31P NMR spectroscopy and polarographic combined study of erythrocytes treated with 5-fluorouracil: cardiotoxicity-related changes in ATP, 2,3-BPG, and O2 metabolism.
Antineoplastic drug 5-fluorouracil (5-FU) frequently shows cardiotoxic effects, the mechanism of which has not yet been elucidated. 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 to the phenomenon of 5-FU cardiotoxicity. We determined that 5-FU induced rapid increase in O(2) consumption, which led to drastic changes in the metabolism of phosphate compounds in erythrocytes. Decrease in pO(2) 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 could lead to a number of irreversible changes in erythrocyte structure and functioning, such as echinocytosis, increase in membrane fluidity, and non-functioning of membrane ion pumps. All these changes affect normal functioning of erythrocytes, leading to difficulties in oxygen transport and insufficient supply of oxygen to the heart, and pointing to the importance of studying the effects of antineoplastic drugs on intracellular metabolism of erythrocytes.
Spasojević
Ivan
I
Faculty of Physical Chemistry, University of Belgrade, Serbia and Montenegro.
Zakrzewska
Joanna
J
Bacić
Goran G
GG
D019794:2,3-Diphosphoglycerate / Q000097:blood*; D000255:Adenosine Triphosphate / Q000097:blood*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D010759:Phosphorus Isotopes; D013997:Time Factors
D000970:Antineoplastic Agents; D010759:Phosphorus Isotopes; D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate; D010100:Oxygen; D005472:Fluorouracil