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Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia
Institute for Multidisciplinary Research, University of Belgrade, Kneza Višeslava 1, Belgrade, 11000, Serbia
National Cancer Research Institute, Pasterova 14, Belgrade, 11000, Serbia
Insitute of General and Physical Chemistry, Studentski trg 12-16, Belgrade, 11000, Serbia
Faculty for Physical Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade, 11000, Serbia
* Author to whom correspondence should be addressed.
Received: 15 October 2008; in revised form: 21 December 2008 / Accepted: 24 December 2008 / Published: 28 December 2008
Abstract: cisplatin have similar effects on the erythrocyte membrane, thus eliminating those changes as a potential source of cardiotoxicity. On the contrary, 31P-NMR and polarography showed that the effects of these cytostatics on the intracellular milieu differ significantly. 5-FU provoked a pronounced decrease of the O2 level in blood and affected the metabolism of phosphate compounds, while cisplatin had no such effects. When combined these two drugs showed synergistic effects, which matches the higher frequency of cardiotoxicity of the combination relative to the sole application of 5-FU. Preliminary results acquired on blood of patients receiving cisplatin/5-FU therapy verified observations obtained ex vivo. These results open a possibility of applying NMR in preclinical trials of new drugs in order to predict their ischemic potential.
Keywords: 5-Fluorouracil; Cisplatin; Ischemia; Erythrocytes; 31P NMR spectroscopy
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Spasojević, I.; Jelić, S.; Zakrzewska, J.; Bačić, G. Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia. Molecules 2009, 14, 53-67.
Spasojević I, Jelić S, Zakrzewska J, Bačić G. Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia. Molecules. 2009; 14(1):53-67.
Spasojević, Ivan; Jelić, Svetislav; Zakrzewska, Joanna; Bačić, Goran. 2009. "Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia." Molecules 14, no. 1: 53-67.