PMID: 9181603May 1, 1997Paper

Carbonyl reduction of daunorubicin in rabbit liver and heart

Pharmacology & Toxicology
D Pröpper, E Maser

Abstract

A major problem of anthracycline anticancer treatment are the cardiotoxic side effects associated with drug therapy. Increased attention has recently been focused on the 13-hydroxy anthracycline metabolites which are formed by carbonyl reduction of the parent drug as contributing to cardiotoxicity. By using daunorubicin as a reference molecule, our study was designed to quantitatively evaluate and compare the extent of anthracycline carbonyl reduction of liver and heart at the physiological important pH 7.4, and to identify the enzyme(s) involved under these conditions. The present kinetic data indicate that only one single enzyme system is active in cytosol of both tissues. According to its specific inhibition by quercitrin and the failure of a barbiturate to affect activity the enzyme responsible for daunorubicin carbonyl reduction in these fractions is carbonyl reductase (EC 1.1.1.184). Since the KM values differ significantly from each other, it is suggested that liver and heart express different isoforms of this enzyme. We failed to detect any specific daunorubicin carbonyl reductase activity in both microsomal fractions. Intrinsic clearance values revealed that liver has obviously 350-times the capacity of total 13-hydrox...Continue Reading

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Citations

Mar 1, 2000·Drug Metabolism and Drug Interactions·L SkálováE Kvasnicková
Dec 13, 2005·Journal of Enzyme Inhibition and Medicinal Chemistry·Helena Kaiserová, Eva Kvasnicková
Oct 25, 2008·Drug Metabolism Reviews·Oleg A BarskiAruni Bhatnagar
Jan 17, 2016·Toxicology and Applied Pharmacology·Jan HintzpeterEdmund Maser
Aug 5, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Weixue HuangLong Yu
Jun 23, 2000·The Journal of Pharmacy and Pharmacology·B SzotákováE Kvasniècková

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