The Effect of New Lipophilic Chelators on the Activities of Cytosolic Reductases and P450 Cytochromes Involved in the Metabolism of Anthracycline Antibiotics: Studies in Vitro
Abstract
Activities of carbonyl reductase CR (1.1.1.184), dihydrodiol dehydrogenase DD2 (1.3.1.20), aldehyde reductase ALR1 (1.1.1.2) and P450 isoenzymes (CYP1A1, CYP1A2, CYP2B, CYP3A) involved in the metabolism of daunorubicin, doxorubicin and other drugs or xenobiotics were studied. A significant decrease of activity was observed for all enzymes only at PIH and SIH concentrations higher than those presumed to be used for therapy.
The results show that PIH and SIH have no effect on the activities of the enzymes studied in vitro and allow us to believe that they will not interfere with the metabolism of co-administered drugs and other xenobiotics. Daunorubicin (Da) and doxorubicin (Dx) significantly reduce cytochrome P450 activity, but the addition of SIH and PIH chelators (50 ?M) reverses the reduction and restores the activity to 70-90 % of the activity of relevant controls.