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J Cancer Res Ther ; 10(2): 274-8, 2014.
Article in English | MEDLINE | ID: mdl-25022377

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.


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