Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity.
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Gutierrez PL, Gee MV, Bachur NR
Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity.
Arch Biochem Biophys. 1983 May;223(1):68-75.
- PubMed ID
- 6305277 [ View in PubMed]
- Abstract
Adriamycin free radical anion concentrations have been correlated with production of 7-deoxyadriamycin aglycone in a reaction catalyzed by NADPH-cytochrome c reductase. The free radical species is detected by electron spin resonance (ESR) spectroscopy and quantified by double integrations. The 7-deoxyaglycone product is isolated by thin-layer chromatography (TLC) and quantified by fluorometry. As the concentration of adriamycin increases, a concomitant increase in aglycone and free radical levels occurs. These results as well as those with inhibitors Vitamin K3, Vitamin E, and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) point to an obligatory free radical intermediate in the metabolism of adriamycin. DMPO inhibits the reaction under aerobic conditions only, and shows no effect under anaerobiosis at the concentrations studied here. Vitamin E and aerobic DMPO act as free radical scavangers, while Vitamin K3 competes for the reducing power of NADPH in the NADPH-cytochrome c reductase system.
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- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Doxorubicin NADPH--cytochrome P450 reductase Protein Humans NoSubstrateDetails - Drug Reactions
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