Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats

J Biochem Mol Toxicol. 2018 Feb;32(2). doi: 10.1002/jbt.22030. Epub 2018 Jan 5.

Abstract

Doxorubicin (DXR) is a highly effective drug for chemotherapy. However, cardiotoxicity reduces its clinical utility in humans. The present study aimed to assess the ameliorative effect of curcumin against DXR-induced cardiotoxicity in rats. Rats were subjected to oral treatment of curcumin (100 and 200 mg/kg body weight) for 7 days. Cardiotoxicity was induced by single intraperitoneal injection of DXR (40 mg/kg body weight) on the 5th day and the rats sacrificed on 8th day. Curcumin ameliorated DXR-induced lipid peroxidation, glutathione depletion, decrease in antioxidant (superoxide dismutase, catalase, and glutathione peroxidase) enzyme activities, and cardiac toxicity markers (CK-MB, LDH, and cTn-I). Curcumin also attenuated activities of Caspase-3, cyclooxygenase-2, inducible nitric oxide synthase, and levels of nuclear factor kappa-B, tumor necrosis factor-α, and interleukin-1β, and cardiac tissue damages that were induced by DXR. Moreover, curcumin decreased the expression of 8-OHdG and 3,3'-dityrosine. This study demonstrated that curcumin has a multi-cardioprotective effect due to its antioxidant, anti-inflammatory, and antiapoptotic properties.

Keywords: apoptosis; cardiotoxicity; curcumin; doxorubicin; inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antibiotics, Antineoplastic / adverse effects
  • Antioxidants / administration & dosage
  • Antioxidants / adverse effects
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects*
  • Biomarkers / metabolism
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / therapeutic use*
  • Cardiotoxicity / immunology
  • Cardiotoxicity / metabolism
  • Cardiotoxicity / pathology
  • Cardiotoxicity / prevention & control*
  • Curcumin / administration & dosage
  • Curcumin / adverse effects
  • Curcumin / therapeutic use*
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / adverse effects
  • Glutathione / metabolism
  • Heart Ventricles / drug effects*
  • Heart Ventricles / immunology
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibiotics, Antineoplastic
  • Antioxidants
  • Biomarkers
  • Cardiotonic Agents
  • Doxorubicin
  • Glutathione
  • Curcumin