Key result
5-fluorouracil treatment of erythrocytes induced a rapid increase in O2 consumption and a severe decrease in ATP levels, potentially contributing to its cardiotoxic effects.
Why the study?
Does 5-fluorouracil alter the metabolism of ATP, 2,3-BPG, and oxygen in erythrocytes?
Does 5-fluorouracil alter the metabolism of ATP, 2,3-BPG, and oxygen in erythrocytes?
5-fluorouracil causes severe ATP depletion and altered oxygen metabolism in erythrocytes, suggesting a novel mechanism for its cardiotoxic effects through impaired oxygen delivery.
5-FU erythrocyte ATP depletion may impair cardiac oxygen delivery; hypothesis-generating for cardiotoxicity and requires human validation.
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.
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Spasojević et al. (2005) studied 5-Fluorouracil cardiotoxicity. 5-Fluorouracil (5-FU) was evaluated on Metabolism of ATP, 2,3-BPG, and oxygen in erythrocytes. 5-fluorouracil treatment of erythrocytes induced a rapid increase in O2 consumption and a severe decrease in ATP levels, potentially contributing to its cardiotoxic effects.
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