Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity

Environ Toxicol Pharmacol. 2013 Sep;36(2):347-357. doi: 10.1016/j.etap.2013.04.018. Epub 2013 May 10.

Abstract

The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

Keywords: Cannabidiol; Doxorubicin cardiotoxicity; Inflammation; Oxidative stress; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Calcium / metabolism
  • Cannabidiol / pharmacology*
  • Caspase 3 / metabolism
  • Creatine Kinase, MB Form / blood
  • Cytoprotection
  • Disease Models, Animal
  • Doxorubicin*
  • Fas Ligand Protein / metabolism
  • Glutathione / metabolism
  • Heart Diseases / blood
  • Heart Diseases / chemically induced
  • Heart Diseases / pathology
  • Heart Diseases / prevention & control*
  • Inflammation Mediators / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Selenium / metabolism
  • Signal Transduction / drug effects
  • Troponin T / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • Zinc / metabolism

Substances

  • Biomarkers
  • Fas Ligand Protein
  • Faslg protein, rat
  • Inflammation Mediators
  • NF-kappa B
  • Protective Agents
  • Troponin T
  • Tumor Necrosis Factor-alpha
  • Cannabidiol
  • Nitric Oxide
  • Malondialdehyde
  • Doxorubicin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Creatine Kinase, MB Form
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione
  • Selenium
  • Zinc
  • Calcium