for a wide range of pathologies. Reactive oxygen species (ROS) and reactive nitrogen species are continuously generated in living organisms by enzymes and redox processes, such as the iron-catalyzed Fenton and Haber–Weiss reactions. Literature data demonstrate the relationships between ferritin metabolism, ROS, nitric oxide, and dinitrosyl iron complexes (DNICs) and indicate that DNICs play an important role in antioxidant defense mechanisms. Pro-oxidant and antioxidant properties of DNICs and ferritin were studied in two superoxide-generating systems, heart mitochondria and a xanthine–xanthine oxidase system, by EPR spin trapping, spectrophotometry, and polarography. DNICs with glutathione ligands were shown to intercept reactive free radicals in the systems, which simulate oxidative stress in cardiac muscle cells. Ferritin stimulated DNIC destruction in the same conditions. These findings suggest antioxidant and antiradical effects for DNICs and a pro-oxidant effect for ferritin.