[EFFECT OF CURCUMIN ON MITOCHONDRIAL FUNCTION OF CARDIOMYOCYTES WITH DOXORUBICIN-INDUCED OXIDATIVE STRESS]

Fiziol Zh (1994). 2017;63(1):10-16. doi: 10.15407/fz63.01.010.
[Article in Ukrainian]

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 H(2)0(2) 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 H(2)0(2) 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 (V(3)) fell by 43.8%, the oxidation rate of the contingency of phosphorylation (V(3)/V(4)(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: V(3) raised by 25%, V(3)/V(4)(ATP)by 18% and ADP/O by 12% respectively.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cardiotonic Agents / pharmacology*
  • Catalase / metabolism
  • Curcumin / pharmacology*
  • Doxorubicin / antagonists & inhibitors*
  • Doxorubicin / pharmacology
  • Electron Transport Chain Complex Proteins / metabolism
  • Female
  • Hydrogen Peroxide / metabolism
  • Lipid Peroxidation / drug effects
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Necrosis / chemically induced
  • Necrosis / metabolism
  • Necrosis / pathology
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress / drug effects*
  • Primary Cell Culture
  • Rats
  • Rats, Inbred F344
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antioxidants
  • Cardiotonic Agents
  • Electron Transport Chain Complex Proteins
  • Thiobarbituric Acid Reactive Substances
  • Doxorubicin
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase
  • Curcumin