Destruction of phospholipids and respiratory-chain activity in pig-heart submitochondrial particles induced by an adriamycin-iron complex.
Ferric ion complexes of the antibiotic and antitumor agent adriamycin support peroxidation of phospholipids in pig heart submitochondrial particles as judged by disappearance of polyunsaturated fatty acids, loss in extractable phospholipid, adriamycin-Fe3+-dependent oxygen consumption and formation of material with ultraviolet absorption. Peroxidation was stimulated to an extent of about 100% at low rates of NADH oxidation in the submitochondrial particles, whereas oxidation rates higher than 50 nmol NADH oxidized x min-1 x mg protein-1 appeared to protect the membrane lipids. NADH oxidase, NADH-cytochrome c reductase as well as cytochrome c oxidase activities in the submitochondrial particles were progressively inactivated during incubation with adriamycin in the presence of Fe3+ ions, whereas NADH-ferricyanide reductase activity remained fully stable.
D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism*; D013552:Swine
D008054:Lipid Peroxides; D009097:Multienzyme Complexes; D010743:Phospholipids; D004317:Doxorubicin; D007501:Iron; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases