Lipid peroxidation of rat erythrocyte membrane induced by adriamycin-Fe3+.
Adriamycin-Fe3+ caused lipid peroxidation of erythrocyte membrane in relation to its concentration. Adriamycin-Fe3+ had a high affinity for membrane and the adriamycin-Fe(3+)-binding membranes membranes was also found to cause lipid peroxidation. Under aerobic conditions, adriamycin-Fe3+ caused a reduction of cytochrome c and ferrous iron formed spontaneously. Superoxide dismutase (EC 1.15.1.1) (SOD) strongly inhibited the reduction of cytochrome c; however, the enzyme promoted formation of ferrous iron independent of enzymatic action. These results suggest that cytochrome c was reduced by superoxide radical (O2-) or an adriamycin-iron-O2 complex such as adriamycin-Fe(3+)-O2-, but not by adriamycin-Fe2+. The ferrous iron chelator bathophenanthroline sulfonate (BPS) completely inhibited oxygen consumption caused by adriamycin-Fe3+, indicating that ferrous iron is absolutely required for the lipid peroxidation. SOD and hydroxyl radical scavengers did not inhibit the lipid peroxidation, indicating that O2- and hydroxyl radical were not involved in membrane peroxidation. The peroxidation reaction was dramatically inhibited by Tris buffer (2-amino-2-hydroxymethyl-1,3-propanediol). However, hydroxyl radical generation and lipid peroxidation in Tris buffer were not related obviously, indicating that Tris did not act as a hydroxyl radical scavenger. The initial rate of TBARS (thiobarbituric acid reactive substances) formation induced by a mixture of adriamycin-Fe3+ and adriamycin-Fe2+ was much faster than that induced by adriamycin-Fe2+ or adriamycin-Fe3+ alone. These results made it became possible to speculate that the lipid peroxidation might be initiated by an adriamycin-Fe(3+)-oxygen-adriamycin-Fe2+ complex.
Miura
T
T
Department of Biochemistry, Hokkaido Institute of Pharmaceutical Sciences Katsuraokacho, Otaru, Japan.
Muraoka
S
S
Ogiso
T
T
D000818:Animals; D003574:Cytochrome c Group / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; C041415:doxorubicin-iron complex; D004317:Doxorubicin; D007501:Iron; D010100:Oxygen