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
- О.О. Bogomolez Institute of Physiology National Academy
of Science of Ukraine, Kyiv;
- 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
- Valvere V, Іnhvatsabaya L, Nu Chau de G. Comparing score of anticancer antibiotics adriamycin and farmorubicin cardiotoxicity. Cardiology.1989; 29 (9): 64-6. [Russian]
- Kovalenko V, Kalinkin N, Vatutin N. Сytostatics heart injuri. Donetsk: UkrNTEK. 2002; 350. [Russian]
- 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.
CrossRef
- 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]
- 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.
- Gille L, Nohl H. Analyses of the molecular mechanism of adriamycin-induced cardiotoxicity. Free Radic Biol Med. 1997; 23:775-82.
CrossRef
- 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.
- Srivastav G and Mehta JL. Currying the heart: curcumin and cardioprotection. J Cardiovasc Pharmacol. 2009; 14:22-7.
CrossRef
- Ströfer, M., Jelkmann, W. & Depping, R. Curcumin Decreases Survival of Hep3B Liver and MCF-7 Breast Cancer Cells. Strahlenther Onkol (2011) 187: 393–400.
- 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.
CrossRef
- 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.
CrossRef
- Perrone D, Ardito F, et al. Biological and therapeutic activities, and anticancer properties of curcumin. Exp Ther Med. 2015 Nov; 10(5):1615-23.
- 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.
- Chance B, Williams G. The respiratory chain and oxidative phosphorylation. Adv Enzymol. 1956; 17:65-134.
CrossRef
- Estabrook RW. Mitochondrial respiratory control and the polarographic measurement of ADP:Oratios. Methods Enzymol. 1967; 10:41-7.
CrossRef
- Lowry O, Rosebrough N, Fazz A, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem, 1951; 193(1):265-75.
- 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.
- Stalnaya ID, Garishvili TG. Method of determination of malondialdehyde using thiobarbituric acid. Modern Methods in Вiochem. 1977; 66-8. [Russian].
- Huwiler M, Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase/H2O2/iodide system. Eur J Biochem. 1984; 141: 69-74.
CrossRef
- 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.
- Koroljuk M, Ivanov L, Mayorov I, Tokarev V. Method for determination of catalase activity. LabBusiness. 1988; 1:16-9. [Russian].
- 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.
CrossRef
- Menshchikova E, Zenkov N. Antioxidants and inhibitors of radical oxidation processes. Adv Mol Biol 1993; 113(4):442-53.
- 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
|