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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(1): 10-16


EFFECT OF CURCUMIN ON MITOCHONDRIAL FUNCTION OF CARDIOMYOCYTES WITH DOXORUBICININDUCED OXIDATIVE STRESS

O. Linnik 1, O. Gonchar 1, V. Nosar1, T. Drevytska1, O. Kovalyov2, I. Mankovska1

  1. О.О. Bogomolez Institute of Physiology National Academy of Science of Ukraine, Kyiv;
  2. National Aviation University, Kyiv.
DOI: https://doi.org/10.15407/fz63.01.010

Abstract

We studied the effect of curcumin on the cardiomyocytes viability, processes of oxidative phosphorylation in the mitochondria of cardiomyocytes, their pro- and antioxidant balance in doxorubicin-induced oxidative stress. It has been revealed that administration of doxorubicin to rats led to a significant increase in the secondary products of lipid peroxidation (TBARS) in mitochondria by 21 and H2O2 by 76%, reduction of the enzymatic activity of mitochondrial Mn-SOD by 14% and intensified catalase activity by 80% compared with the control. After combined use of doxorubicin and curcumin the content of TBARS and H2O2 increased by 14 and 26%, respectively, the enzymatic activity of catalase decreased by 28%, and mitochondrial Mn-SOD activity intensified by 9%. During the incubation with doxorubicin, the number of live cells decreased by 30.4% and the number of necrotic cells increased by 30.4% relative to control. Coadministration of doxorubicin and curcumin led to augmented cell viability by 8%, while the number of necrotic cells reduced by 8% compared with the use of doxorubicin only. In assessing the parameters of mitochondrial respiration in rats that received injections of doxorubicin active breathing index (V3) fell by 43.8%, the oxidation rate of the contingency of phosphorylation (V3/V4 ATP) decreased by 47% and phosphorylation efficiency index (ADP/O) also declined by 31.7% respectively compared with the control. The combined use of doxorubicin and curcumin improved the indicators of mitochondrial respiration compared to using only doxorubicin: V3 raised by 25%, V3/V4 ATP by 18% and ADP/O by 12% respectively.

Keywords: mitochondria; oxidative stress; doxorubicin; curcumin.

References

  1. Valvere V, Іnhvatsabaya L, Nu Chau de G. Comparing score of anticancer antibiotics adriamycin and farmorubicin cardiotoxicity. Cardiology.1989; 29 (9): 64-6. [Russian]
  2. Kovalenko V, Kalinkin N, Vatutin N. Сytostatics heart injuri. Donetsk: UkrNTEK. 2002; 350. [Russian]
  3. Minnoti G, Mancuso C, Frustac A et al. Paradoxical inhibition of cardiac lipid peroxidation in cancer patients treated with doxorubicin Pharmacologic and molecular reappraisal of anthracycline cardiotoxicity. J Clin invest. 1996; 98:650-61.
  4. CrossRef
  5. Baraboi V, Sutkovoy D. The oxidation-antioxidant homeostasis in normal and pathological conditions. Ed. Acad. Ukrainian Academy of Medical Sciences Y Zozulya. K.: Chernobylinterinform. 1997; 420. [Russian]
  6. Eidenschink AB, Schroter G, Muller Welhrich S et al. Myocardial high-energy phosphate metabolism is altered after treatment with anthracicline in children. Cardiol. Young. 2000; 10:610-17.
  7. Gille L, Nohl H. Analyses of the molecular mechanism of adriamycin-induced cardiotoxicity. Free Radic Biol Med. 1997; 23:775-82.
  8. CrossRef
  9. Eidenschink AB, Schroter G, Muller Welhrich S et al. Myocardial high-energy phosphate metabolism is altered after treatment with anthracycline in children. Cardiol. Young. 2000; 10:610-17.
  10. Srivastav G and Mehta JL. Currying the heart: curcumin and cardioprotection. J Cardiovasc Pharmacol. 2009; 14:22-7.
  11. CrossRef
  12. Ströfer, M., Jelkmann, W. & Depping, R. Curcumin Decreases Survival of Hep3B Liver and MCF-7 Breast Cancer Cells. Strahlenther Onkol (2011) 187: 393–400.
  13. Swamy AV, Gulliaya S, Thippeswamy A, et al. Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian J Pharmacol. 2012; 44:73-7.
  14. CrossRef
  15. Mohamad RH, El-Bastawesy AM, Zekry ZK et al. The role of Curcuma longa against doxorubicin (adriamycin)- induced toxicity in rats. J Med Food. 2009; 12:394-402.
  16. CrossRef
  17. Perrone D, Ardito F, et al. Biological and therapeutic activities, and anticancer properties of curcumin. Exp Ther Med. 2015 Nov; 10(5):1615-23.
  18. Kondrashova MN, Fedotcheva NI, Saakyan IR et al. Preservation of native properties of mitochondria in rat liver homogenate. Mitochondrion. 2001 Oct; 1(3):249-67.
  19. Chance B, Williams G. The respiratory chain and oxidative phosphorylation. Adv Enzymol. 1956; 17:65-134.
  20. CrossRef
  21. Estabrook RW. Mitochondrial respiratory control and the polarographic measurement of ADP:Oratios. Methods Enzymol. 1967; 10:41-7.
  22. CrossRef
  23. Lowry O, Rosebrough N, Fazz A, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem, 1951; 193(1):265-75.
  24. Surova O, Nagibin V, Tumanovskaya L, Dosenko V, Moibenko A. Effect of a low dose of proteasome inhibitor on cell death and gene expression in neonatal rat cardiomyocyte cultures exposed to anoxia-reoxygenation. Exp Clin Cardiol. 2009; 14(2):57-61.
  25. Stalnaya ID, Garishvili TG. Method of determination of malondialdehyde using thiobarbituric acid. Modern Methods in Вiochem. 1977; 66-8. [Russian].
  26. Huwiler M, Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase/H2O2/iodide system. Eur J Biochem. 1984; 141: 69-74.
  27. CrossRef
  28. Misra H, Fridovich I. The role of superoxide anion in the autoxidation of Epinephrine and a simple assay superoxide dismutase. J Biol Chem. 1972; 247(10):3170-5.
  29. Koroljuk M, Ivanov L, Mayorov I, Tokarev V. Method for determination of catalase activity. LabBusiness. 1988; 1:16-9. [Russian].
  30. Wang J, Ma J, Giffard R. Overexpression of copper/zinc superoxidedismutase decreases ischemia-like astrocyte injury. Free Radic Biol Med 2005;38(8):1112-8.
  31. CrossRef
  32. Menshchikova E, Zenkov N. Antioxidants and inhibitors of radical oxidation processes. Adv Mol Biol 1993; 113(4):442-53.
  33. Linnik O, Drevytska T, Gonchar O, Chornyy S, Kovalyov O, Mankovska I. Pro–antioxidant doxorubicin caused imbalance and its correction by curcumin in the neonatal rat cardiomyocytes culture. Fiziol Zh. 2015; 61(5):90-8. [Ukrainian].CrossRef  PMID: 26845849

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