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Year : 2014  |  Volume : 10  |  Issue : 2  |  Page : 274-278

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

1 Service de Pharmacologie Clinique, Centre National de Pharmacovigilance; Unité d'Expérimentation Animale, Faculté de Médecine de Tunis, Tunis, Tunisia
2 Service de Pharmacologie Clinique, Centre National de Pharmacovigilance, Tunis, Tunisia
3 Service de Médecine Nucléaire, Hôpital Militaire de Tunis, Tunisia
4 Service d'Anatomie Pathologique, Hôpital Charles Nicolle de Tunis, Tunisia

Correspondence Address:
Issam Salouege
Centre National de Pharmacovigilance, 9 Rue Dr Zouhair Essafi-1006 Tunis
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.136557

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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.

Abstract in Chinese

阿霉素诱导的大鼠心脏毒性和肝毒性评价和保护 摘要 目的:这项工作的目的是研究曲美他嗪伴随阿霉素给药3天对阿霉素导致的大鼠心脏毒性和肝毒性的保护作用的评价研究。 材料与方法:雄性Wistar大鼠用于进行不同类型的治疗(3天);A:对照,B:阿霉素治疗C:曲美他嗪伴阿霉素治疗。观察阿霉素组织分布,心肌显像,心肌组织学检查,及肝功能情况。 结果:阿霉素具有高组织亲和性,尤其是心脏。阿霉素导致肝毒性和心脏毒性,表现为天冬氨酸(AST)及丙氨酸(ALT)水平增加显著,心肌显像左心室射血分数下降。组织学检查显示心肌细胞结构的变化。曲美他嗪联合用药显著减少阿霉素诱导的心脏毒性与肝毒性。 结论:本研究通过多种手段包括阿霉素组织分布,组织学检查,肝功能评估,心肌显像左心室射血分数,观察曲美他嗪对阿霉素诱导的心脏毒性和肝损伤动物模型的保护作用。 关键词:心肌显像,心脏毒性,阿霉素,肝毒性,曲美他嗪

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