TY  - JOUR
AU  - Spasojević, Ivan
AU  - Jelic, Svetislav
AU  - Zakrzewska, Joanna
AU  - Bačić, Goran
PY  - 2009
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/309
AB  - Various mechanisms have been proposed to account for chemotherapy related ischemia, but none of them can explain the available clinical data. In order to explore the possibility that the decreased ability of erythrocytes to deliver oxygen to the heart could be responsible for cardiotoxicity, we have performed an ex vivo and in vivo study of the effects of cisplatin/5-FU on erythrocytes, using a variety of biophysical techniques. Combining EPR and microscopy it was concluded that both cardiotoxic 5-FU and non-cardiotoxic cisplatin have similar effects on the erythrocyte membrane, thus eliminating those changes as a potential source of cardiotoxicity. On the contrary, P-31-NMR and polarography showed that the effects of these cytostatics on the intracellular milieu differ significantly. 5-FU provoked a pronounced decrease of the O-2 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.
PB  - MDPI, Basel
T2  - Molecules
T1  - Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia
EP  - 67
IS  - 1
SP  - 53
VL  - 14
DO  - 10.3390/molecules14010053
ER  - 

@article{
author = "Spasojević, Ivan and Jelic, Svetislav and Zakrzewska, Joanna and Bačić, Goran",
year = "2009",
abstract = "Various mechanisms have been proposed to account for chemotherapy related ischemia, but none of them can explain the available clinical data. In order to explore the possibility that the decreased ability of erythrocytes to deliver oxygen to the heart could be responsible for cardiotoxicity, we have performed an ex vivo and in vivo study of the effects of cisplatin/5-FU on erythrocytes, using a variety of biophysical techniques. Combining EPR and microscopy it was concluded that both cardiotoxic 5-FU and non-cardiotoxic cisplatin have similar effects on the erythrocyte membrane, thus eliminating those changes as a potential source of cardiotoxicity. On the contrary, P-31-NMR and polarography showed that the effects of these cytostatics on the intracellular milieu differ significantly. 5-FU provoked a pronounced decrease of the O-2 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.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia",
pages = "67-53",
number = "1",
volume = "14",
doi = "10.3390/molecules14010053"
}

Spasojević, I., Jelic, S., Zakrzewska, J.,& Bačić, G.. (2009). Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia. in Molecules
MDPI, Basel., 14(1), 53-67.
https://doi.org/10.3390/molecules14010053

Spasojević I, Jelic S, Zakrzewska J, Bačić G. Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia. in Molecules. 2009;14(1):53-67.
doi:10.3390/molecules14010053 .

Spasojević, Ivan, Jelic, Svetislav, Zakrzewska, Joanna, Bačić, Goran, "Decreased Oxygen Transfer Capacity of Erythrocytes as a Cause of 5-Fluorouracil Related Ischemia" in Molecules, 14, no. 1 (2009):53-67,
https://doi.org/10.3390/molecules14010053 . .