bongkrekic-acid and 2-2-5-7-8-pentamethyl-1-hydroxychroman

The role of NAD(P)H-dependent oxidoreductases of the outer mitochondrial membrane (OMM) in the activation of lipophilic cationic dyes is poorly understood. In the present study we compared the rates of production of reactive oxygen species (ROS) and mitochondriotoxic effects of the redox-cycling lipophilic cationic dye lucigenin upon its activation by the respiratory chain and NAD(P)H-dependent oxidoreductases of the OMM. We found that, only in the presence of external NADH and NADPH, which are unable to penetrate the inner membrane, lucigenin stimulated a massive superoxide production and a fast permeabilization of mitochondrial membranes. The permeabilization was biphasic. The first, cyclosporin A-insensitive and Ca(2+)-independent phase was characterized by increased permeability of the inner mitochondrial membrane to solutes with molecular masses of

Topics: Acridines; Animals; Antifungal Agents; Bongkrekic Acid; Catalase; Cations; Chromans; Cyanides; Dose-Response Relationship, Drug; Egtazic Acid; Electron Transport; Free Radical Scavengers; Hydrophobic and Hydrophilic Interactions; Luminescent Agents; Male; Membrane Potential, Mitochondrial; Mitochondrial Membrane Transport Proteins; Mitochondrial Membranes; Mitochondrial Permeability Transition Pore; Mitochondrial Swelling; NADH, NADPH Oxidoreductases; Oxidation-Reduction; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase