Effects of 5-fluorouracil on erythrocytes in relation to its cardiotoxicity: membrane structure and functioning.
In the present study, we showed that the antineoplastic drug 5-fluorouracil (5-FU) induces in vitro exposure-time/dose-dependent changes on the level of an erythrocyte's morphology, ionic balance, and membrane fluidity. These changes are partially or fully irreversible, and we suggest that they are provoked by an irreversible depletion of ATP. Because of these changes that could also occur in vivo during 5-FU infusion, a certain amount of erythrocytes with echinocytic shape and diminished ability to deliver oxygen is present in blood for longer periods of time. This renders oxygen transport and delivery more difficult, leaving the heart with an insufficient supply of oxygen, thus leading to cardiotoxicity.
Spasojević
Ivan
I
Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia and Montenegro.
Maksimović
Vuk
V
Zakrzewska
Joanna
J
Bacić
Goran
G
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004734:Energy Metabolism / Q000502:physiology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000648:ultrastructure; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D005472:Fluorouracil / Q000494:pharmacology* / Q000633:toxicity*; D006331:Heart Diseases / Q000139:chemically induced*; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008560:Membrane Fluidity; D010101:Oxygen Consumption / Q000502:physiology; D011188:Potassium / Q000097:blood; D013113:Spin Labels
D000964:Antimetabolites, Antineoplastic; D013113:Spin Labels; D011188:Potassium; D005472:Fluorouracil