Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats

J Cancer Res Ther. 2014 Apr-Jun;10(2):274-8. doi: 10.4103/0973-1482.136557.

Abstract

Objectives: This work is aimed on the study of doxorubicin cardiotoxicity and hepatotoxicity in rats and the evaluation of protective effect of trimetazidine administrated concomitantly with doxorubicin for 3 days.

Materials and methods: Male Wistar rats used were subjected to different types of treatment (3 days); A: Control, B: Doxorubicin treatment and C: Trimetazidine and doxorubicin treatment. After sacrifice, tissular distribution of doxorubicin, cardiac scintigraphy, histological examination of the myocardium, and evaluation of liver function were assessed.

Results: Obtained results show that doxorubicin has a high affinity to tissues especially the heart. It causes hepatotoxicity and cardiotoxicity marked by a significant increase of aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) levels and drop of the left ventricular ejection fraction (EF LV ) by scintigraphy. Histological examination showed general alteration of myocardium structure. Concomitant administration of trimetazidine attenuates significantly the cardiotoxicity and hepatotoxity induced by doxorubicin.

Conclusion: We have evaluated the protective effect of trimetazidine on an animal model of doxorubicin-induced cardiotoxicity and hepatotoxicity. The evaluation of these effects were assessed by several means; tissular distribution of doxorubicin, histological examination, assessment of liver function, and EF LV by scintigraphy that characterizes the originality of this study.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / toxicity*
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Aspartate Aminotransferases / blood
  • Chemical and Drug Induced Liver Injury* / blood
  • Chemical and Drug Induced Liver Injury* / prevention & control
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / toxicity*
  • Drug Screening Assays, Antitumor
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Rats, Wistar
  • Stroke Volume / drug effects
  • Tissue Distribution
  • Trimetazidine / pharmacology*
  • Trimetazidine / therapeutic use
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / chemically induced*
  • Ventricular Dysfunction, Left / prevention & control

Substances

  • Antibiotics, Antineoplastic
  • Antioxidants
  • Doxorubicin
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Trimetazidine