TABLE 4

Secondary alcohol metabolite formation in isolated human heart cytosol: inhibitor studies

The incubations (0.25-ml final volume) contained human heart cytosol (0.15 mg of protein), 0.25 mM NADPH, and anthracyclines at three times their Km values (14.4, 224, and 750 μM, respectively). Secondary alcohol metabolites were measured at 4 hours in the absence or presence of inhibitors specific to aldehyde reductases (AL1576), carbonyl reductases (quercetin), and aldose reductases (EBPC). Inhibition curves were obtained with eight to 13 concentrations of each inhibitor (0.1 μM—1 mM range).


Anthracycline

AL1576

Quercetin IC50

EBPC
μM
Doxorubicinone 5 55 75
Doxorubicin 8 110 300
Epirubicin
7
60
100