title: Cardioprotective effect of grape-seed proanthocyanidins on doxorubicin-induced cardiac toxicity in rats.
abstract: BACKGROUND
  Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer agent. However, its use is limited due to its cardiotoxicity which is mainly attributed to accumulation of reactive oxygen species.
  
  
  OBJECTIVE
  This study was conducted to assess whether the antioxidant, proanthocyanidins (Pro) can ameliorate Dox-induced cardiotoxicity in rats.
  
  
  METHODS
  Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Pro (70 mg/kg, orally) once daily for 10 days. Group III received doxorubicin 15 mg/kg i.p. as a single dose on the 7th day and Group IV animals were treated with Pro once daily for 10 days and Dox on the 7th day. The parameters of study were serum biomarkers, cardiac tissue antioxidant status, ECG, and effect on aconitine-induced cardiotoxicity.
  
  
  RESULTS
  Cardiac toxicity of doxorubicin was manifested as a significant increase in heart rate, elevation of the ST segment, prolongation of the QT interval and an increase in T wave amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a significant decrease in the aconitine dose producing ventricular tachycardia (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and normalized the aconitine dose producing VT. The toxicity of Dox was also confirmed biochemically by significant elevation of serum CK-MB and LDH activities as well as myocardial MDA and GSH contents and decrease in serum catalase and myocardial SOD activities. Administration of Pro significantly suppressed these biochemical changes.
  
  
  CONCLUSIONS
  These results suggest that proanthocyanidins might be a potential cardioprotective agent against Dox-induced cardiotoxicity due to its antioxidant properties.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: El-Sayed M
authors.initials: el-SM
authors.lastname: Ammar
authors.forename: Shehta A
authors.initials: SA
authors.lastname: Said
authors.forename: Sally L
authors.initials: SL
authors.lastname: El-Damarawy
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Suddek
mesh_terms: D000157:Aconitine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000975:Antioxidants / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D054715:Cardiotoxins / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004317:Doxorubicin / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D004351:Drug Resistance / Q000187:drug effects; D056604:Grape Seed Extract / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D044945:Proanthocyanidins / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013610:Tachycardia / Q000139:chemically induced / Q000517:prevention & control; D061585:Voltage-Gated Sodium Channel Agonists / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D054715:Cardiotoxins; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D061585:Voltage-Gated Sodium Channel Agonists; D004317:Doxorubicin; D000157:Aconitine