title: Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de Pharmacologie Clinique, Centre National de Pharmacovigilance; Unité d'Expérimentation Animale, Faculté de Médecine de Tunis, Tunis, Tunisia.
authors.forename: Issam
authors.initials: I
authors.lastname: Salouege
authors.forename: Ridha
authors.initials: R
authors.lastname: Ben Ali
authors.forename: Dorra
authors.initials: D
authors.lastname: Ben Saïd
authors.forename: Noomen
authors.initials: N
authors.lastname: Elkadri
authors.forename: Nadia
authors.initials: N
authors.lastname: Kourda
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lakhal
authors.forename: Anis
authors.initials: A
authors.lastname: Klouz
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects; D014018:Tissue Distribution; D014292:Trimetazidine / Q000494:pharmacology* / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004317:Doxorubicin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D014292:Trimetazidine