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

According to the currently hypothesis, anthracyclines injure the heart by generating oxygen free radicals. Pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde isonicotinoyl hydrazone (SIH) - new iron chelators to protect against peroxidation.

Activities of cytosolic reductases and P450 isoenzymes involved in metabolism of daunorubicin, doxorubicin. Various chelator, daunorubicin and doxorubicin concentrations were used for in vitro studies on isolated hepatocytes.

The results show that PIH and SIH have no effect on the activities of the enzymes studied in vitro. Anthracyclines significantly reduce cytochrome P450 activity, but the addition of SIH and PIH chelators (50 mM) reverses the reduction and restores the activity to 70-90 % of the activity of relevant controls.