A study about the effect of myeloperoxidase on doxorubicin used in leukemia treatment

Myeloperoxidase (MPO, EC 1.11.1.7) is an enzyme found in polymorphonuclear neutrophils and monocytes, and certain populations of tissue macrophages. Myeloperoxidase seems to play an important role in the defense system against invading microorganisms and certain tumor killing actions via myeloperoxidase-H2O2-Cl¯ reaction system. Myeloperoxidase also oxidizes various compounds such as phenols, anilines and their derivatives, and also ß-diketons which may lead to the formation of free radicals. In general, this explains the formation of toxic metabolites of certain drugs.Metabolite production by the effect of liver microsomes on some drugs used in cancer treatment and also the effect of Horseradish Peroxidase was studied previously. In this study, for the first time the effect of isolated and purified myeloperoxidase from human leukocytes, on Doxorubicin, which is used for leukemia treatment, was investigated. In addition, myeloperoxidase was obtained for the first time at adequate amounts and good activity to perform the reaction in laboratory conditions. The products formed in this reaction which was occured at physiological temperature and pH (37°C; pH 7.2-7.3) were evaluated by using UV-Vis. spectrophotometer, FT-IR and LC-MS spectrometer systems. In consequence, it was observed that the carbonyl group on Doxorubicin had disappeared, C-O-C ethereal bonds were broken and free radicals were formed.