NADH oxidation in submitochondrial particles protects respiratory chain activity against damage by adriamycin-Fe3+.
Oxidative decomposition of polyunsaturated fatty acid moieties of membrane lipid in pig heart submitochondrial particles, as initiated by ferric ion complexes of the antineoplastic drug adriamycin and concomitant inactivation of oxidase activities, is counteracted by EDTA, low oxygen pressure, a phenolic antioxidant and NADH oxidation through the respiratory chain but not by scavengers of reactive oxygen species. Protection by NADH is strengthened by removal of cytochrome c from the submitochondrial particles and by antimycin A but abolished by rotenone. Inhibition of cytochrome c oxidase activity by the adriamycin-Fe3+ complex is reversible and activity is recovered upon cholate solubilization of the particles. ADP inhibits binding of the complex to the submitochondrial particles and protects both cytochrome c oxidase activity and membrane lipid. The results are discussed in relation to the possible role of mitochondrial function in protection against free-radical-mediated effects of adriamycin.
D000818:Animals; D003580:Cytochromes / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D004579:Electron Transport / Q000187:drug effects*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity*; D008054:Lipid Peroxides / Q000096:biosynthesis; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
D003580:Cytochromes; D005290:Ferric Compounds; D008054:Lipid Peroxides; D009097:Multienzyme Complexes; D004317:Doxorubicin; D007501:Iron; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV