乙酰左旋肉碱对大白鼠多柔比星心脏毒性的保护作用。

Protective Effect of Acetyl-L-Carnitine Against Doxorubicin-induced Cardiotoxicity in Wistar Albino Rats.

机构信息

Department of Pediatrics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

Department of Histology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.

出版信息

Arch Med Res. 2016 Oct;47(7):506-514. doi: 10.1016/j.arcmed.2016.11.008.

DOI:10.1016/j.arcmed.2016.11.008

PMID:28262191

Abstract

BACKGROUND AND AIMS

Anthracyclines are one of the most preferred agents in practical pediatric oncology despite their dose-dependent cardiotoxic effects. The aim of this study was to investigate whether or not acetyl-L-carnitine (ALCAR) has protective effects on doxorubicin (DOX)-induced cardiotoxicity.

METHODS

Wistar rats were divided into four groups; control, DOX, ALCAR and ALCAR+DOX. Rats in the first group were given saline on study days, whereas those in the second group were given a single dose of DOX on the 5 day and saline on the other days. Rats in the third group were given ALCAR and those in the fourth group were given ALCAR on study days but also given only a single dose of DOX on the fifth day of the study. Ejection fractions (EF) were measured by echocardiography before and after drug administration. Heart tissues were evaluated by light and electron microscopy. Apoptotic cells were determined with TUNEL and caspase-3 staining.

RESULTS

DOX significantly decreased the EF values, whereas ALCAR did not. Cardiac functions were higher in the ALCAR+DOX group when compared to the DOX group. DOX administration caused a cardiac injury not only functionally, but also structurally, whereas ALCAR prevented it.

CONCLUSIONS

ALCAR has a capacity of preventing DOX-induced cardiac injury at both functional and structural levels.

摘要

背景与目的

尽管蒽环类药物具有剂量依赖性的心脏毒性作用，但它仍是儿科肿瘤学中最常用的药物之一。本研究旨在探讨乙酰左旋肉碱（ALCAR）是否对多柔比星（DOX）诱导的心脏毒性具有保护作用。

方法

Wistar 大鼠分为四组：对照组、DOX 组、ALCAR 组和 ALCAR+DOX 组。第一组大鼠在研究期间给予生理盐水，第二组大鼠在第 5 天给予单剂量 DOX，其余时间给予生理盐水。第三组大鼠给予 ALCAR，第四组大鼠在研究期间给予 ALCAR，但在研究第 5 天也给予单剂量 DOX。给药前后通过超声心动图测量射血分数（EF）。通过光镜和电镜观察心脏组织。用 TUNEL 和 caspase-3 染色法检测凋亡细胞。