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Volume 21, Issue 2, Pages 121-134

Polarographic and spectroscopic studies of the effects of fluoroacetate/fluorocitrate on cells and mitochondria

Valeriy P. Zinchenko,1 Nikolay V. Goncharov,2 Vera V. Teplova,3 Vitaliy A. Kasymov,1 Olga I. Petrova,1 Alexey V. Berezhnov,1 Evgeniy V. Senchenkov,2 Igor V. Mindukshev,4 Richard O. Jenkins,5,6 and Andrey S. Radilov2

1Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russia
2Research Institute of Hygiene, Occupational Pathology and Human Ecology, St-Petersburg, Russia
3Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia
4I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St-Petersburg, Russia
5School of Allied Health Sciences, De Montfort University, Leicester, UK
6School of Allied Health Sciences, De Montfort University, Leicester, LE1 9BH, UK

Copyright © 2007 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Experiments were performed with rat liver mitochondria, Ehrlich ascite tumor cells (EATC) and cardiomyocytes, exposed to fluoroacetate (FA) or fluorocitrate (FC) in vitro. The effects of FA developed at much higher concentrations in comparison with FC and was dependent upon respiratory substrates: with pyruvate, FA induced a slow oxidation of pyridine nucleotides (NAD(P)H) and inhibition of respiration. NAD(P)H oxidation was prevented by incubation of mitochondria with cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore. Studies of the NAD(P)H level and calcium response generated in EATC under activation with ATP via the metabotropic P2Y receptor, revealed a loss of NAD(P)H from mitochondria resulting in a shift in the balance of mitochondrial and cytosolic NAD(P)H on exposure to FA. An increase of cytosolic [Ca2+] was observed in the cell lines exposed to FA and is explained by activation of plasma membrane calcium channels; this mechanism could have an impact on amplitude and rate of Ca2+ waves in cardiomyocytes, and cause the hypersensitivity of platelets reported on earlier. Highlighting the reciprocal relationship between intracellular NAD(P)H and calcium balance, we discuss metabolic pathway modulation in the context of development of an effective therapy for FA poisoning.