Plasma membrane as a site of redox activation of daunomycin in intact human erythrocytes. Quantitative evaluation of the hydrogen peroxide produced by the membrane with respect to the cytosol.
The relative importance in human red blood cells of the plasma membrane as a site of redox activation of anthracyclines as compared to hemoglobin was evaluated by assaying the H2O2 produced upon exposure to daunomycin. The method of H2O2-dependent irreversible inhibition of catalase (EC 1.11.1.6) activity by 3-amino-1,2,4-triazole was applied to intact erythrocytes, as well as to isolated membranes with added purified catalase. The results obtained indicate a secondary role in daunomycin activation for the plasma membrane from a quantitative point of view, although membrane pathways can be more harmful than cytosolic pathways, especially towards extracellular targets, when the high efficiency of the cytosolic antioxidative defences and the external location of the membrane activation site are considered.
Marcocci
L
L
Department of Biochemical Sciences, University of Rome La Sapienza, Italy.
Pietrangeli
P
P
Mavelli
I
I
Rotilio
G
G
D000640:Amitrole / Q000494:pharmacology; D002374:Catalase / Q000037:antagonists & inhibitors; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D010084:Oxidation-Reduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000032:analysis
D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione; D000640:Amitrole; D003630:Daunorubicin