Department of Cardiology, Gülhane Research and Education Hospital, Ankara, Turkey.
Department of Physiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Amino Acids. 2019 Nov;51(10-12):1649-1655. doi: 10.1007/s00726-019-02801-7. Epub 2019 Oct 31.
Doxorubicin (DOXO) may cause serious cardiotoxic effects that limit its use as an antineoplastic agent. We aimed to evaluate the protective role of taurine (TAU), a beta amino acid with antioxidant activity, against DOXO-induced cardiotoxicity in a rat model. Thirty-one male Sprague-Dawley rats (300-400 g) were randomized into four groups: control (n = 7, intraperitoneal [ip] saline for 14 days), TAU (n = 8, 150 mg/kg body weight TAU ip for 14 days), DOXO (n = 8, 25 mg/kg body weight DOXO ip on 12th, 13th, and 14th days), and DOXO + TAU (n = 8, TAU for 14 days and DOXO on 12th, 13th, and 14th days). The left ventricular functions were evaluated on 15th day by echocardiography. The heart tissues were then excised for histological evaluation. In DOXO group, left ventricular ejection fraction (LVEF), fractional shortening (FS), and mitral lateral annulus (s') velocity were significantly lower, and the left ventricular end-diastolic and end-systolic diameters (LVEDD, LVESD) were significantly higher than control group (p < 0.05), indicating a significant deterioration in left ventricular functions. However, in comparison to DOXO group, LVESD, LVEDD, LVEF, FS, and s' were significantly improved in DOXO + TAU group (p < 0.05). On histological evaluation, contrary to the normal cellular structure of cardiomyocytes in control and TAU groups, DOXO group showed increased nuclear or cytoplasmic changes and infiltrative cell proliferation (p < 0.001), which were remarkably reduced in DOXO + TAU group (p < 0.001). TAU treatment has a protective effect against DOXO-induced cardiotoxicity on echocardiographical and histological evaluation. For common use of TAU to prevent DOXO-induced cardiotoxicity, our findings should be confirmed by clinical studies.
多柔比星(DOXO)可能会导致严重的心脏毒性作用,从而限制其作为抗肿瘤药物的使用。我们旨在评估牛磺酸(TAU)的保护作用,TAU 是一种具有抗氧化活性的β氨基酸,可防止多柔比星诱导的大鼠模型中的心脏毒性。31 只雄性 Sprague-Dawley 大鼠(300-400 克)被随机分为四组:对照组(n=7,腹腔内[ip]生理盐水 14 天)、TAU 组(n=8,150mg/kg 体重 TAU ip 14 天)、DOXO 组(n=8,第 12、13 和 14 天腹腔内 25mg/kg 体重 DOXO)和 DOXO+TAU 组(n=8,14 天 TAU 和第 12、13 和 14 天 DOXO)。第 15 天通过超声心动图评估左心室功能。然后取出心脏组织进行组织学评估。在 DOXO 组中,左心室射血分数(LVEF)、缩短分数(FS)和二尖瓣外侧环(s')速度显着降低,左心室舒张末期和收缩末期直径(LVEDD,LVESD)显着高于对照组(p<0.05),表明左心室功能显着恶化。然而,与 DOXO 组相比,DOXO+TAU 组的 LVESD、LVEDD、LVEF、FS 和 s'显着改善(p<0.05)。在组织学评估中,与对照组和 TAU 组的心肌细胞正常细胞结构相反,DOXO 组显示出增加的核或细胞质变化和浸润性细胞增殖(p<0.001),而 DOXO+TAU 组则显着减少(p<0.001)。TAU 治疗对超声心动图和组织学评估具有预防 DOXO 诱导的心脏毒性的作用。为了将 TAU 常规用于预防 DOXO 诱导的心脏毒性,我们的发现应通过临床研究得到证实。