[DOXORUBICIN-INDUCED ALTERATIONS IN PRO-AND ANTIOXIDANT BALANCE AND THEIR CORRECTION BY CURCUMIN IN THE NEONATAL RAT CARDIOMYOCYTES CULTURE]

Fiziol Zh (1994). 2015;61(5):90-8. doi: 10.15407/fz61.05.090.
[Article in Ukrainian]

Abstract

It was studied the effect of doxorubicin on the HIF system and the pro-antioxidant balance of neonatal cardiomyocytes as well as the possibility of the oxidative stress correcting using curcumin. It has been revealed that the expression of mRNA HIF-1α using doxorubicin at a dose of 0.5 μM was 2.9 ± 0.8 cu, so it decreased by 20% compared to control--3.6 ± 0.7 cu (P < 0.05). The level of expression of the HIF target gene PDK-1 also significantly decreased (4 times). During the incubation with doxorubicin, the number of live cells decreased by 50.4% relative to control. And after using doxorubicin and curcumin together, the percentage of dead cells decreased by 7,7 compared to doxorubicin only. Doxorubicin intoxication led to a significant increase in the secondary products of lipid peroxidation (TBARS) in cardiomyocytes by 3.6 times and hydrogen peroxide by 64%. Prolonged incubation with doxorubicin reduced the enzymatic activity of Mn-SOD by 32%, while catalase activity increased by 72% compared to control. Adding of curcumin to the cardiomyocyte cell culture contributed to increasing of the Mn-SOD activity by 14%, catalase--by 23%. The level of TBARS increased by 1,4 times compared with the control, and the level of H2O2 increased by 20%. The joint use of doxorubicin and curcumin resulted in a significant reduction of free radical oxidation unlike effect of doxorubicin per se. Specifically, there was lessening of TBARS and H2O2 (at 56.7 and 18.4% respectively), while decreasing of the catalase hyperactivation (19%) and rising of the Mn-SOD activity (35%).

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibiotics, Antineoplastic / toxicity*
  • Antioxidants / pharmacology*
  • Catalase / genetics
  • Catalase / metabolism
  • Curcumin / pharmacology*
  • Doxorubicin / antagonists & inhibitors
  • Doxorubicin / toxicity*
  • Gene Expression Regulation
  • Glutathione / metabolism
  • Hydrogen Peroxide / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lipid Peroxidation
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Oxidative Stress / drug effects
  • Primary Cell Culture
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Antioxidants
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • RNA, Messenger
  • Thiobarbituric Acid Reactive Substances
  • Doxorubicin
  • Hydrogen Peroxide
  • Catalase
  • Superoxide Dismutase
  • Protein Serine-Threonine Kinases
  • Glutathione
  • Curcumin