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长期给予癸酸诺龙后家兔的心脏毒性。

Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

作者信息

Vasilaki Fotini, Tsitsimpikou Christina, Tsarouhas Konstantinos, Germanakis Ioannis, Tzardi Marias, Kavvalakis Matthaios, Ozcagli Eren, Kouretas Dimitrios, Tsatsakis Aristidis M

机构信息

Center of Toxicology Science & Research, Medical School, University of Crete, Heraklion, Crete, Greece.

Department of Dangerous Substances, Mixtures and Articles, Directorate of Energy, Industrial & Chemical Products, General Chemical State Laboratory of Greece, Athens, Greece.

出版信息

Toxicol Lett. 2016 Jan 22;241:143-51. doi: 10.1016/j.toxlet.2015.10.026. Epub 2015 Nov 2.

Abstract

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.

摘要

合成代谢雄激素类固醇的滥用与多种心血管并发症有关。我们研究的目的是利用超声心动图、组织学以及端粒酶活性、氧化应激和生化标志物监测,调查癸酸诺龙对幼兔可能产生的心血管影响。将14只兔子分为三个给药组和一个对照组。采用每周两次、为期六个月的给药方式,肌肉注射和皮下注射4mg/kg和10mg/kg的癸酸诺龙。随后有一个4个月的洗脱期。在高剂量组中观察到心脏组织的局灶性纤维化和炎性浸润。高剂量组中硫代巴比妥酸反应性物质(TBARS)水平显著升高,而过氧化氢酶活性降低。心肌性能指数(MPI)是超声心动图的主要指标,主要受兔子体内癸酸诺龙给药的影响。尽管收缩功能得以保留,但观察到的与MPI值扭曲相关的组织学病变表明,癸酸诺龙治疗导致增厚心肌的舒张功能受损。氧化应激累积,心脏组织中的端粒酶活性升高。皮下给药似乎对心血管系统更具危害性,因为在洗脱期氧化应激、端粒酶活性和生化标志物似乎并未恢复到正常水平。

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