Coenzyme Q10 Cardioprotective Effects Against Doxorubicin-Induced Cardiotoxicity in Wistar Rat

Cardiovasc Toxicol. 2020 Jun;20(3):222-234. doi: 10.1007/s12012-019-09547-4.

Abstract

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity.

Keywords: Cardiotoxic effect; Electrocardiogram; Oxidative stress; Ubiquinol.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Cardiomyopathies / prevention & control*
  • Cardiotoxicity
  • Disease Models, Animal
  • Doxorubicin*
  • Lipid Peroxidation / drug effects
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / ultrastructure
  • Oxidative Stress / drug effects*
  • Rats, Wistar
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology

Substances

  • Antioxidants
  • Ubiquinone
  • Doxorubicin
  • coenzyme Q10