5-Fluorouracil effects on erythrocytes in relation to its cardiotoxicity: I. 31P NMR spectroscopy and polarographic studies of ATP, 2,3-BPG and O2 metabolism

Ivan Spasojević (1,2), Joanna Zakrzewska (3) Goran Bačić (1)

(1) Faculty of Physical Chemistry, (2) Center for Multidisciplinary Studies, University of Belgrade (3) HP Institute of General and Physical Chemistry, Belgrade

Antineoplastic drug 5-FU shows unexplained cardiotoxic effects. It was reported that 5-FU cardiotoxicity is an ischemic manifestation, which could not be related with vascular wall changes, but rather with changes induced on erythrocytes. 5-FU is known to pass the erythrocyte membrane and to induce echinocytosis and changes in membrane components of the oxygen delivery system. The objective of the present study was to explore effects of 5-FU on metabolism of ATP, 2,3-BPG and oxygen in erythrocytes and to relate these with 5-FU cardiotoxicity. We determined that 5-FU induced rapid increase in O2 consumption, which led to drastic changes in the metabolism of phosphate compounds in erythrocytes. Decrease in pO2 provoked increase in production of 2,3-BPG and subsequent deoxygenation of oxyHb to deoxyHb. However, the most important effect of 5-FU on erythrocytes is severe decrease in the level of ATP. This leads to a number of irreversible changes in erythrocyte structure (see paper II) and functioning, affecting oxygen unloading properties of erythrocytes which in turn may lead to ischemia.

Email: ggbacic@ffh.bg.ac.yu

Address: Faculty of Physical Chemistry, University of Belgrade, Belgrade Studentski trg 12-16