5-Fluorouracil effects on erythrocytes in relation to its cardiotoxicity: II. Membrane structure and functioning

Ivan Spasojević (1,2), Vuk Maksimović (2) Goran Bačić (1)

(1) Faculty of Physical Chemistry, (2) Center for Multidisciplinary Studies, University of Belgrade

5-Fluorouracil (5-FU) is known to provoke unexplained cardiotoxic effects. This in vitro study is an attempt to relate reported cardiotoxicity with 5-FU induced changes on erythrocytes membrane. We determined using HPLC assay method that 5-FU rapidly passes the erythrocytes membrane. 5-FU provokes exposure-time/dose dependent transformation of erythrocytes into the echinocytic shape which is irreversible after prolonged incubation times. Also 5-FU induces increased efflux of potassium, which is a good evidence of the disarrangements of the membrane structure. EPR study of membrane fluidity using fatty acid spin-probe 7-DS showed that 5-FU increases fluidity of erythrocyte membrane. Changes were irreversible at high concentrations of 5-FU. In addition we have shown that 5-FU affects band 3 macrocomplex on erythrocytes membrane which is involved in CO2/O2 gas exchange. The cause of all these changes is most likely the decrease in ATP level induced by 5-FU (see paper I). Consequently, a certain amount of erythrocytes with echinocytic shape and diminished ability for oxygen delivery could be present in the blood of 5-FU treated patients for longer periods of time. This could render oxygen transport and/or delivery more difficult, leaving heart with insufficient supply of oxygen so ischemic damage occurs.

Email: ggbacic@ffh.bg.ac.yu

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